Duration of skin photosensitivity and incidence of photosensitivity reactions after administration of verteporfin.

PubMed

Houle, Jean-Marie; Strong, H Andrew

2002-12-01

Verteporfin (Visudyne, Novartis AG) is a light-activated drug that reduces the risk of vision loss in patients with certain types of choroidal neovascularization (CNV). Because photosensitivity can occur with photosensitizers, it is important for ophthalmologists providing verteporfin therapy to understand its time course and duration, as well as the incidence of photosensitivity reactions. Data were obtained from three sources: 1) the time course of skin photosensitivity in 17 volunteers by measuring erythema/edema over time after verteporfin, using red light exposure; 2) the duration of skin photosensitivity in 30 patients with skin cancer by exposing skin to simulated solar light and calculating the daily minimal erythematous dose; and 3) the incidences of photosensitivity reactions as recorded in three phase III trials in patients with CNV secondary to age-related macular degeneration or pathologic myopia who received the regimen of verteporfin therapy currently approved by regulatory authorities (infusion of 6 mg/m(2) body surface area). 1) Skin photosensitivity was high at the first timepoint of 1.5 hours after dosing and decreased rapidly thereafter; 2) the duration of skin photosensitivity was dose dependent, ranging from 2.0 to 6.7 days at 6 to 20 mg/m(2), respectively (mean of 2 days at a dose of 6 mg/m(2)); and 3) photosensitivity reactions occurred in only 2.2% of patients in the phase III trials, including two severe events, one secondary to extravasation. All treatment-related reactions in the phase III trials occurred within the first 2 days after dosing, with the exception of two mild reactions and one moderate reaction that occurred 3 days after treatment. Verteporfin is associated with short-lived photosensitivity and a low incidence of photosensitivity reactions in clinical trials, most of which could probably have been avoided by adherence to protocol instructions for skin protection.

An unusual photosensitizer: dyad of eosin-tris(2,2'-bipyridine)Ru(II).

PubMed

Jing, Bingwen; Zhang, Manhua; Shen, Tao

2003-10-02

[structure: see text] A dyad of eosin and tris(2,2'-bipyridine)Ru(II) was prepared, and its photophysical properties were investigated. The photosensitization of eosin is greatly enhanced by introduction of tris(2,2'-bipyridine)Ru(II), which is verified via photooxygenation of anthracene derivatives. The electron-transfer mechanism of photosensitization is also discussed.

Study of photosensitization reaction progress in a 96 well plate with photosensitizer rich condition using Talaporfin sodium

NASA Astrophysics Data System (ADS)

Ogawa, Emiyu; Takahashi, Mei; Arai, Tsunenori

2013-02-01

To quantitatively investigate photosensitization reaction in vitro against myocardial cells with photosensitizer rich condition in solution using Talaporfin sodium in the well of a 96 well plate, we studied photosensitization reaction progress in this well. We have proposed non-thermal conduction block of myocardium tissue using the photosensitization reaction with laser irradiation shortly after Talaporfin sodium injection. In above situation, the photosensitizer is located outside the myocardial cells in high concentration. To understand interaction of the photosensitization reaction in which the photosensitizer distributes outside cells, the photosensitization reaction progress in the well was studied. Talaporfin sodium (799.69 MW) solution and a 663 nm diode laser were used. The photosensitizer solution concentrations of 12.5-37.5 μM were employed. The photosensitizer fluorescence with 0.29 W/cm2 in irradiance, which was optimized in previous cell death study, was measured during the laser irradiation until 40 J/cm2. The photosensitizer solution absorbance and dissolved oxygen pressure after the laser irradiation were also measured. We found that the photosensitization reaction progress had 2 distinctive phases of different reaction rate: rapid photosensitization reaction consuming dissolved oxygen and gentle photosensitization reaction with oxygen diffusion from the solution-air boundary. The dissolved oxygen pressure and photosensitizer solution absorbance were 30% and 80% of the initial values after the laser irradiation, respectively. Therefore, oxygen was rate-controlling factor of the photosensitization reaction in the well with the photosensitizer rich condition. In the oxygen diffusion phase, the oxygen pressure was maintained around 40 mmHg until the laser irradiation of 40 J/cm2 and it is similar to that of myocardium tissue in vivo. We think that our 96 well plate in vitro system may simulate PDT in myocardial tissue with photosensitization reaction

Photosensitized inactivation of infectious blood-borne human parasites

NASA Astrophysics Data System (ADS)

Judy, Millard M.; Sogandares-Bernal, Franklin M.; Matthews, James Lester

1995-05-01

Blood-borne viruses and protozoan parasites that are infectious to humans pose risk world-wide of infection transmission through blood and blood product transfusion. Blood-borne infectious viruses include human immunodeficiency virus (HIV-I), which causes AIDS; hepatitis C virus, which can cause chronic hepatitis; and cytomegalovirus, which can be dangerous to immunocompromised patients, e.g., the newborn, transplant recipients, and AIDS patients. Infectious blood-borne protozoan parasites include Trypanosoma cruzi, which causes Chagas' disease, endemic throughout Central and South America; the Trypanosoma species causing African sleeping sickness endemic in Central Africa; and Plasmodium falciparum, which causes malignant and increasingly drug- resistant human malaria prevalent throughout the tropics. Some researchers have focused on using photosensitizers to inactivate HIV-I and other viruses in whole blood, packed red cells, and platelet concentrates without compromising blood product function. Our group previously has reported photosensitized in vitro inactivation of P. falciparum and the mouse malaria organism Plasmodium berghei in whole blood using hematoporphyrin derivative (HPD) and of T. cruzi using benzoporphyrin derivatives BPDMA and BPDDA, dihematoporphyrin ether (DHE), and hydroxyethylvinyldeuteroporphyrin (HEVD). These results suggest that continued investigation is warranted to evaluate the potential for photosensitized inactivation of blood-borne parasites in blood banking.

Discovery and Development of Natural Products and their Derivatives as Photosensitizers for Photodynamic Therapy.

PubMed

Xiao, Qicai; Wu, Juan; Pang, Xin; Jiang, Yue; Wang, Pan; Leung, Albert W; Gao, Liqian; Jiang, Sheng; Xu, Chuanshan

2018-01-01

Photodynamic therapy (PDT) has been developed as an alternative modality for the management of neoplastic and nonneoplastic diseases. It is a minimally invasive treatment that involves the interaction of a non-toxic photosensitizer (PS), light and molecular oxygen to generate reactive oxygen species (ROS), resulting in the destruction of unwanted cells and tissues. Discovery and development of new PSs with optimized properties are much crucial for achieving a desirable therapeutic efficacy. This review describes the photochemical and photobiological mechanisms of PDT, and outlines the recent progress in discovery and development of natural products and their derivatives as phototherapeutic drugs. The potential limitations and future perspectives of PDT in clinical application are also presented and discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Glucose-functionalized amino-OPEs as biocompatible photosensitizers in PDT.

PubMed

Deni, Elisa; Zamarrón, Alicia; Bonaccorsi, Paola; Carmen Carreño, M; Juarranz, Ángeles; Puntoriero, Fausto; Sciortino, Maria Teresa; Ribagorda, María; Barattucci, Anna

2016-03-23

Photodynamic therapy (PDT) is a minimally invasive procedure that can provide a selective eradication of neoplastic diseases by the combined effect of a photosensitizer, light and oxygen. New amino oligo(phenylene-ethynylene)s (OPEs), bearing hydrophilic glucoside terminations, have been prepared, characterized and tested as photosensitizers in PDT. The effectiveness of these compounds in combination with UVA light has been checked on two tumor cell lines (HEp-2 and HeLa cells, derived from a larynx carcinoma and a cervical carcinoma, respectively). The compounds triggered a mitotic blockage that led to the cell death, being the effect active up to 3 μm concentration. The photophysical properties of OPEs, such as high quantum yield, stability, singlet oxygen production, biocompatibility, easy cell-internalization and very good response even at low concentration, make them promising photosensitizers in the application of PDT. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Smart photovoltaics based on dye-sensitized solar cells using photochromic spiropyran derivatives as photosensitizers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Shengbo; Ting, Hungkit; Ma, Yingzhuang

2015-05-15

In this paper, smart photovoltaic (SPV) devices, integrating both functions of solar cells and smart windows, was fabricated based on dye-sensitized solar cells using photochromic spiropyran derivatives SIBT as photosensitizers. SPV devices have self-regulated power conversion efficiency (PCE) and light transmission responding to the incident spectra due to the photoisomerization of SIBT. SIBT isomerize from closed-ring form to open-ring form under UV illumination, accompanied with enhanced visible light absorption and electron delocalization. Therefore, increased PCE and absorption in SPV devices were observed under UV treatment and the devices can be restored gradually to the initial status when kept in dark.more » The SPV devices have self-regulation of PCE and sunlight transmission responding to the changing sun spectra in different times of a day, providing a proper energy usage and a better sun-shading.« less

Photosensitive disorders in HIV

PubMed Central

2017-01-01

Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible. PMID:29568622

Photosensitive disorders in HIV.

PubMed

Koch, Karen

2017-01-01

Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible.

The nature, fabrication, and applications of photosensitive, bulk, germano-silicate glass

NASA Astrophysics Data System (ADS)

Heaney, Alan Douglas

2000-08-01

The photosensitive nature of germano-silicate glass is widely used to create fiber-optic devices. This thesis examines the cause of photosensitivity in germano- silicate glass. The results of this research elucidate the role that germanium oxygen deficient defects play in the photosensitivity of hydrogen-loaded, germano-silicate glass. We find that defects are not vital to the photosensitivity of hydrogen-loaded, germano-silicate glass but they do enhance the effect. Quantitative measurements show that germanium oxygen deficient defects promote the formation of OH, GeH, and GeH2 when hydrogen-loaded, germano-silicate glass is exposed to ultraviolet light. A sol-gel process for fabricating germano-silicate glass in bulk samples has been developed. The sol-gel process produces high-quality, germano-silicate glass which can be tailored to contain defects or be relatively free of defects. Control over the glass defect concentration allows us to use sol-gel derived glass for comparative studies of the photosensitive process and for device applications. The unique properties of germano-silicate glass make it a likely choice for use in optical applications. To prove the feasibility of bulk devices, chirped-pulse amplification is demonstrated using gratings written in bulk germano-silicate glass.

Organic photosensitive devices

DOEpatents

Rand, Barry P; Forrest, Stephen R

2013-11-26

The present invention generally relates to organic photosensitive optoelectronic devices. More specifically, it is directed to organic photosensitive optoelectronic devices having a photoactive organic region containing encapsulated nanoparticles that exhibit plasmon resonances. An enhancement of the incident optical field is achieved via surface plasmon polariton resonances. This enhancement increases the absorption of incident light, leading to a more efficient device.

Inverted organic photosensitive devices

DOEpatents

Forrest, Stephen R.; Bailey-Salzman, Rhonda F.

2016-12-06

The present disclosure relates to organic photosensitive optoelectronic devices grown in an inverted manner. An inverted organic photosensitive optoelectronic device of the present disclosure comprises a reflective electrode, an organic donor-acceptor heterojunction over the reflective electrode, and a transparent electrode on top of the donor-acceptor heterojunction.

In vitro Cellular Uptake and Dimerization of Signal Transducer and Activator of Transcription-3 (STAT3) Identify the Photosensitizing and Imaging-Potential of Isomeric Photosensitizers Derived from Chlorophyll-a and Bacteriochlorophyll-a

PubMed Central

Srivatsan, Avinash; Wang, Yanfang; Joshi, Penny; Sajjad, Munawwar; Chen, Yihui; Liu, Chao; Thankppan, Krishnakumar; Missert, Joseph R.; Tracy, Erin; Morgan, Janet; Rigual, Nestor; Baumann, Heinz; Pandey, Ravindra K.

2011-01-01

Among the photosensitizers investigated, both ring-D and ring-B reduced chlorins containing the m-iodobenzyloxyethyl group at position-3 and a carboxylic acid functionality at position-172 showed highest uptake by tumor cells and light-dependent photo reaction that correlated with maximal tumor-imaging [positron emission tomography (PET) and fluorescence] and long-term photodynamic therapy (PDT) efficacy in BALB/c mice bearing Colon26 tumors. However, among the ring-D reduced compounds, the isomer containing 1′-m-iobenzyloxyethyl group at position-3 was more effective than the corresponding 8-(1′-m-iodobenzyloxyethyl) derivative. All photosensitizers showed maximum uptake by tumor tissue 24h after injection and the tumors exposed with light at low fluence and fluence rates (128 J/cm2, 14 mW/cm2) produced significantly enhanced tumor eradication than those exposed at higher fluence and fluence rate (135 J/cm,2 75mW/cm2). Interestingly, dose-dependent cellular uptake of the compounds and light-dependent STAT3 dimerization have emerged as sensitive rapid indicators for PDT efficacy in vitro and in vivo and could be used as in vitro/in vivo biomarkers for evaluating and optimizing the in vivo treatment parameters of the existing and new PDT candidates. PMID:21842893

Organic photosensitive optoelectronic device having a phenanthroline exciton blocking layer

DOEpatents

Thompson, Mark E [Anaheim Hills, CA; Li, Jian [Los Angeles, CA; Forrest, Stephen [Princeton, NJ; Rand, Barry [Princeton, NJ

2011-02-22

An organic photosensitive optoelectronic device, having an anode, a cathode, and an organic blocking layer between the anode and the cathode is described, wherein the blocking layer comprises a phenanthroline derivative, and at least partially blocks at least one of excitons, electrons, and holes.

Photosensitized Formation of Secondary Organic Aerosols above the Air/Water Interface

PubMed Central

2016-01-01

In this study, we evaluated photosensitized chemistry at the air–sea interface as a source of secondary organic aerosols (SOA). Our results show that, in addition to biogenic emissions, abiotic processes could also be important in the marine boundary layer. Photosensitized production of marine secondary organic aerosol was studied in a custom-built multiphase atmospheric simulation chamber. The experimental chamber contained water, humic acid (1–10 mg L–1) as a proxy for dissolved organic matter, and nonanoic acid (0.1–10 mM), a fatty acid proxy which formed an organic film at the air–water interface. Dark secondary reaction with ozone after illumination resulted in SOA particle concentrations in excess of 1000 cm–3, illustrating the production of unsaturated compounds by chemical reactions at the air–water interface. SOA numbers via photosensitization alone and in the absence of ozone did not exceed background levels. From these results, we derived a dependence of SOA numbers on nonanoic acid surface coverage and dissolved organic matter concentration. We present a discussion on the potential role of the air–sea interface in the production of atmospheric organic aerosol from photosensitized origins. PMID:27434860

Retrospective analysis of drug photosensitivity in Norway

NASA Astrophysics Data System (ADS)

Selvaag, Edgar

1999-02-01

Reports on adverse drug reactions, as they were recorded at the Norwegian Medicines Control Authority beginning in the year 1970 up to 1994 were analyzed especially with regard to cutaneous reactions and photosensitivity reactions. During the time period, almost 13.000 side effects were reported. Out of these 799 reports involved the skin and appendages, and 64 out of these reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs which most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the background of experimental data and the prescription rates of these substances.

Preliminary clinical data on a new photodynamic therapy photosensitizer: 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) for treatment of obstructive esophageal cancer

NASA Astrophysics Data System (ADS)

Dougherty, Thomas J.; Pandey, R. K.; Nava, Hector R.; Smith, Judy L.; Douglass, Harold O.; Edge, Stephen B.; Bellnier, David A.; O'Malley, Linda; Cooper, Michele

2000-03-01

The hexyl ether derivative or HPPH, has been identified as an optimal active in vivo photosensitizer in pre-clinical studies and has been evaluated clinically in obstructive esophageal cancer in five patients to date. The photosensitizer appears to have no systemic toxicity and be effective at low drug and light doses. Further, cutaneous photosensitivity appears to persist only 5-7 days.

Human photosensitivity: from pathophysiology to treatment.

PubMed

Verrotti, A; Tocco, A M; Salladini, C; Latini, G; Chiarelli, F

2005-11-01

Photosensitivity is a condition detected on the electroencephalography (EEG) as a paroxysmal reaction to Intermittent Photic Stimulation (IPS). This EEG response, elicited by IPS or by other visual stimuli of daily life, is called Photo Paroxysmal Response (PPR). PPRs are well documented in epileptic and non-epileptic subjects. Photosensitivity rarely in normal individuals evolves into epilepsy. Photosensitive epilepsy is a rare refex epilepsy characterized by seizures in photosensitive individuals. The development of modern technology has increased the exposition to potential seizure precipitants in people of all ages, but especially in children and adolescents. Actually, videogames, computers and televisions are the most common triggers in daily life of susceptible persons. The mechanisms of generation of PPR are poorly understood, but genetic factors play an important rule. The control of visually induced seizures has, generally a good prognosis. In patients known to be visually sensitive, avoidance of obvious source and stimulus modifications are very important and useful to seizure prevention, but in the large majority of patients with epilepsy and photosensitivity antiepileptic drugs are needed.

The photokilling of bladder carcinoma cells in vitro by phenothiazine dyes.

PubMed

Fowler, G J; Rees, R C; Devonshire, R

1990-09-01

The potential photodynamic therapy photosensitizers Methylene Blue, Azure C, Methylene Violet, Thionine, Methylene Green, Haematoporphyrin, Nile Blue A, chloroaluminium phthalocyanine and bis-aluminium phthalocyanine were examined for their photoeffects and dark toxicity against a human superficial bladder carcinoma cell-line. By examination of [3H]thymidine uptake into dye-treated cells after irradiation with a copper-vapour pumped dye laser, it was found that Methylene Blue was the most phototoxic and dark toxic of all the dyes tested, suggesting that the dye might be of some use as a topically applied photodrug for use in photodynamic therapy of superficial or early-recurring carcinomas.

Probing Photosensitization by Functionalized Carbon Nanotubes

EPA Science Inventory

Carbon nanotubes (CNTs) photosensitize the production of reactive oxygen species that can damage organisms by biomembrane oxidation or mediate CNTs' environmental transformations. The photosensitized nature of derivatized carbon nanotubes from various synthetic methods, and thus ...

Temperature Sensitive Singlet Oxygen Photosensitization by LOV-Derived Fluorescent Flavoproteins.

PubMed

Westberg, Michael; Bregnhøj, Mikkel; Etzerodt, Michael; Ogilby, Peter R

2017-03-30

Optogenetic sensitizers that selectively produce a given reactive oxygen species (ROS) constitute a promising tool for studying cell signaling processes with high levels of spatiotemporal control. However, to harness the full potential of this tool for live cell studies, the photophysics of currently available systems need to be explored further and optimized. Of particular interest in this regard, are the flavoproteins miniSOG and SOPP, both of which (1) contain the chromophore flavin mononucleotide, FMN, in a LOV-derived protein enclosure, and (2) photosensitize the production of singlet oxygen, O 2 (a 1 Δ g ). Here we present an extensive experimental study of the singlet and triplet state photophysics of FMN in SOPP and miniSOG over a physiologically relevant temperature range. Although changes in temperature only affect the singlet excited state photophysics slightly, the processes that influence the deactivation of the triplet excited state are more sensitive to temperature. Most notably, for both proteins, the rate constant for quenching of 3 FMN by ground state oxygen, O 2 (X 3 Σ g - ), increases ∼10-fold upon increasing the temperature from 10 to 43 °C, while the oxygen-independent channels of triplet state deactivation are less affected. As a consequence, this increase in temperature results in higher yields of O 2 (a 1 Δ g ) formation for both SOPP and miniSOG. We also show that the quantum yields of O 2 (a 1 Δ g ) production by both miniSOG and SOPP are mainly limited by the fraction of FMN triplet states quenched by O 2 (X 3 Σ g - ). The results presented herein provide a much-needed quantitative framework that will facilitate the future development of optogenetic ROS sensitizers.

No Photon Wasted: An Efficient and Selective Singlet Oxygen Photosensitizing Protein.

PubMed

Westberg, Michael; Bregnhøj, Mikkel; Etzerodt, Michael; Ogilby, Peter R

2017-10-12

Optogenetics has been, and will continue to be, a boon to mechanistic studies of cellular processes. Genetically encodable proteins that sensitize the production of reactive oxygen species (ROS) are expected to play an increasingly important role, particularly in elucidating mechanisms of temporally and spatially dependent cell signaling. However, a substantial challenge in developing such photosensitizing proteins has been to funnel the optical excitation energy into the initial selective production of only one ROS. Singlet molecular oxygen, O 2 (a 1 Δ g ), is a ROS known to have a wide range of effects on cell function. Nevertheless, mechanistic details of singlet oxygen's behavior in a cell are lacking. On the basis of the rational optimization of a LOV-derived flavoprotein, we now report the development and photophysical characterization of a protein-encased photosensitizer that efficiently and selectively produces singlet oxygen at the expense of other ROS, especially ROS that derive from photoinduced electron transfer reactions. These results set the stage for a plethora of new experiments to elucidate ROS-mediated events in cells.

Selenorhodamine Photosensitizers for Photodynamic Therapy of P-Glycoprotein-Expressing Cancer Cells

PubMed Central

2015-01-01

We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin. PMID:25250825

Eradication of bacterial species via photosensitization

NASA Astrophysics Data System (ADS)

Golding, Paul S.; Maddocks, L.; King, Terence A.; Drucker, D. B.

1999-02-01

Photosensitization and inactivation efficacy of three bacterial species: Prevotella nigrescens, Staphylococcus aureus and Escherichia coli have been investigated. Samples of Staphylococcus aureus and Escherichia coli were treated with the triphenylmethane dye malachite green isothiocyanate and exposed to light from a variety of continuous and pulsed light sauces at a wavelength of approximately 630 nm. Inactivation of the Gram-positive species Staphylococcus aureus was found to increase with radiation dose, whilst Gram-negative Escherichia coli was resistant to such treatment. Samples of the pigmented species Prevotella nigrescens were found to be inactivated by exposure to light alone. The mechanism of photosensitization and inactivation of Staphylococcus aureus with malachite green isothiocyanate is addressed. The possible roles of the excited triplet state of the photosensitizer, the involvement of molecular oxygen, and the bacterial cell wall are discussed. Photosensitization may provide a way of eliminating naturally pigmented species responsible for a variety of infections, including oral diseases such as gingivitis and periodontitis.

Phthalocyanines as photosensitizing agents for tumors--mechanism of action

NASA Astrophysics Data System (ADS)

Ben-Hur, Ehud

1994-03-01

Aluminum phthalocyanine (AlPc) is a second-generation photosensitizer under study for photodynamic therapy (PDT) of cancer. Its mechanism of action is not known. Fluoride appears to be a powerful probe for the mechanistic study of AlPc derivatives. F- forms a complex with the Al ligand, resulting in drastically reduced AlPc-induced phototoxicity. This is due to a modified binding of AlPc with certain target proteins, resulting in inhibition of electron transfer reactions (type I) but not singlet oxygen reactions (type II). In Chinese hamster ovary (CHO) cell membranes, Na+/K+-ATPase activity is selectively protected by F- from photosensitized inhibition by AlPc, suggesting that this enzyme may be a critical target for AlPc-PDT. Another cellular response, not interfered with by F-, is a transient increase of cytoplasmic free Ca2+ after AlPc-PDT. This increase was shown to trigger the induction of a recovery process.

Lipid based nanocarriers system for topical delivery of photosensitizers.

PubMed

Md, Shadab; Haque, Shadabul; Madheswaran, Thiagarajan; Zeeshan, Farrukh; Meka, Venkata Srikanth; Radhakrishnan, Ammu K; Kesharwani, Prashant

2017-08-01

Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Photophysical and Photochemical Properties of 3-methylpterin as a New and More Stable Pterin-type Photosensitizer.

PubMed

Estébanez, Sandra; Lorente, Carolina; Kaufman, Teodoro S; Larghi, Enrique L; Thomas, Andrés H; Serrano, Mariana P

2018-05-04

Pterin derivatives are heterocyclic compounds which are present in different biological systems. Neutral aqueous solutions of pterins presents acid-base and keto-enol equilibria. These compounds under UV-A radiation fluoresce, undergo photooxidation, generate reactive oxygen species, and photoinduce the oxidation of biological substrates. As photosensitizers, they may act through different mechanisms; mainly through an electron-transfer initiated process (type I mechanism), but they also produce singlet molecular oxygen ( 1 O 2 ) upon irradiation (type II mechanism). In general, upon UV-A excitation two triplet states, corresponding to the lactim and lactam tautomers, are formed, but only the last one is the responsible for the photosensitized reactions of biomolecules. We present a study of the photochemical properties of 3-methylpterin (3-Mep) which, in contrast to most pterin derivatives, exists only in the lactam form. Also an improvement in the synthesis of 3-Mep is reported. The spectroscopic properties 3-Mep in aqueous solution were similar to those of the unsubstituted pterin derivative (Ptr) in its acid form, such as absorption, fluorescent and phosphorescent emission spectra. Experiments using 2'-deoxyguanosine 5'-monophosphate (dGMP) as oxidizable target, demonstrated that methylation at C-3 position of the pterin moiety does not affect significantly the efficiency of photosensitization, but results in a more photostable sensitizer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Mechanism to preserve phrenic nerve function during photosensitization reaction: drug uptake and photosensitization reaction effect on electric propagation

NASA Astrophysics Data System (ADS)

Takahashi, Haruka; Hamada, Risa; Ogawa, Emiyu; Arai, Tsunenori

2018-02-01

To study a mechanism of phrenic nerve preservation phenomena during a photosensitization reaction, we investigated an uptake of talaporfin sodium and photosensitization reaction effect on an electric propagation. Right phrenic nerve was completely preserved after superior vena cava isolations using the photosensitization reaction in canine animal experiments, in spite of adjacent myocardium was electrically blocked. We predicted that low drug uptake and/or low photosensitization reaction effect on the nerve might be a mechanism of that phenomena. To investigate uptake to various nerve tissue, a healthy extracted crayfish ventral nerve cord and an extracted porcine phrenic nerve were immersed in 20 μg/ml talaporfin sodium solution for 0-240 min. The mean talaporfin sodium fluorescence brightness increased depending on the immersion time. This brightness saturated around the immersion time of 120 min. We found that talaporfin sodium uptake inside the perineurium which directly related to the electric propagation function was lower than that of outside in the porcine phrenic nerve. To investigate photosensitization reaction effect on electric propagation, the crayfish nerve was immersed into the same solution for 15 min and irradiated by a 663 nm laser light with 120 mW/cm2. Since we found the action potential disappeared when the irradiation time was 25-65 s, we consider that the crayfish nerve does not tolerant to the photosensitization reaction on electric propagation function at atmospheric pressure. From these results, we think that the low uptake of talaporfin sodium inside the perineurium and low oxygen partial pressure of nerve might be the possible mechanism to preserve phrenic nerve in vivo.

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

PubMed Central

Wu, Hao; Zeng, Fang; Zhang, Hang; Xu, Jiangsheng

2015-01-01

The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half‐life. Herein, a mitochondria‐targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio‐precursor of photosensitizer under two‐photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5‐aminolevulinic acid (5‐ALA, the bio‐precursor) to coumarin; and the nanosystem (CD‐ALA‐TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria‐targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs). Upon cellular internalization, the nanosystem preferentially accumulates in mitochondria; and under one‐ or two‐photon irradiation, it releases 5‐ALA molecules that are then metabolized into protoporphyrin IX in mitochondria through a series of biosynthesis processes. The subsequent red light irradiation induces this endogenously synthesized photosensitizer to generate singlet oxygen, thereby causing oxidant damage to mitochondria and then the apoptosis of the cells. Analysis via 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicate that the novel PDT system exhibits enhanced cytotoxicity toward cancer cells. This study may offer a new strategy for designing PDT systems with high efficacy and low side effects. PMID:27774388

CHD2 variants are a risk factor for photosensitivity in epilepsy

PubMed Central

Myers, Candace T.; Leu, Costin; de Kovel, Carolien G. F.; Afrikanova, Tatiana; Cordero-Maldonado, Maria Lorena; Martins, Teresa G.; Jacmin, Maxime; Drury, Suzanne; Krishna Chinthapalli, V.; Muhle, Hiltrud; Pendziwiat, Manuela; Sander, Thomas; Ruppert, Ann-Kathrin; Møller, Rikke S.; Thiele, Holger; Krause, Roland; Schubert, Julian; Lehesjoki, Anna-Elina; Nürnberg, Peter; Lerche, Holger; Palotie, Aarno; Coppola, Antonietta; Striano, Salvatore; Gaudio, Luigi Del; Boustred, Christopher; Schneider, Amy L.; Lench, Nicholas; Jocic-Jakubi, Bosanka; Covanis, Athanasios; Capovilla, Giuseppe; Veggiotti, Pierangelo; Piccioli, Marta; Parisi, Pasquale; Cantonetti, Laura; Sadleir, Lynette G.; Mullen, Saul A.; Berkovic, Samuel F.; Stephani, Ulrich; Helbig, Ingo; Crawford, Alexander D.; Esguerra, Camila V.; Kasteleijn-Nolst Trenité, Dorothee G. A.

2015-01-01

Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2·17 × 10−5). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3·50 × 10−4). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research

Internalization of aggregated photosensitizers by tumor cells: subcellular time-resolved fluorescence spectroscopy on derivatives of pyropheophorbide-a ethers and chlorin e6 under femtosecond one- and two-photon excitations.

PubMed

Kelbauskas, L; Dietel, W

2002-12-01

Amphiphilic sensitizers self-associate in aqueous environments and form aggregated species that exhibit no or only negligible photodynamic activity. However, amphiphilic photosensitizers number among the most potent agents of photodynamic therapy. The processes by which these sensitizers are internalized into tumor cells have yet to be fully elucidated and thus remain the subject of debate. In this study the uptake of photosensitizer aggregates into tumor cells was examined directly using subcellular time-resolved fluorescence spectroscopy with a high temporal resolution (20-30 ps) and high sensitivity (time-correlated single-photon counting). The investigations were performed on selected sensitizers that exhibit short fluorescence decay times (< 50 ps) in aggregated form. Derivatives of pyropheophorbide-a ether and chlorin e6 with varying lipophilicity were used for the study. The characteristic fluorescence decay times and spectroscopic features of the sensitizer aggregates measured in aqueous solution also could be observed in A431 human endothelial carcinoma cells administered with these photosensitizers. This shows that tumor cells can internalize sensitizers in aggregated form. Uptake of aggregates and their monomerization inside cells were demonstrated directly for the first time by means of fluorescence lifetime imaging with a high temporal resolution. Internalization of the aggregates seems to be endocytosis mediated. The degree of their monomerization in tumor cells is strongly influenced by the lipophilicity of the compounds.

Photosensitivity of layered semiconductor propolis heterocontact

NASA Astrophysics Data System (ADS)

Drapak, Stepan I.; Orletskii, Volodymyr B.; Bahtinov, Anatolii P.; Kovalyuk, Zakhar D.; Fotiy, Vasyl D.

2003-03-01

Room temperature photosensitivity and its spectral distribution are investigated for a hetercontact between a layered semiconductor (p-InSe) and a biological entity (propolis). The obtained heterocontacts has a maximum photosensitivity >= 10^4 V/W. It is shown that the form of spectral sensitivity curve depends on the way of the heterocontact preparation. The long-wave edge of relative quantum efficiency varies from hν =1.2 eV (the energy gap for InSe at T=300 K) to 1.6 eV depending on a state of aggregation of propolis. The maximum photosensitivity in the long-wave spectral range takes place when the propolis layer is under illumination. The obtained peculiarities of the photoelectrical properties cannot be explained in the framework of the classical description of photosensitivity spectral description (the window effect) what follows from the optical absorption measurements for InSe and propolis in the range hν <= 1.2 eV. Impurity states in the energy gap of InSe and states at the heterocontact interface (a classical case of isotype p-p heterojunction) also do not give an appropriate explanation. To interpret the obtained results the complexity of the chemical composition of propolis, a product from honey bee, must be taken into account.

Magnetic resonance spectroscopy findings in photosensitive idiopathic generalized epilepsy.

PubMed

Aydin-Ozemir, Zeynep; Terzibasioglu, Ege; Altindag, Ebru; Sencer, Serra; Baykan, Betul

2010-01-01

Studies investigating the pathophysiology of epileptic photosensitivity indicate variable involvement of particular brain regions. Our aim was to identify metabolic differences between photosensitive idiopathic generalized epilepsy (IGE) patients and nonphotosensitive IGE patients and normal healthy subjects by using Magnetic Resonance Spectroscopy (MRS). Fourteen patients diagnosed with photosensitive IGE were investigated. The control groups consisted of 14 age- and sex-matched healthy volunteers and 14 IGE patients without photosensitivity. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr) were performed in the frontal and occipital cortex and the thalamus bilaterally using a stimulated echo acquisition mode (STEAM) technique with a voxel size of 20 x 20 x 20 mm. The values of the patients with IGE were compared with those of the normal controls and within subgroups according to the clinical variables by appropriate statistical tests. Photosensitive IGE patients showed significantly decreased concentrations of NAA in the right frontal lobe and left thalamus, decreased NAA/Cr ratio in left thalamus and significantly increased concentrations of Cho/Cr ratio in the right frontal lobe and NAA/Cr in the left occipital lobe when compared to normal controls. Furthermore, left occipital NAA concentration increased and left thalamus NAA/Cr ratios were decreased from the IGE patients without photosensitivity but without reaching statistical significance. Our results support previous MR studies suggesting an asymmetrical neuronal dysfunction in favor of the dominant occipital cortex and thalamus in photosensitive IGE patients.

Novel visible light activated type 1 photosensitizers

NASA Astrophysics Data System (ADS)

Rajagopalan, Raghavan; Karwa, Amolkumar; Poreddy, Amruta R.; Lusiak, Przemyslaw M.; Pandurangi, Raghoottama S.; Cantrell, Gary L.; Dorshow, Richard B.

2010-02-01

Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation with visible light were prepared and tested for cell viability using U397 leukemia cell line. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light.

Effect of chirality on cellular uptake, imaging and photodynamic therapy of photosensitizers derived from chlorophyll-a.

PubMed

Srivatsan, Avinash; Pera, Paula; Joshi, Penny; Wang, Yanfang; Missert, Joseph R; Tracy, Erin C; Tabaczynski, Walter A; Yao, Rutao; Sajjad, Munawwar; Baumann, Heinz; Pandey, Ravindra K

2015-07-01

We have previously shown that the (124)I-analog of methyl 3-(1'-m-iodobenzyloxy) ethyl-3-devinyl-pyropheophorbide-a derived as racemic mixture from chlorophyll-a can be used for PET (positron emission tomography)-imaging in animal tumor models. On the other hand, as a non-radioactive analog, it showed excellent fluorescence and photodynamic therapy (PDT) efficacy. Thus, a single agent in a mixture of radioactive ((124)I-) and non-radioactive ((127)I) material can be used for both dual-imaging and PDT of cancer. Before advancing to Phase I human clinical trials, we evaluated the activity of the individual isomers as well as the impact of a chiral center at position-3(1) in directing in vitro/in vivo cellular uptake, intracellular localization, epithelial tumor cell-specific retention, fluorescence/PET imaging, and photosensitizing ability. The results indicate that both isomers (racemates), either as methyl ester or carboxylic acid, were equally effective. However, the methyl ester analogs, due to subcellular deposition into vesicular structures, were preferentially retained. All derivatives containing carboxylic acid at the position-17(2) were noted to be substrate for the ABCG2 (a member of the ATP binding cassette transporters) protein explaining their low retention in lung tumor cells expressing this transporter. The compounds in which the chirality at position-3 has been substituted by a non-chiral functionality showed reduced cellular uptake, retention and lower PDT efficacy in mice bearing murine Colon26 tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Photosensitizer fluorescence emission during photodynamic therapy applied to dermatological diseases

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

2011-09-01

Photodynamic Therapy (PDT) is an optical treatment modality that allows malignant tissue destruction. It is based on the administration of a photosensitizer and the posterior irradiation by an optical source. Photosensitizer molecules absorb the excitation light photons triggering a series of photochemical reactions in the presence of oxygen in the target tissue. During such interactions it is produced the de-excitation of the photosensitizer molecules in the singlet excited state which return to their minimum energy state by emitting fluorescence photons. These days, there are fixed clinical PDT protocols that make use of a particular optical dose and photosensitizer amount. However treatment response varies among patients and the type of pathology. In order to adjust an optimal dosimetry, the development of accurate predictive models plays an important role. The photosensitizer fluorescence can be used to estimate the degradation of the photoactive agent and as an implicit dosimetric measurement during treatment. However it is complex to know the fluorescence dependence with the depth in the tumor from observed fluorescence in the pathology surface. We present a first approach to predict the photosensitizer fluorescence dependence with depth during the PDT treatment applied to a skin disease commonly treated in the dermatological clinical practice. The obtained results permit us to know the photosensitizer temporal fluorescence evolution in different points of the tumor sample during the photochemical reactions involved in PDT with a predictive purpose related to the treatment evolution. The model presented also takes into account the distribution of a topical photosensitizer, the propagation of light in a biological media and the subsequent photochemical interactions between light and tissue. This implies that different parameters related with the photosensitizer distribution or the optical source characteristics could be adjusted to provide a specific treatment

Photosensitizer nanocarriers modeling for photodynamic therapy applied to dermatological diseases

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.

2011-02-01

Photodynamic Therapy involves the therapeutic use of photosensitizers in combination with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell death. This technique has become widely used in medicine to treat tumors and other nonmalignant diseases. However, there are several factors related to illumination or the photosensitizer that limit an optimal treatment outcome. The use of nanoparticles (NP) for PDT has been proposed as a solution to current shortcomings. In this way, there are NPs that act as carriers for photosensitizers, NPs that absorb the light and transfer the energy to the photosensitizer and NPs that are themselves photodynamically active. In dermatology, the use of topical photosensitizers produces a time dependent inhomogeneous distribution within the tumor, where the stratum corneum is the main barrier to the diffusion of the photosensitizer to the deeper layers of skin. This produces an insufficient photosensitizer accumulation in tumor tissues and therefore, a low therapeutic efficiency in the case of deep lesions. This work focuses in the use of NPs as photosensitizer carriers to improve the actual topical drug distribution in malignant skin tissues. We present a mathematical model of PS distribution in tumor tissue using NPs that takes into account parameters related to nanoparticles binding. Once the concentration profile of NPs into tissue is obtained, we use a photochemical model which allows us to calculate the temporal evolution of reactive oxygen species according to PS distribution calculated previously from NPs profile.

Investigation of human serum albumin (HSA) binding specificity of certain photosensitizers related to pyropheophorbide-a and bacteriopurpurinimide by circular dichroism spectroscopy and its correlation with in vivo photosensitizing efficacy.

PubMed

Chen, Yihui; Miclea, Razvan; Srikrishnan, Thamarapu; Balasubramanian, Sathyamangalam; Dougherty, Thomas J; Pandey, Ravindra K

2005-07-01

A series of pyropheophorbide-a and bacteriopurpurinimides were investigated to understand the correlation between HSA (site II) binding affinity and in vivo photosensitizing activity. In our study, photosensitizers that bound to site II of HSA produced a significant difference in the circular dichroism spectra of the corresponding complexes, especially at Soret band region of the photosensitizers. Our results suggest that CD spectroscopy of the photosensitizer-HSA complexes could be a valuable tool in screening new photosensitizers before evaluating them for in vivo efficacy.

Photosensitivity: a current biological overview.

PubMed

Elkeeb, Dena; Elkeeb, Laila; Maibach, Howard

2012-12-01

The level of interest in photoirritation (phototoxicity) has increased because of the awareness among the scientific community of the increase in the UV portion of the solar spectrum reaching the earth. The need of new chemicals and drugs puts pressure on pre-test methods for side effects, especially interactive adverse effects with UV light. So pre-marketing clinical trials conducted before a new drug is licensed are essential, as such, at the early phases of the discovery process of the drug/chemical, developing an efficacious photosensitivity testing system is prudent to avoid such potential side effects. To review published literature and provide an overview on exogenous photosensitivity and assays used to evaluate the photosensitivity potential of drugs/chemicals. As well as testing considerations by the Regulatory bodies (namely, the Organization for Economic Cooperation and Development, the U.S Food and Drug Administration and the European Union regulatory agencies). We searched medical and scientific search engines as well as websites of the EU and US Regulatory agencies and used keywords such as cutaneous phototoxicity, phototoxicity in vitro assays, phototoxicity in vivo assays and other related terms.

Development of Smart Phthalocyanine-based Photosensitizers for Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Chow, Yun Sang

Phthalocyanines are versatile functional dyes that have shown great potential in cancer theranostics, especially in photodynamic therapy (PDT). This research work aims to develop "smart" phthalocyanine-based photosensitizers for targeted PDT. This thesis describes the synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities of several series of carefully designed phthalocyanine-based photosensitizers. Chapter 1 presents an overview of PDT, including its historical development, photophysical mechanisms, and biological mechanisms. Various classes of photosensitizers are introduced with emphasis putting on phthalocyanines, which exhibit ideal characteristics of photosensitizers for PDT. In recent years, several approaches have been used to develop photosensitizers with higher tumor selectivity and minimal skin photosensitivity after PDT. Activatable photosensitizers can provide a "turn on" mechanism to offer an additional control of the specificity of treatment. Photosensitizers can also work cooperatively with the tumor-targeting groups or anticancer drugs so as to achieve targeted or dual therapy, which can enhance the efficacy of PDT. The novel approaches mentioned above have been widely used and combined to form multi-functional photosensitizing agents. These novel concepts and development of PDT are discussed and illustrated with relevant examples at the end of this chapter. To minimize the prolonged skin photosensitivity, photosensitizers that can only be activated by tumor-associated stimuli have been developed. Due to the abnormal metabolism in tumor tissues, their surface usually exhibits a lower pH compared to that of the normal tissues. Also, the pH difference between the intracellular and the physiological environment provides a pH-activation mechanism. Chapter 2 presents the synthesis and spectroscopic characterization of a pH-responsive zinc(II) phthalocyanine tetramer, in which the phthalocyanine units

A Photosensitizer-Loaded DNA Origami Nanosystem for Photodynamic Therapy.

PubMed

Zhuang, Xiaoxi; Ma, Xiaowei; Xue, Xiangdong; Jiang, Qiao; Song, Linlin; Dai, Luru; Zhang, Chunqiu; Jin, Shubin; Yang, Keni; Ding, Baoquan; Wang, Paul C; Liang, Xing-Jie

2016-03-22

Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.

Amphiphilic zinc phthalocyanine photosensitizers: synthesis, photophysicochemical properties and in vitro studies for photodynamic therapy.

PubMed

Çakır, Dilek; Göksel, Meltem; Çakır, Volkan; Durmuş, Mahmut; Biyiklioglu, Zekeriya; Kantekin, Halit

2015-05-28

Peripherally and non-peripherally tetra-substituted zinc(ii) phthalocyanines bearing 2-(2-{2-[3-(dimethylamino)phenoxy]ethoxy}ethoxy)ethoxy and 2-(2-{2-[3-(diethylamino)phenoxy]ethoxy}ethoxy)ethoxy groups (, , and ) were synthesized by cyclotetramerization of the corresponding phthalonitriles (, , and ). Their quaternized ionic derivatives (, , and ) were also synthesized by the reaction of them with methyl iodide. The novel compounds were characterized by using standard spectroscopic techniques such as FT-IR, (1)H NMR, (13)C NMR, UV-vis, mass and elemental analyses. The obtained quaternized phthalocyanines (, , and ) showed amphiphilic behaviour with excellent solubility in both organic and aqueous solutions, which makes them potential photosensitizers for use in photodynamic therapy (PDT) of cancer. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yields) properties of these novel phthalocyanines were studied in DMSO for both non-ionic and ionic quaternized derivatives. However, these properties were examined in both DMSO and phosphate buffer solution (PBS) for quaternized ionic phthalocyanines. The effects of the positions of substituents (peripheral or non-peripheral) and the quaternization of the nitrogen atoms on the substituents about their photophysical and photochemical properties were also compared in this study. The bovine serum albumin (BSA) binding behaviours of the studied quaternized ionic zinc(ii) phthalocyanines were also described in PBS solutions. The quaternized phthalocyanines (, , and ) successfully displayed light-dependent photodamage in HeLa and HuH-7 cancer cells in photodynamic therapy treatment. The photosensitivity and the intensity of damage were found directly related to the concentration of the photosensitizers.

Antimicrobial and anticancer photodynamic activity of a phthalocyanine photosensitizer with N-methyl morpholiniumethoxy substituents in non-peripheral positions.

PubMed

Dlugaszewska, Jolanta; Szczolko, Wojciech; Koczorowski, Tomasz; Skupin-Mrugalska, Paulina; Teubert, Anna; Konopka, Krystyna; Kucinska, Malgorzata; Murias, Marek; Düzgüneş, Nejat; Mielcarek, Jadwiga; Goslinski, Tomasz

2017-07-01

Photodynamic therapy involves the use of a photosensitizer that is irradiated with visible light in the presence of oxygen, resulting in the formation of reactive oxygen species. A novel phthalocyanine derivative, the quaternary iodide salt of magnesium(II) phthalocyanine with N-methyl morpholiniumethoxy substituents, was synthesized, and characterized. The techniques used included mass spectrometry (MALDI TOF), UV-vis, NMR spectroscopy, and photocytotoxicity against bacteria, fungi and cancer cells. The phthalocyanine derivative possessed typical characteristics of compounds of the phthalocyanine family but the effect of quaternization was observed on the optical properties, especially in terms of absorption efficiency. The results of the photodynamic antimicrobial effect study demonstrated that cationic phthalocyanine possesses excellent photodynamic activity against planktonic cells of both Gram-positive and Gram-negative bacteria. The bactericidal effect was dose-dependent and all bacterial strains tested were killed to a significant degree by irradiated phthalocyanine at a concentration of 1×10 -4 M. There were no significant differences in the susceptibility of Gram-positive and Gram-negative bacteria to the applied photosensitizer. The photosensitivity of bacteria in the biofilm was lower than that in planktonic form. No correlation was found between the degree of biofilm formation and susceptibility to antimicrobial photodynamic inactivation. The anticancer activity of the novel phthalocyanine derivative was tested using A549 adenocarcinomic alveolar basal epithelial cells and the human oral squamous cell carcinoma cells derived from tongue (HSC3) or buccal mucosa (H413). No significant decrease in cell viability was observed under different conditions or with different formulations of the compound. Copyright © 2017 Elsevier Inc. All rights reserved.

Pentalysine β-Carbonylphthalocyanine Zinc: An Effective Tumor-Targeting Photosensitizer for Photodynamic Therapy

PubMed Central

Chen, Zhuo; Zhou, Shanyong; Chen, Jincan; Deng, Yicai; Luo, Zhipu; Chen, Hongwei; Hamblin, Michael R.

2010-01-01

Unsymmetrical phthalocyanine derivatives have been widely studied as photosensitizers for photodynamic therapy (PDT), targeting various tumor types. However, the preparation of unsymmetrical phthalocyanines is always a challenge due to the presence of many possible structural isomers. Herein we report a new unsymmetrical zinc phthalocyanine, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5), that was prepared in large quantity and high purity. This is a water-soluble cationic photosensitizer and maintains a high quantum yield of singlet oxygen generation similar to that of unsubstituted zinc phthalocyanine (ZnPc). Compared with anionic ZnPc counterparts, ZnPc-(Lys)5 shows a higher level cellular uptake and 20-fold higher phototoxicity toward tumor cells. Pharmacokinetics and PDT studies of ZnPc-(Lys)5 in S180 tumor-bearing mice showed a high ratio of tumor versus skin retention and significant tumor inhibition. This new molecular framework will allow synthetic diversity in the number of lysine residues incorporated and will facilitate future QSAR studies. PMID:20458713

In-vivo NMR studies of deuterium-labeled photosensitizers in mice tumor model

NASA Astrophysics Data System (ADS)

Ramaprasad, Subbaraya; Liu, Y. H.; Pandey, R. K.; Shiau, Fuu-Yau; Smith, Kevin M.

1993-06-01

Photodynamic therapy (PDT) has emerged as a promising modality for the treatment of cancer. We are using newly synthesized and chemically defined and characterized porphyrin photosensitizers that are specifically labeled with deuterium to perform in vivo NMR studies in a murine tumor model. In vivo magnetic resonance offers the potential for repetitive, safe, noninvasive evaluation of photosensitizers, tumor metabolism, and the effect of PDT on the tumor metabolism. In an effort to monitor noninvasively the photosensitizers in an in vivo tumor model, we are synthesizing several deuterium labeled photosensitizers which absorb red light at or above 630 nm. Development of methods to test these photosensitizers directly in humans is not feasible at this time, since these photosensitizers are new and we do not yet understand the side effects. In addition, we do not understand the potential benefits compared with Photofrin II, the widely used photosensitizer. To perform our in vivo deuterium NMR studies on mouse foot tumors, we have constructed a solenoid coil which operates at 30.7 MHz for the deuterium nucleus. We have been able to detect the deuterium labeled photosensitizer in the tumor after a direct intra-tumor injection. The use of 31P NMR to predict the possible outcome of PDT in these tumors is also discussed.

[Photosensitization and photoprotection by some drugs, metabolites and other compounds].

PubMed

Lozovskaia, E L; Makareeva, E N; Makedonov, I U

1997-01-01

Photosensitizing and photoprotecting efficiency of about a hundred of compounds, mainly drugs, was studied. The method based on chemiluminescence occurred along with photooxidation of glycyltryptophan under irradiation in UVB range in solution was used for testing. As a measure of photosensitizing efficiency the concentration of photosensitizer which induced two-fold increase of chemiluminescence intensity was chosen. The most effective photosensitizers are riboflavin, FAD, furagin, psoralene, vicasol, benzobarbital, mydocalm, angelicyn, furadonin, ethacridin, diazolin, folic acid. With regard to pharmacological doses of drugs in organism more dangerous sensitizers (in descending order) are p-aminosalicylic acid, furagin, riboflavin, benzobarbital, thiopental, chloramphenicol, nicodin, mydocalm, furadonin, oxolonic acid, furazolidone, psoralene, nicotinamide and diazolin. Photoprotecting effect was described by the concentration at which chemiluminescence intensity decreased twice. The most effective photoprotectors are etamsilat, quercetin, ftivazid, chlorpromazine, diprazine, thioridazine, aminophenazone, oxaphenamide. Concentration dependence for some of these drugs (etamsilat, chlorpromazine, diprazine, thioridazine) is non-monotonous: they inhibit photooxidation in low concentration (about 10(-7)-10(-6) M), but at higher concentrations (10(-5)-10(-4) M) photosensitization dominates over photoprotection.

Photosensitized oxidation of unsaturated polymers

NASA Technical Reports Server (NTRS)

Golub, M. A.

1979-01-01

The photosensitized oxidation or singlet oxygenation of unsaturated hydrocarbon polymers and of their model compounds was reviewed. Emphasis was on cis and trans forms of 1,4-polyisoprene, 1,4-polybutadiene and 1,2-poly(1,4-hexadiene), and on 1,4-poly(2,3-dimethyl-1,3-butadiene). The microstructural changes which occur in these polymers on reaction with O2-1 in solution were investigated by infrared H-1 and C-13 NMR spectroscopy. The polymers were shown to yield allylic hydroperoxides with shifted double bonds according to the ene mechanism established for simple olefins. The photosensitized oxidation of the above unsaturated polymer exhibited zero order kinetics, the relative rates paralleling the reactivities of the corresponding simple olefins towards O2-1.

The phototoxicity of phenothiazinium-based photosensitizers to bacterial membranes.

PubMed

Hussain, Saimah; Harris, Frederick; Phoenix, David A

2006-02-01

The ability of phenothiazinium-based photosensitizers to induce photodamage to Escherichia coli membranes is investigated. Phenothiazinium-based photosensitizers were found to be somewhat lipophilic (log P>0.7) and to induce surface-pressure changes (3-12 mN m(-1)) in lipid monolayers mimetic of bacterial membranes, implying that these molecules are able to penetrate biological membranes. Under dark and light conditions (3.15 J cm(-1) for 30 min), phenothiazinium-based photosensitizers were incubated with E. coli cells. These cells showed levels of dark bacteriolysis that ranged between 6% and 13%, with light conditions leading to no significant increase in these levels. Gas chromatography-based analyses showed such incubations to produce no significant changes in the levels of C(16) and C(18) fatty acid chain saturation found in E. coli whole lipid-extracts. It is concluded that the phenothiazinium-based photosensitizers studied may not use E. coli membranes as their primary photodynamic target, but may inflict photodamage on cytoplasmic targets, possibly DNA.

Anticancer activity of the new photosensitizers: dose and cell type dependence

NASA Astrophysics Data System (ADS)

Gyulkhandanyan, Grigor V.; Ghambaryan, Sona S.; Amelyan, Gayane V.; Ghazaryan, Robert K.; Haroutiunian, Samvel G.; Gyulkhandanyan, Aram G.; Gasparyan, Gennadi H.

2005-04-01

The necessity of researches of antitumor efficiency of new photosensitizers (PS) is explained by the opportunity of their application in photodynamic therapy of tumors. PS, selectively accumulated in cancer cells and activated by the light, generate the active oxygen species that cause apoptosis. Earlier, it was shown that PS chlorin e6 (0.3-0.5 μg/ml) induces rat embryo fibroblast-like cell apoptosis. In present work antitumor activity of the new photosensitizers, water-soluble cationic porphyrins and their metal complexes, is investigated. The dose-dependent destruction of cancer cells was shown on PC-12 (pheochromocytoma, rat adrenal gland) and Jurkat (human lymphoma) cell lines. Meso-tetra-[4-N-(2 `- oxyethyl) pyridyl] porphyrin (TOEPyP) and chlorin e6 possessed the same toxicity at LD50 dose on PC-12 cell line, whereas phototoxicity of TOEPyP was 3 times less compared to chlorin e6(LD50=0.2 and 0.075 μg/ml accordingly). The results have shown weak photosensitizing effect of Zn-and Ag-derivatives of TOEPyP on PC-12 cell line. TOEPyP and Zn-TOEPyP (0.1 - 50 μg/ml) were non-toxic for Jurkat cell line, whereas Ag-TOEPyP was toxic at 10 μg/ml (LD90). TOEPyP and chlorin e6 have shown phototoxic effect in the same dose range (LD50=0.5 and 0.3 μg/ml accordingly). The investigation of toxic and phototoxic effects of the new porphyrins revealed significantly different sensitivity of various cell lines to PSs.

Photosensitizer-Embedded Polyacrylonitrile Nanofibers as Antimicrobial Non-Woven Textile

PubMed Central

Stanley, Sarah L.; Scholle, Frank; Zhu, Jiadeng; Lu, Yao; Zhang, Xiangwu; Situ, Xingci; Ghiladi, Reza A.

2016-01-01

Toward the objective of developing platform technologies for anti-infective materials based upon photodynamic inactivation, we employed electrospinning to prepare a non-woven textile comprised of polyacrylonitrile nanofibers embedded with a porphyrin-based cationic photosensitizer; termed PAN-Por(+). Photosensitizer loading was determined to be 34.8 nmol/mg material; with thermostability to 300 °C. Antibacterial efficacy was evaluated against four bacteria belonging to the ESKAPE family of pathogens (Staphylococcus aureus; vancomycin-resistant Enterococcus faecium; Acinetobacter baumannii; and Klebsiella pneumonia), as well as Escherichia coli. Our results demonstrated broad photodynamic inactivation of all bacterial strains studied upon illumination (30 min; 65 ± 5 mW/cm2; 400–700 nm) by a minimum of 99.9996+% (5.8 log units) regardless of taxonomic classification. PAN-Por(+) also inactivated human adenovirus-5 (~99.8% reduction in PFU/mL) and vesicular stomatitis virus (>7 log units reduction in PFU/mL). When compared to cellulose-based materials employing this same photosensitizer; the higher levels of photodynamic inactivation achieved here with PAN-Por(+) are likely due to the combined effects of higher photosensitizer loading and a greater surface area imparted by the use of nanofibers. These results demonstrate the potential of photosensitizer-embedded polyacrylonitrile nanofibers to serve as scalable scaffolds for anti-infective or self-sterilizing materials against both bacteria and viruses when employing a photodynamic inactivation mode of action. PMID:28335205

Evaluation of different photosensitizers for use in photochemical gene transfection.

PubMed

Prasmickaite, L; Høgset, A; Berg, K

2001-04-01

Many potentially therapeutic macromolecules, e.g. transgenes used in gene therapy, are taken into the cells by endocytosis, and have to be liberated from endocytic vesicles in order to express a therapeutic function. To achieve this we have developed a new technology, named photochemical internalization (PCI), based on photochemical reactions inducing rupture of endocytic vesicles. The aim of this study was to clarify which properties of photosensitizers are important for obtaining the PCI effect improving gene transfection. The photochemical effect on transfection of human melanoma THX cells has been studied employing photosensitizers with different physicochemical properties and using two gene delivery vectors: the cationic polypeptide polylysine and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Photochemical treatment by photosensitizers that do not localize in endocytic vesicles (tetra[3-hydroxyphenyl]porphyrin and 5-aminolevulinic acid-induced protoporphyrin IX) do not stimulate transfection, irrespective of the gene delivery vector. In contrast, photosensitizers localized in endocytic vesicles stimulate polylysine-mediated transfection, and amphiphilic photosensitizers (disulfonated aluminium phthalocyanine [AlPcS2a] and meso-tetraphenylporphynes) show the strongest positive effect, inducing approximately 10-fold increase in transfection efficiency. In contrast, DOTAP-mediated transfection is inhibited by all photochemical treatments irrespective of the photosensitizer used. Neither AlPcS2a nor Photofrin affects the uptake of the transfecting DNA over the plasma membrane, therefore photochemical permeabilization of endocytic vesicles seems to be the most likely mechanism responsible for the positive PCI effect on gene transfection.

In vitro lethal photosensitization of S. mutans using methylene blue and toluidine blue O as photosensitizers.

PubMed

Araújo, Patrícia V; Teixeira, Karina I R; Lanza, Lincoln D; Cortes, Maria E; Poletto, Luiz T A

2009-01-01

The purpose of this in vitro study was to evaluate the antimicrobial effect of photodynamic therapy on Streptococcus mutans (A TCC 25175) suspensions, using a red laser for one minute in combination with toluidine blue O (TBO) or methylene blue (MB). Both photosensitizers were used in three concentrations (25, 10 and 5 mg/L). The activity ofphotosensitizers and laser irradiation were tested separately on the bacteria, as well as the irradiation of this light source in the presence of the TBO or MB. These groups were compared to a control group, in which the microorganism did not receive any treatment. The activity of both TBO and MB or laser irradiation, alone, were not able to reduce the number of S. mutans. In the groups of lethal photosensitization, a bacterial reduction of 70% for TBO and 73% for MB was observed when these photosensitizers were used at 25 mg/L and a reduction of 48% was observed for MB at 5mg/L. In other concentrations there were no significant differences in comparison to the control group. Both the TBO and the MB at 25 mg/L associated with a red laser had an excellent potential for use in PDT in lethal sensitization of S. mutans.

A novel automated instrument designed to determine photosensitivity thresholds (Conference Presentation)

NASA Astrophysics Data System (ADS)

Aguilar, Mariela C.; Gonzalez, Alex; Rowaan, Cornelis; De Freitas, Carolina; Rosa, Potyra R.; Alawa, Karam; Lam, Byron L.; Parel, Jean-Marie A.

2016-03-01

As there is no clinically available instrument to systematically and reliably determine the photosensitivity thresholds of patients with dry eyes, blepharospasms, migraines, traumatic brain injuries, and genetic disorders such as Achromatopsia, retinitis pigmentosa and other retinal dysfunctions, a computer-controlled optoelectronics system was designed. The BPEI Photosensitivity System provides a light stimuli emitted from a bi-cupola concave, 210 white LED array with varying intensity ranging from 1 to 32,000 lux. The system can either utilize a normal or an enhanced testing mode for subjects with low light tolerance. The automated instrument adjusts the intensity of each light stimulus. The subject is instructed to indicate discomfort by pressing a hand-held button. Reliability of the responses is tracked during the test. The photosensitivity threshold is then calculated after 10 response reversals. In a preliminary study, we demonstrated that subjects suffering from Achromatopsia experienced lower photosensitivity thresholds than normal subjects. Hence, the system can safely and reliably determine the photosensitivity thresholds of healthy and light sensitive subjects by detecting and quantifying the individual differences. Future studies will be performed with this system to determine the photosensitivity threshold differences between normal subjects and subjects suffering from other conditions that affect light sensitivity.

Solid state photosensitive devices which employ isolated photosynthetic complexes

DOEpatents

Peumans, Peter; Forrest, Stephen R.

2009-09-22

Solid state photosensitive devices including photovoltaic devices are provided which comprise a first electrode and a second electrode in superposed relation; and at least one isolated Light Harvesting Complex (LHC) between the electrodes. Preferred photosensitive devices comprise an electron transport layer formed of a first photoconductive organic semiconductor material, adjacent to the LHC, disposed between the first electrode and the LHC; and a hole transport layer formed of a second photoconductive organic semiconductor material, adjacent to the LHC, disposed between the second electrode and the LHC. Solid state photosensitive devices of the present invention may comprise at least one additional layer of photoconductive organic semiconductor material disposed between the first electrode and the electron transport layer; and at least one additional layer of photoconductive organic semiconductor material, disposed between the second electrode and the hole transport layer. Methods of generating photocurrent are provided which comprise exposing a photovoltaic device of the present invention to light. Electronic devices are provided which comprise a solid state photosensitive device of the present invention.

Exploration of photosensitive polyimide as the modification layer in thin film microcircuit

NASA Astrophysics Data System (ADS)

Liu, Lily; Song, Changbin; Xue, Bin; Li, Jing; Wang, Junxi; Li, Jinmin

2018-02-01

Positive type photosensitive polyimide is used as the modification layer in the thin film transistors production process. The photosensitive polyimide is not only used as the second insulating layer, it can also be used instead of a mask because of the photosensitivity. A suitable curing condition can help photosensitive polyimide form the high performance polyimide with orderly texture inside, and the performance of imidization depends on the precise control of temperature, time, and heat control during the curing process. Therefore, experiments of different stepped up heating tests are made, and the ability of protecting silicon dioxide is analyzed.

Separation of porphyrin-based photosensitizer isomers by laser-induced fluorescence capillary electrophoresis.

PubMed

Peng, Xuejun; Sternberg, Ethan; Dolphin, David

2005-10-01

Methods for the separation of photosensitizer isomers, such as benzoporphyrin derivative monoacid, benzoporphyrin ethyl monoacid, 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a, diethyleneglycol diester benzoporphyrin derivative, tin ethyl etiopurpurin, and phthalocyanine tetrasulfonate, have been systematically developed by CE. Detection was accomplished by UV absorption at 214 nm or by LIF with excitation at 442/488 nm and emission at 690 nm. The effects of three major experimental parameters of buffer types, organic solvents, and surfactant additives are described. The optimized separation conditions were determined so as to provide satisfactory separation efficiency and analysis time. The methods are shown to be suitable for the separation and determination of porphyrin and phthalocyanines regioisomers, diastereoisomers, and enantiomers.

Singlet oxygen-sensitized delayed fluorescence of common water-soluble photosensitizers.

PubMed

Scholz, Marek; Dědic, Roman; Breitenbach, Thomas; Hála, Jan

2013-10-01

Six common water-soluble singlet oxygen ((1)O2) photosensitizers - 5,10,15,20-tetrakis(1-methyl-4-pyridinio) porphine (TMPyP), meso-tetrakis(4-sulfonathophenyl)porphine (TPPS4), Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4), eosin Y, rose bengal, and methylene blue - were investigated in terms of their ability to produce delayed fluorescence (DF) in solutions at room temperature. All the photosensitizers dissolved in air-saturated phosphate buffered saline (PBS, pH 7.4) exhibit easily detectable DF, which can be nearly completely quenched by 10 mM NaN3, a specific (1)O2 quencher. The DF kinetics has a biexponential rise-decay character in a microsecond time domain. Therefore, we propose that singlet oxygen-sensitized delayed fluorescence (SOSDF), where the triplet state of a photosensitizer reacts with (1)O2 giving rise to an excited singlet state of the photosensitizer, is the prevailing mechanism. It was confirmed by additional evidence, such as a monoexponential decay of triplet-triplet transient absorption kinetics, dependence of SOSDF kinetics on oxygen concentration, absence of SOSDF in a nitrogen-saturated sample, or the effect of isotopic exchange H2O-D2O. Eosin Y and AlPcS4 show the largest SOSDF quantum yield among the selected photosensitizers, whereas rose bengal possesses the highest ratio of SOSDF intensity to prompt fluorescence intensity. The rate constant for the reaction of triplet state with (1)O2 giving rise to the excited singlet state of photosensitizer was estimated to be ~/>1 × 10(9) M(-1) s(-1). SOSDF kinetics contains information about both triplet and (1)O2 lifetimes and concentrations, which makes it a very useful alternative tool for monitoring photosensitizing and (1)O2 quenching processes, allowing its detection in the visible spectral region, utilizing the photosensitizer itself as a (1)O2 probe. Under our experimental conditions, SOSDF was up to three orders of magnitude more intense than the infrared (1)O2

Fluorescent proteins as singlet oxygen photosensitizers: mechanistic studies in photodynamic inactivation of bacteria

NASA Astrophysics Data System (ADS)

Ruiz-González, Rubén.; White, John H.; Cortajarena, Aitziber L.; Agut, Montserrat; Nonell, Santi; Flors, Cristina

2013-02-01

Antimicrobial photodynamic therapy (aPDT) combines a photosensitizer, light and oxygen to produce reactive oxygen species (ROS), mainly singlet oxygen (1O2), to photo-oxidize important biomolecules and induce cell death. aPDT is a promising alternative to standard antimicrobial strategies, but its mechanisms of action are not well understood. One of the reasons for that is the lack of control of the photosensitizing drugs location. Here we report the use of geneticallyencoded fluorescent proteins that are also 1O2 photosensitizers to address the latter issue. First, we have chosen the red fluorescent protein TagRFP as a photosensitizer, which unlike other fluorescent proteins such as KillerRed, is able to produce 1O2 but not other ROS. TagRFP photosensitizes 1O2 with a small, but not negligible, quantum yield. In addition, we have used miniSOG, a more efficient 1O2 photosensitizing fluorescent flavoprotein that has been recently engineered from phototropin 2. We have genetically incorporated these two photosensitizers into the cytosol of E. coli and demonstrated that intracellular 1O2 is sufficient to kill bacteria. Additional assays have provided further insight into the mechanism of cell death. Photodamage seems to occur primarily in the inner membrane, and extends to the outer membrane if the photosensitizer's efficiency is high enough. These observations are markedly different to those reported for external photosensitizers, suggesting that the site where 1O2 is primarily generated proves crucial for inflicting different types of cell damage.

Photosensitized electron transport across lipid vesicle walls: quantum yield dependence on sensitizer concentration.

PubMed Central

Ford, W E; Otvos, J W; Calvin, M

1979-01-01

An amphiphilic tris(2,2'-bipyridine)ruthenium(2+) derivative that is incorporated into the walls of phosphatidylcholine vesicles photosensitizes the irreversible oxidation of ethylenediaminetetraacetate(3-) dissolved in the inner aqueous compartments of the vesicle suspension and the one-electron reduction of heptylviologen(2+) dissolved in the continuous aqueous phase. The quantum yield of viologen radical production depends on the phospholipid-to-ruthenium complex mole ratios. A kinetic model is used to derive an order-of-magnitude estimate for the rate constant of electron transport across the vesicle walls. The results are inconsistent with a diffusional mechanism for electron transport and are interpreted in terms of electron exchange. PMID:291027

Clinical status of benzoporphyrin derivative

NASA Astrophysics Data System (ADS)

Levy, Julia G.; Chan, Agnes H.; Strong, H. Andrew

1996-01-01

Benzoporphyrin derivative monoacid ring A (BPD) is currently in Phase II clinical trials for the treatment of cutaneous malignancies (basal cell carcinoma and cutaneous metastases) and psoriasis. Results to date suggest that this photosensitizer has potential in both of these areas. Recently, a clinical trial with BPD was initiated for the treatment of age related macular degeneration, a neovascular condition in the eye which leads to blindness. BPD is a lipophilic photosensitizer which is rapidly taken up by activated cells and the vascular endothelium of neovasculature. The PDT effects seen with BPD appear to be a combination of vascular occlusion and direct killing of target cells. Since many diseases involve either activated cells and/or neovasculature, PDT with photosensitizer with characteristics like those of BPD, has applications far wider than oncology. A new area of interest involving photosensitizers is that of immune modulation. A number of photosensitizers have been shown to effect immune modulation in animal models of immune dysfunction including autoimmunity (rheumatoid arthritis, lupus), cutaneous hypersensitivity and allografts. BPD and PHOTOFRINR have both been shown to be effective in ameliorating arthritic symptoms in a number of animal models. The mechanisms by which immune modulation is affected in these studies still remains to be resolved.

[Synthesis and properties of O- and S-glycosylated derivatives of pyropheophorbide a].

PubMed

Aksenova, A A; Sebiakin, Iu L; Mironov, A F

2001-01-01

New O- and S-glycosylated derivatives of pyropheophorbide a were synthesized in the context of the design of photosensitizers for photodynamic cancer therapy. The resulting amphiphilic conjugates were found to be sufficiently water-soluble and suitable for the study of the photosensitizer penetration and accumulation in tumors.

Photosensitized Chemically Amplified Resist (PSCAR) 2.0 for high-throughput and high-resolution EUV lithography: dual photosensitization of acid generation and quencher decomposition by flood exposure

NASA Astrophysics Data System (ADS)

Nagahara, Seiji; Carcasi, Michael; Shiraishi, Gosuke; Nakagawa, Hisashi; Dei, Satoshi; Shiozawa, Takahiro; Nafus, Kathleen; De Simone, Danilo; Vandenberghe, Geert; Stock, Hans-Jürgen; Küchler, Bernd; Hori, Masafumi; Naruoka, Takehiko; Nagai, Tomoki; Minekawa, Yukie; Iseki, Tomohiro; Kondo, Yoshihiro; Yoshihara, Kosuke; Kamei, Yuya; Tomono, Masaru; Shimada, Ryo; Biesemans, Serge; Nakashima, Hideo; Foubert, Philippe; Buitrago, Elizabeth; Vockenhuber, Michaela; Ekinci, Yasin; Oshima, Akihiro; Tagawa, Seiichi

2017-03-01

A new type of Photosensitized Chemically Amplified Resist (PSCAR) **: "PSCAR 2.0," is introduced in this paper. PSCAR 2.0 is composed of a protected polymer, a "photo acid generator which can be photosensitized" (PS-PAG), a "photo decomposable base (quencher) which can be photosensitized" (PS-PDB) and a photosensitizer precursor (PP). With this PSCAR 2.0, a photosensitizer (PS) is generated by an extreme ultra-violet (EUV) pattern exposure. Then, during a subsequent flood exposure, PS selectively photosensitizes the EUV exposed areas by the decomposition of a PS-PDB in addition to the decomposition of PS-PAG. As these pattern-exposed areas have the additional acid and reduced quencher concentration, the initial quencher loading in PSCAR 2.0 can be increased in order to get the same target critical dimensions (CD). The quencher loading is to be optimized simultaneously with a UV flood exposure dose to achieve the best lithographic performance and resolution. In this work, the PSCAR performance when different quenchers are used is examined by simulation and exposure experiments with the 16 nm half-pitch (HP) line/space (L/S, 1:1) patterns. According to our simulation results among resists with the different quencher types, the best performance was achieved by PSCAR 2.0 using PS-PDB with the highest possible chemical gradient resulting in the lowest line width roughness (LWR). PSCAR 2.0 performance has furthermore been confirmed on ASML's NXE:3300 with TEL's standalone pre-alpha flood exposure tool at imec. The initial PSCAR 2.0 patterning results on NXE:3300 showed the accelerated photosensitization performance with PS-PDB. From these results, we concluded that the dual sensitization of PS-PAG and PS-PDB in PSCAR 2.0 have a potential to realize a significantly improved resist performance in EUV lithography.

Endoplasmic Reticulum-Localized Two-Photon-Absorbing Boron Dipyrromethenes as Advanced Photosensitizers for Photodynamic Therapy.

PubMed

Zhou, Yimin; Cheung, Ying-Kit; Ma, Chao; Zhao, Shirui; Gao, Di; Lo, Pui-Chi; Fong, Wing-Ping; Wong, Kam Sing; Ng, Dennis K P

2018-05-10

Two advanced boron dipyrromethene (BODIPY) based photosensitizers have been synthesized and characterized. With a glibenclamide analogous moiety, these compounds can localize in the endoplasmic reticulum (ER) of HeLa human cervical carcinoma cells and HepG2 human hepatocarcinoma cells. The BODIPY π skeleton is conjugated with two styryl or carbazolylethenyl groups, which can substantially red-shift the Q-band absorption and fluorescence emission and impart two-photon absorption (TPA) property to the chromophores. The TPA cross section of the carbazole-containing analogue reaches a value of 453 GM at 1010 nm. These compounds also behave as singlet oxygen generators with high photostability. Upon irradiation at λ > 610 nm, these photosensitizers cause photocytotoxicity to these two cell lines with IC 50 values down to 0.09 μM, for which the cell death is triggered mainly by ER stress. The two-photon photodynamic activity of the distyryl derivative upon excitation at λ = 800 nm has also been demonstrated.

Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

PubMed Central

Yoon, Il; Li, Jia Zhu

2013-01-01

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo. PMID:23423543

Photosensitized oxidation of nicotinamide adenine dinucleotide by diethoxyphosphorus(V)tetraphenylporphyrin and its fluorinated derivative: Possibility of chain reaction

NASA Astrophysics Data System (ADS)

Hirakawa, Kazutaka; Murata, Atsushi

2018-01-01

Water-soluble porphyrins, diethoxyphosphorus(V)tetraphenylporphyrin (EtP(V)TPP) and its fluorinated analogue (FEtP(V)TPP), decreased the typical absorption around 340 nm of nicotinamide adenine dinucleotide (NADH) under visible light irradiation, indicating oxidative decomposition. A singlet oxygen quencher, sodium azide, and a triplet quencher, potassium iodide, slightly inhibited photosensitized NADH oxidation. However, these inhibitory effects were very small. Furthermore, the fluorescence lifetime of these P(V)porphyrins was decreased by NADH, suggesting the contribution of electron transfer to the singlet excited (S1) state of P(V)porphyrin. The redox potential measurement supports the electron transfer-mediated oxidation of NADH. The quantum yields of NADH photodecomposition by P(V)porphyrins could be estimated from the kinetic data and the effect of these quenchers on NADH oxidation. The obtained values suggest that the electron accepting by the S1 states of P(V)porphyrins triggers a chain reaction of NADH oxidation. This photosensitized reaction may play an important role in the photocytotoxicity of P(V)porphyrins. The axial ligand fluorination of P(V)porphyrins improved electron accepting ability. However, fluorination slightly suppressed static interaction with NADH, resulting in decreased oxidation quantum yield.

Differential responses of Mcl-1 in photosensitized epithelial vs lymphoid-derived human cancer cells.

PubMed

Xue, Liang-yan; Chiu, Song-mao; Oleinick, Nancy L

2005-10-20

The antiapoptotic Bcl-2-family proteins, Bcl-2 and Bcl-xL, are recognized phototargets of photodynamic therapy (PDT) with the mitochondrion-targeting phthalocyanine photosensitizer Pc 4. In the present study, we found that myeloid cell leukemia 1 (Mcl-1), another antiapoptotic member of the Bcl-2 family, was not photodamaged in Pc 4-PDT-treated human carcinoma cells MCF-7c3, MDA-MB468, DU145, and A431, although Mcl-1 turnover was observed after exposure of HeLa or MCF-7c3 cells to a supralethal dose of UVC. In contrast, when human lymphoma U937 and Jurkat cells were treated with Pc 4-PDT, staurosporine (STS) or UVC, Mcl-1 was cleaved to generate a 28-kDa fragment over a 2-4 h period. The cleavage of Mcl-1 was accompanied by the activation of caspases-3, -9, and -8. The broad-specificity caspase inhibitor z-VAD-fmk completely blocked Mcl-1 cleavage induced by PDT, STS or UVC, providing evidence for Mcl-1 as a substrate for caspases. Western blot analysis localized Mcl-1 to mitochondria, ER, and cytosol of both MCF-7c3 and U937 cells, suggesting that Mcl-1 protein, unlike Bcl-2 and Bcl-xL, is not a target for Pc 4-PDT, probably due to its localization to sites removed from those of Pc 4 binding. The 28-kDa cleaved fragment of Mcl-1, which has proapoptotic activity, was produced in PDT-treated lymphoid-derived cells, but not in cells of epithelial origin, suggesting that PDT-induced rapid and extensive apoptosis in lymphoma cells may result in part from the sensitivity of their Mcl-1 to caspase cleavage, removing an important negative control on apoptosis.

Sunlight-Dependent Hydrogen Production by Photosensitizer/Hydrogenase Systems.

PubMed

Adam, David; Bösche, Lisa; Castañeda-Losada, Leonardo; Winkler, Martin; Apfel, Ulf-Peter; Happe, Thomas

2017-03-09

We report a sustainable in vitro system for enzyme-based photohydrogen production. The [FeFe]-hydrogenase HydA1 from Chlamydomonas reinhardtii was tested for photohydrogen production as a proton-reducing catalyst in combination with eight different photosensitizers. Using the organic dye 5-carboxyeosin as a photosensitizer and plant-type ferredoxin PetF as an electron mediator, HydA1 achieves the highest light-driven turnover number (TON HydA1 ) yet reported for an enzyme-based in vitro system (2.9×10 6  mol(H 2 ) mol(cat) -1 ) and a maximum turnover frequency (TOF HydA1 ) of 550 mol(H 2 ) mol(HydA1) -1  s -1 . The system is fueled very effectively by ambient daylight and can be further simplified by using 5-carboxyeosin and HydA1 as a two-component photosensitizer/biocatalyst system without an additional redox mediator. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymer-Immobilized Photosensitizers for Continuous Eradication of Bacteria

PubMed Central

Valkov, Anton; Nakonechny, Faina; Nisnevitch, Marina

2014-01-01

The photosensitizers Rose Bengal (RB) and methylene blue (MB), when immobilized in polystyrene, were found to exhibit high antibacterial activity in a continuous regime. The photosensitizers were immobilized by dissolution in chloroform, together with polystyrene, with further evaporation of the solvent, yielding thin polymeric films. Shallow reservoirs, bottom-covered with these films, were used for constructing continuous-flow photoreactors for the eradication of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli and wastewater bacteria under illumination with visible white light using a luminescent lamp at a 1.8 mW·cm−2 fluence rate. The bacterial concentration decreased by two to five orders of magnitude in separate reactors with either immobilized RB or MB, as well as in three reactors connected in series, which contained one of the photosensitizers. Bacterial eradication reached more than five orders of magnitude in two reactors connected in series, where the first reactor contained immobilized RB and the second contained immobilized MB. PMID:25158236

Anchoring energy of photo-sensitive polyimide alignment film containing methoxy cinnamate

NASA Astrophysics Data System (ADS)

Kim, Suyoung; Shin, Sung Eui; Shin, DongMyung

2010-02-01

Photosensitive polyimide containing 2-methoxy cinnamate was synthesized for photo-alignment layer of liquid crystals (LCs). 2-Methoxy cinnamic acid was confirmed photo-sensitive material by linearly polarized UV light. We studied that effect of polarized UV light on rubbed polyimide film. Anchoring energy of liquid crystal with aligning surface was measured. Irradiation of depolarized UV light on rubbed Polyimide film suppressed effective anchoring energy. Linearly polarized UV light on rubbed polyimide film controlled anchoring energy effectively. Polyimide film containing 2-methoxy cinnamate can control the photo-alignment layer easily due to its photo-sensitivity.

Ru(II) dyads derived from 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline: versatile photosensitizers for photodynamic applications.

PubMed

Stephenson, Mat; Reichardt, Christian; Pinto, Mitch; Wächtler, Maria; Sainuddin, Tariq; Shi, Ge; Yin, Huimin; Monro, Susan; Sampson, Eric; Dietzek, Benjamin; McFarland, Sherri A

2014-11-13

Combining the best attributes of organic photosensitizers with those of coordination complexes is an elegant way to achieve prolonged excited state lifetimes in Ru(II) dyads. Not only do their reduced radiative and nonradiative rates provide ample time for photosensitization of reactive oxygen species at low oxygen tension but they also harness the unique properties of (3)IL states that can act as discrete units or in concert with (3)MLCT states. The imidazo[4,5-f][1,10]phenanthroline framework provides a convenient tether for linking π-expansive ligands such as pyrene to a Ru(II) scaffold, and the stabilizing coligands can fine-tune the chemical and biological properties of these bichromophoric systems. The resulting dyads described in this study exhibited nanomolar light cytotoxicities against cancer cells with photocytotoxicity indices exceeding 400 for some coligands employed. This potency extended to bacteria, where concentrations as low as 10 nM destroyed 75% of a bacterial population. Notably, these dyads remained extremely active against biofilm with light photocytotoxicities against these more resistant bacterial populations in the 10-100 nM regime. The results from this study demonstrate the versatility of these highly potent photosensitizers in destroying both cancer and bacterial cells and expand the scope of compounds that utilize low-lying (3)IL states for photobiological applications.

Laser inactivation of periodontal bacteria using photosensitizing dyes

NASA Astrophysics Data System (ADS)

Golding, Paul S.; Maddocks, L.; King, Terence A.; Drucker, D. B.

1996-12-01

We demonstrate the killing of the oral bacteria Prevotella nigrescens using a photosensitizer and light from a 10 Hz, frequency doubled, Q-switched Nd:YAG pumped dye laser, with modified oscillator to increase output power. This system produced light at wavelengths close to 620 nm, the absorption maximum of the photosensitizing agent, malachite green isothiocyanate, a wavelength that is not significantly absorbed by tissue. A bacterial reduction of 97.5 percent was achieved at an energy density of 0.67 J/cm2 and exposure times of 300 seconds.

Novel approach to the microbial decontamination of strawberries: chlorophyllin-based photosensitization.

PubMed

Luksiene, Z; Paskeviciute, E

2011-05-01

This study is focused on the possibility to control microbial contamination of strawberries by chlorophyllin (Na-Chl)-based photosensitization. Moreover, photosensitization-induced effects on key quality attributes of treated strawberries was evaluated.   Strawberries were inoculated with Listeria monocytogenes ATC(L3) C 7644, soaked in 1mmol l(-1) Na-Chl for 5 min and illuminated for 30 min with visible light (λ = 400 nm, energy density 12 mW cm(-2) ). Results indicated that the decontamination of strawberries using photosensitization was 98% compared to control sample. Naturally occurring yeasts/microfungi and mesophiles were inhibited by 86 and 97%, respectively. The shelf life of treated strawberries was extended by 2 days. The total antioxidant activity of treated strawberries increased by 19%. No impact on the amount of phenols, anthocyanins or surface colour was detected.   Photosensitization may be an effective, nonthermal and environmentally friendly microbial decontamination technique which expands the shelf life of strawberries without any negative impact on antioxidant activity, and phenols, anthocyanins or colour formation. Experimental data support the idea that Na-Chl-based photosensitization can be a useful tool for the future development of nonthermal food preservation technology. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

Experimental photodynamic laser therapy for rheumatoid arthritis with a second generation photosensitizer.

PubMed

Hendrich, C; Hüttmann, G; Vispo-Seara, J L; Houserek, S; Siebert, W E

2000-01-01

Photodynamic laser therapy has been shown to be a new method for the treatment of synovitis in various animal models. Its principle is the accumulation of a photosensitizing drug in the inflamed synovium which is destroyed by photoactivation of the drug. In the present animal study we demonstrate the effect of a second-generation photosensitizer and suggest a concept for light dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced arthritis model; 2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD-MA) Verteporfin were administered 3 h before irradiation, which was performed using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffusor tip at a total light energy of either 180 or 470 J. During irradiation specific fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the photodynamic laser therapy was documented grossly and histologically after 1 week. Within the 470 J-group a complete necrosis of the inflamed synovium was observed. The bradytrophic structures of the joint, however, remained unchanged. Throughout the 180 J-group the extent of necrosis was minor. During irradiation the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA as a photosensitizer a highly selective and minimal invasive synoviorthesis can be performed. At a dose of 2 mg/kg the histological effect depends on the light dose. For optimum efficacy a total energy of 470 J seems favorable. Online fluorescence detection can be used to monitor the effect of light administration. For dosimetry therefore an online tissue fluorescence detection may represent a technical solution.

Fundamental study on photodynamic therapy for atrial fibrillation: effect of photosensitization reaction parameters on myocardial necrosis in vitro

NASA Astrophysics Data System (ADS)

Ogawa, Emiyu; Ito, Arisa; Arai, Tsunenori

2012-03-01

We studied necrotic cell death effect on myocardial cells with photosensitizer existed outside the cells varying photosensitization reaction parameters widely in vitro. We have developed non-thermal ablator with the application of photosensitization reaction for atrial fibrillation. Since laser irradiation is applied shortly after photosensitizer injection, the photosensitization reaction is induced outside the cells. The interaction for the myocardial cells by the photosensitization reaction is not well understood yet on various photosensitization reaction parameters. Rat myocardial cells were cultured in 96 well plates for 7 days. The photosensitization reaction was applied with talaporfin sodium (NPe6) and the semiconductor laser of 663nm wavelength. The average drug light interval was set 8 mins. The photosensitizer concentration and radiant exposure were varied from 5 to 40 μg/ml and 1.2 to 60 J/cm2, respectively. The well bottom was irradiated by the red laser with irradiance of 293 mW/cm2. The photosensitizer fluorescence was monitored during the photosensitization reaction. Alive cell rate was measured by WST assay after 2 hours from the irradiation. In the case of the photosensitizer concentration of 10 μg/ml, the myocardial cells were almost alive even thought 60 J/cm2 in the radiant exposure was applied. In the 15 μg/ml case, the alive cell rate was almost linear relation to the photosensitizer concentration and radiant exposure. We obtained that the threshold for myocardial cell necrosis on the photosensitizer concentration was around 15 μg/ml with 20 J/cm2 in the radiant exposure. This threshold on the photosensitizer concentration was similar to the reported threshold for cancer therapy.

In vivo photoacoustic monitoring of photosensitizer in skin: application to dosimetry for antibacterial photodynamic treatment

NASA Astrophysics Data System (ADS)

Hirao, Akihiro; Sato, Shunichi; Saitoh, Daizoh; Shinomiya, Nariyoshi; Ashida, Hiroshi; Obara, Minoru

2009-02-01

To obtain efficient antibacterial photodynamic effect in traumatic injuries such as burns, depth-resolved dosimetry of photosensitizer is required. In this study, we performed dual-wavelength photoacoustic (PA) measurement for rat burned skins injected with a photosensitizer. As a photosensitizer, methylene blue (MB) or porfimer sodium was injected into the subcutaneous tissue in rats with deep dermal burn. The wound was irradiated with red (665 nm or 630 nm) pulsed light to excite photosensitizers and green (532 nm) pulsed light to excite blood in the tissue; the latter signal was used to eliminate blood-associated component involved in the former signal. Acoustic attenuation was also compensated from the photosensitizer-associated PA signals. These signal processing was effective to obtain high-contrast image of a photosensitizer in the tissue. Behaviors of MB and porfimer sodium in the tissue were compared.

Photosensitized oxidation of nicotinamide adenine dinucleotide by diethoxyphosphorus(V)tetraphenylporphyrin and its fluorinated derivative: Possibility of chain reaction.

PubMed

Hirakawa, Kazutaka; Murata, Atsushi

2018-01-05

Water-soluble porphyrins, diethoxyphosphorus(V)tetraphenylporphyrin (EtP(V)TPP) and its fluorinated analogue (FEtP(V)TPP), decreased the typical absorption around 340nm of nicotinamide adenine dinucleotide (NADH) under visible light irradiation, indicating oxidative decomposition. A singlet oxygen quencher, sodium azide, and a triplet quencher, potassium iodide, slightly inhibited photosensitized NADH oxidation. However, these inhibitory effects were very small. Furthermore, the fluorescence lifetime of these P(V)porphyrins was decreased by NADH, suggesting the contribution of electron transfer to the singlet excited (S 1 ) state of P(V)porphyrin. The redox potential measurement supports the electron transfer-mediated oxidation of NADH. The quantum yields of NADH photodecomposition by P(V)porphyrins could be estimated from the kinetic data and the effect of these quenchers on NADH oxidation. The obtained values suggest that the electron accepting by the S 1 states of P(V)porphyrins triggers a chain reaction of NADH oxidation. This photosensitized reaction may play an important role in the photocytotoxicity of P(V)porphyrins. The axial ligand fluorination of P(V)porphyrins improved electron accepting ability. However, fluorination slightly suppressed static interaction with NADH, resulting in decreased oxidation quantum yield. Copyright © 2017 Elsevier B.V. All rights reserved.

In-vitro singlet oxygen threshold dose at PDT with Radachlorin photosensitizer

NASA Astrophysics Data System (ADS)

Klimenko, V. V.; Shmakov, S. V.; Kaydanov, N. E.; Knyazev, N. A.; Kazakov, N. V.; Rusanov, A. A.; Bogdanov, A. A.; Dubina, M. V.

2017-07-01

In this present study we investigate the Radachlorin photosensitizer accumulation in K562 cells and Hela cells and determined the cell viability after PDT. Using the macroscopic singlet oxygen modeling and cellular photosensitizer concentration the singlet oxygen threshold doses for K562 cells and Hela cells were calculated.

3-D photo-patterning of refractive index structures in photosensitive thin film materials

DOEpatents

Potter, Jr., Barrett George; Potter, Kelly Simmons

2002-01-01

A method of making a three-dimensional refractive index structure in a photosensitive material using photo-patterning. The wavelengths at which a photosensitive material exhibits a change in refractive index upon exposure to optical radiation is first determined and then a portion of the surface of the photosensitive material is optically irradiated at a wavelength at which the photosensitive material exhibits a change in refractive index using a designed illumination system to produce a three-dimensional refractive index structure. The illumination system can be a micro-lenslet array, a macroscopic refractive lens array, or a binary optic phase mask. The method is a single-step, direct-write procedure to produce a designed refractive index structure.

[Spectral properties of new photosensitizers for photodynamic diagnosis and therapy].

PubMed

Li, Bu-hong; Xie, Shu-sen; Lu, Zu-kang

2002-12-01

The spectral properties of new photosensitizer ZnPcS2P2, PsD-007 and HMME, as well as traditional photosensitizer HpD have been studied by comparing their spectra in physiological saline and in physiological saline with 10 percent serum. Experimental results show that the maximum absorption peaks for PsD-007, HMME and HpD in the physiological saline with 10 percent serum appear at 400 nm in the soret region, while at 670 nm for ZnPcS2P2. The fluorescence excitation spectra closely resemble the absorption spectra. When excited by the light at the wavelengths of 413 and 514.5 nm, the fluorescence emission peaks for PsD-007, HMME and HpD appear at 625 and 690 nm, respectively. The fluorescent excitation efficiency of the same photosensitizer with the same concentration excited by the light at the wavelength of 413 nm is about three fold higher than that at 514.5 nm. Furthermore, the fluorescent excitation efficiency is the highest for HMME, but is lower for HpD and lowest for PsD-007. These results are significant in the selection of photosensitizers for photodynamic diagnosis and therapy.

Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization.

PubMed

Matroule, J Y; Carthy, C M; Granville, D J; Jolois, O; Hunt, D W; Piette, J

2001-07-05

Pyropheophorbide-a methylester (PPME) is a second generation of photosensitizers used in photodynamic therapy (PDT). We demonstrated that PPME photosensitization triggered apoptosis of colon cancer cells as measured by using several classical parameters such as DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c. Preincubation of cells with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protected against apoptosis mediated by PPME photosensitization showing that reactive oxygen species (ROS) are involved as second messengers. On the other hand, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (1O2) lifetime only increases necrosis without affecting apoptosis. Since PPME was localized in the endoplasmic reticulum (ER)/Golgi system and lysosomes, other messengers than ROS were tested such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c release from mitochondria. On the other hand, we demonstrated that the transduction pathways leading to NF-kappaB activation and apoptosis were clearly independent although NF-kappaB was shown to counteract apoptosis mediated by PPME photosensitization.

Phosphorescence Kinetics of Singlet Oxygen Produced by Photosensitization in Spherical Nanoparticles. Part I. Theory.

PubMed

Hovan, Andrej; Datta, Shubhashis; Kruglik, Sergei G; Jancura, Daniel; Miskovsky, Pavol; Bánó, Gregor

2018-05-24

The singlet oxygen produced by energy transfer between an excited photosensitizer (pts) and ground-state oxygen molecules plays a key role in photodynamic therapy. Different nanocarrier systems are extensively studied to promote targeted pts delivery in a host body. The phosphorescence kinetics of the singlet oxygen produced by the short laser pulse photosensitization of pts inside nanoparticles is influenced by singlet oxygen diffusion from the particles to the surrounding medium. Two theoretical models are presented in this work: a more complex numerical one and a simple analytical one. Both the models predict the time course of singlet oxygen concentration inside and outside of the spherical particles following short-pulse excitation of pts. On the basis of the comparison of the numerical and analytical results, a semiempirical analytical formula is derived to calculate the characteristic diffusion time of singlet oxygen from the nanoparticles to the surrounding solvent. The phosphorescence intensity of singlet oxygen produced in pts-loaded nanocarrier systems can be calculated as a linear combination of the two concentrations (inside and outside the particles), taking the different phosphorescence emission rate constants into account.

Permeability of DOPC bilayers under photoinduced oxidation: Sensitivity to photosensitizer.

PubMed

Bacellar, Isabel O L; Baptista, Mauricio S; Junqueira, Helena C; Wainwright, Mark; Thalmann, Fabrice; Marques, Carlos M; Schroder, André P

2018-06-07

The modification of lipid bilayer permeability is one of the most striking yet poorly understood physical transformations that follow photoinduced lipid oxidation. We have recently proposed that the increase of permeability of photooxidized 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers is controlled by the time required by the oxidized lipid species to diffuse and aggregate into pores. Here we further probe this mechanism by studying photosensitization of DOPC membranes by methylene blue (MB) and DO15, a more hydrophobic phenothiazinium photosensitizer, under different irradiation powers. Our results not only reveal the interplay between the production rate and the diffusion of the oxidized lipids, but highlight also the importance of photosensitizer localization in the kinetics of oxidized membrane permeability. Copyright © 2018. Published by Elsevier B.V.

Smart Photosensitizer: Tumor-Triggered Oncotherapy by Self-Assembly Photodynamic Nanodots.

PubMed

Jia, Yuhua; Li, Jinyu; Chen, Jincan; Hu, Ping; Jiang, Longguang; Chen, Xueyuan; Huang, Mingdong; Chen, Zhuo; Xu, Peng

2018-05-09

Clinical photosensitizers suffer from the disadvantages of fast photobleaching and high systemic toxicities because of the off-target photodynamic effects. To address these problems, we report a self-assembled pentalysine-phthalocyanine assembly nanodots (PPAN) fabricated by an amphipathic photosensitizer-peptide conjugate. We triggered the photodynamic therapy effects of photosensitizers by precisely controlling the assembly and disintegration of the nanodots. In physiological aqueous conditions, PPAN exhibited a size-tunable spherical conformation with a highly positive shell of the polypeptides and a hydrophobic core of the π-stacking Pc moieties. The assembly conformation suppressed the fluorescence and the reactive oxygen species generation of the monomeric photosensitizer molecules (mono-Pc) and thus declined the photobleaching and off-target photodynamic effects. However, tumor cells disintegrated PPAN and released the mono-Pc molecules, which exhibited fluorescence for detection and the photodynamic effects for the elimination of the tumor tissues. The molecular dynamics simulations revealed the various assembly configurations of PPAN and illustrated the assembly mechanism. At the cellular level, PPAN exhibited a remarkable phototoxicity to breast cancer cells with the IC 50 values in a low nanomolar range. By using the subcutaneous and orthotopic breast cancer animal models, we also demonstrated the excellent antitumor efficacies of PPAN in vivo.

Spatial photosensitizer fluorescence emission predictive analysis for photodynamic therapy monitoring applied to a skin disease

NASA Astrophysics Data System (ADS)

Salas-García, Irene; Fanjul-Vélez, Félix; Arce-Diego, José Luis

2012-03-01

The development of Photodynamic Therapy (PDT) predictive models has become a valuable tool for an optimal treatment planning, monitoring and dosimetry adjustment. A few attempts have achieved a quite complete characterization of the complex photochemical and photophysical processes involved, even taking into account superficial fluorescence in the target tissue. The present work is devoted to the application of a predictive PDT model to obtain fluorescence tomography information during PDT when applied to a skin disease. The model takes into account the optical radiation distribution, a non-homogeneous topical photosensitizer distribution, the time dependent photochemical interaction and the photosensitizer fluorescence emission. The results show the spatial evolution of the photosensitizer fluorescence emission and the amount of singlet oxygen produced during PDT. The depth dependent photosensitizer fluorescence emission obtained is essential to estimate the spatial photosensitizer concentration and its degradation due to photobleaching. As a consequence the proposed approach could be used to predict the photosensitizer fluorescence tomographic measurements during PDT. The singlet oxygen prediction could also be employed as a valuable tool to predict the short term treatment outcome.

Off-Resonance Photosensitization of a Photorefractive Polymer Composite Using PbS Nanocrystals

DOE PAGES

Moon, Jong-Sik; Liang, Yichen; Stevens, Tyler E.; ...

2015-05-26

The photosensitization of photorefractive polymeric composites for operation at 633 nm is accomplished through the inclusion of narrow band gap semiconductor nanocrystals composed of PbS. Unlike previous studies involving photosensitization of photorefractive polymer composites with inorganic nanocrystals, we employ an off-resonance approach where the first excitonic transition associated with the PbS nanocrystals lies at ~1220 nm and not the wavelength of operation. Using this methodology, internal diffraction efficiencies exceeding 82%, two-beam-coupling gain coefficients of 211 cm –1, and response times of 34 ms have been observed, representing some of the best figures of merit reported for this class of materials.more » Furthermore, these data demonstrate the ability of semiconductor nanocrystals to compete effectively with traditional organic photosensitizers. In addition to superior performance, this approach also offers an inexpensive and easy means by which to photosensitize composite materials. Additionally, the photoconductive characteristics of the composites used for this study will also be considered.« less

The role of the peripheral benzodiazepine receptor in photodynamic activity of certain pyropheophorbide ether photosensitizers: albumin site II as a surrogate marker for activity.

PubMed

Dougherty, Thomas J; Sumlin, Adam B; Greco, William R; Weishaupt, Kenneth R; Vaughan, Lurine A; Pandey, Ravindra K

2002-07-01

A study has been carried out to define the importance of the peripheral benzodiazepine receptor (PBR) as a binding site for a series of chlorin-type photosensitizers, pyropheophorbide-a ethers, the subject of a previous quantitative structure-activity relationship study by us. The effects of the PBR ligand PK11195 on the photodynamic activity have been determined in vivo for certain members of this series of alkyl-substituted ethers: two of the most active derivatives (hexyl and heptyl), the least active derivative (dodecyl [C12]) and one of intermediate activity (octyl [C8]). The photodynamic therapy (PDT) effect was inhibited by PK11195 for both of the most active derivatives, but no effect on PDT activity was found for the less active C12 or C8 ethers. The inhibitory effects of PK11195 were predicted by the binding of only the active derivatives to the benzodiazepine site on albumin, ie. human serum albumin (HSA)-Site II. Thus, as with certain other types of photosensitizers, it has been demonstrated with this series of pyropheophorbide ethers that in vitro binding to HSA-Site II is a predictor of both optimal in vivo activity and binding to the PBR in vivo.

Phosphorescence dynamics of singlet oxygen and Radachlorin photosensitizer in aqueous solution

NASA Astrophysics Data System (ADS)

Belik, V. P.; Beltukova, D. M.; Gadzhiev, I. M.; Semenova, I. V.; Vasyutinskii, O. S.

2017-07-01

The luminescence spectrum of aqueous solution of Radachlorin photosensitizer in the near IR spectral range (950-1350 nm) has been determined at the excitation in both the Soret and Q absorption bands. Major sources of the recorded luminescence were analyzed. Kinetics of photosensitizer and singlet oxygen phosphorescence signals were studied by means of time-resolved spectroscopy. The corresponding characteristic lifetimes were determined.

[Comparative toxicity of photosensitizers in varying destruction].

PubMed

Sinitsina, O O; Zholdakova, Z I; Poliakova, E E; Golovach, E N; Sycheva, L P; Beliaeva, N N; Kuznetsova, N A

2007-01-01

The toxicity of the photosensitizers proflavine acetate (PA) versus methylene blue (MB) was evaluated during their varying destruction. Under the influence of visible light, a partial (25%) transformation of the photosensitizers was shown to be attended by their enhanced toxicity and 100% destruction of the parent substances caused a reduction in their hazard. PA and its phototransformation products mainly affect the antiperoxide protection system and the structural and functional states of the liver, kidney, and duodenum. The maximum noneffective dose is 0.002 mg/kg. The possibility of using PA for water disinfection depends on the ratio of safe and effective concentrations. A partial (25%) MB destruction products cause mutagenic effects; the permissible dose of the mutagen is 0.00025 mg/kg. MB is not recommended for disinfection of all types of waters.

Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks

PubMed Central

Vaudano, Anna Elisabetta; Ruggieri, Andrea; Avanzini, Pietro; Gessaroli, Giuliana; Cantalupo, Gaetano; Coppola, Antonietta; Sisodiya, Sanjay M.

2017-01-01

Abstract See Hamandi (doi:10.1093/awx049) for a scientific commentary on this article. Photosensitivity is a condition in which lights induce epileptiform activities. This abnormal electroencephalographic response has been associated with hyperexcitability of the visuo-motor system. Here, we evaluate if intrinsic dysfunction of this network is present in brain activity at rest, independently of any stimulus and of any paroxysmal electroencephalographic activity. To address this issue, we investigated the haemodynamic correlates of the spontaneous alpha rhythm, which is considered the hallmark of the brain resting state, in photosensitive patients and in people without photosensitivity. Second, we evaluated the whole-brain functional connectivity of the visual thalamic nuclei in the various populations of subjects under investigation. Forty-four patients with epilepsy and 16 healthy control subjects underwent an electroencephalography-correlated functional magnetic resonance imaging study, during an eyes-closed condition. The following patient groups were included: (i) genetic generalized epilepsy with photosensitivity, 16 subjects (mean age 25 ± 10 years); (ii) genetic generalized epilepsy without photosensitivity, 13 patients (mean age 25 ± 11 years); (iii) focal epilepsy, 15 patients (mean age 25 ± 9 years). For each subject, the posterior alpha power variations were convolved with the standard haemodynamic response function and used as a regressor. Within- and between-groups second level analyses were performed. Whole brain functional connectivity was evaluated for two thalamic regions of interest, based on the haemodynamic findings, which included the posterior thalamus (pulvinar) and the medio-dorsal thalamic nuclei. Genetic generalized epilepsy with photosensitivity demonstrated significantly greater mean alpha-power with respect to controls and other epilepsy groups. In photosensitive epilepsy, alpha-related blood oxygen level-dependent signal changes

Tetrapyrrole-photosensitizers vectorization and plasma LDL: a physico-chemical approach.

PubMed

Bonneau, Stéphanie; Vever-Bizet, Christine; Mojzisova, Halina; Brault, Daniel

2007-11-01

A photosensitizer is defined as a chemical entity able to induce, under light-irradiation effect, a chemical or physical alteration of another chemical entity. Thanks to their preferential retention in proliferating tissues, some photosensitizers are therapeutically used such as in photodynamic therapy (PDT). Besides, this method has already been approved for several indications. The selectivity of photosenzitizers for cells in proliferation involves both their association with low density lipoproteins (LDLs) and their ability to cross membranes under various pH conditions. The photosensitizers used are in most cases based on the porphyrin structure, but other compounds, of which far-red-light absorption properties are most compatible with biological tissues irradiation, have been developed, such as phthalocyanines. This paper presents physico-chemical studies of the interaction of a disulfonated aluminium phthalocyanine (AlPcS2) with human LDLs. The data obtained are compared with the parameters of the interaction of these lipoproteins with deuteroporphyrin (DP) and chlorin e6 (Ce6). A close attention is paid to the dynamic aspects of these phenomena. The data obtained on these simple systems then allowed us to interpret the sub-cellular localization of the photosensitizers on a human line of fibroblasts, and to evaluate the influence of LDLs on the intracellular distribution of the compounds. This last point is of major importance because the localization of such photosensitizers (in particular AlPcS2) in endocytic vesicles and their subsequent ability to induce a release of the contents of these vesicles - including externally added macromolecules - into the cytosol is the basis for a recent method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules. The comprehension of the mechanisms governing this particular sub-cellular localization could allow

Mini review on photosensitization by plants in grazing herbivores.

PubMed

Hussain, Syeda M; Herling, Valdo Rodrigues; Rodrigues, Paulo Henrique Mazza; Naz, Ishrat; Khan, Hamayun; Khan, Muhammad Tahir

2018-06-01

Photosensitization is severe dermatitis or oxidative/chemical changes in the epidermal tissues activated by the light-induced excitation of molecules within the tissue. It is a series of reactions mediated through light receptors and is more common when the plant-produced metabolites are heterocyclic/polyphenols in nature. The areas affected are exposed body parts and mostly non-pigmented areas with least ultraviolet protection. Similarly, cellular alteration also occurs in the affected animal's dermal tissues and body parts and grazing animals by the accumulation and activation of photodynamic molecules. Photo-oxidation can also occur within the plant due to the generation of reactive oxygen species causing damage and degradation in the form of free radicals and DNA. During the last few decades, many new tropical grass species have been introduced in the grazing lands which are genetically modified, and the animals grazing on them are facing various forms of toxicity including photosensitization. The plant's secondary metabolites/drugs may cause toxicity when bacteria, viral agents, fungi (Pithomyces chartarum), or neoplasia injures the liver and prevents the phylloerythrin excretion. All these may disturb the liver enzymes and blood profile causing a decrease in weight and production (wool and milk etc.) with severe dermal, digestive, and nervous problems. Recent advancements in OMICS (cellomics, ethomics, metabolomics, metabonomics, and glycomics) have enabled us to detect and identify the plants' secondary metabolites and changes in the animal's physiology and histopathology as a causative of photosensitivity. The review focuses on types of photosensitization, reasons, secondary metabolic compounds, chemistry, and environmental effect on plants.

Analysis of photodynamic therapy applied to skin disorders by a topical photosensitizer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Romanov, O. G.; López-Escobar, M.; Rodriguez-Colmenares, M. A.; Ortega-Quijano, N.; Arce-Diego, J. L.

2008-11-01

Optical treatment of pathological tissues comprises techniques like Low Intensity Laser Treatment (LILT) or Photodynamic Therapy (PDT). PDT consists on the inoculation of a photosensitizer in the tissue, which tends to be accumulated in cancerous cells, and on the posterior optical radiation of the area. The photosensitizer, that can be topical or systemic, is excited and cell necrosis is provoked. The collateral harmful effects of other destructive techniques, like radiotherapy or chemotherapy, are avoided with PDT. PDT can also be used as a complementary technique of conventional excisional surgical operations. The application of PDT to skin disorders is straightforward due to the fact that it is an external and accessible tissue. In this work, we analyze the application of PDT to several skin pathologies and the results obtained, by means of mainly the usage of MetvixR as a topical photosensitizer and with an optical source in the range of 635 nm. The analysis includes a predictive model of the PDT process, based on an optical propagation equation and a photosensitizer degradation approach that provides an estimation of tissue destruction.

Time-resolved luminescence measurements of the magnetic field effect on paramagnetic photosensitizers in photodynamic reactions

NASA Astrophysics Data System (ADS)

Mermut, O.; Bouchard, J.-P.; Cormier, J.-F.; Desroches, P.; Diamond, K. R.; Fortin, M.; Gallant, P.; Leclair, S.; Marois, J.-S.; Noiseux, I.; Morin, J.-F.; Patterson, M. S.; Vernon, M.

2008-02-01

The development of multimodal molecular probes and photosensitizing agents for use in photodynamic therapy (PDT) is vital for optimizing and monitoring cytotoxic responses. We propose a combinatorial approach utilizing photosensitizing molecules that are both paramagnetic and luminescent with multimodal functionality to perturb, control, and monitor molecular-scale reaction pathways in PDT. To this end, a time-domain single photon counting lifetime apparatus with a 400 nm excitation source has been developed and integrated with a variable low field magnet (0- 350mT). The luminescence lifetime decay function was measured in the presence of a sweeping magnetic field for a custom designed photosensitizing molecule in which photoinduced electron transfer was studied The photosensitizer studied was a donor-acceptor complex synthesized using a porphyrin linked to a fullerene molecule. The magneto-optic properties were investigated for the free-base photosensitizer complex as well as those containing either diamagnetic (paired electron) or paramagnetic (unpaired electron) metal centers, Zn(II) and Cu(II). The magnetic field was employed to affect and modify the spin states of radical pairs of the photosensitizing agents via magnetically induced hyperfine and Zeeman effects. Since the Type 1 reaction pathway of an excited triplet state photosensitizer involves the production of radical species, lifetime measurements were conducted at low dissolved oxygen concentration (0.01ppm) to elucidate the dependence of the magnetic perturbation on the photosensitization mechanistic pathway. To optimize the magnetic response, a solvent study was performed examining the dependence of the emission properties on the magnetic field in solutions of varying dielectric constants. Lastly, the cytotoxicity in murine tumor cell suspensions was investigated for the novel porphyrin-fullerene complex by inducing photodynamic treatments and determining the associated cell survival.

Hematopoietic stimulation by porphyrin photosensitizers (Invited Paper)

NASA Astrophysics Data System (ADS)

Levy, Julia G.; Hunt, David W. C.; Mitchell, David W.; Jamieson, Catriona H. M.

1992-06-01

The effects of the photosensitizers, PhotofrinTM and benozoporphyrin derivative monoacid ring A (BPD) on a variety of hematopoietic cell functions have been studied, both in the presence and absence of light activation. A marked increase in hematopoiesis was observed in the bone marrow and spleens of DBA/2 mice administered high dose Photofrin but not BPD. This was manifested in an increased relative spleen weight, nucleated spleen cell number and circulating white blood cell concentration 7 days following Photofrin injection. We have shown that BPD and light doses just below phototoxic ranges stimulate the growth of human colony forming committed myeloid progenitors as well as pluripotent stem cells grown in long term marrow culture. Studies on the effect of BPD on the function of T lymphocytes in the absence of light has also demonstrated a stimulatory effect. The dose range in which this is observed is considerably broader than that observed with light activation. The mechanisms involved in this stimulatory effect have been studied and are discussed.

Modified developer increases line resolution in photosensitive resist

NASA Technical Reports Server (NTRS)

1965-01-01

Standard developer solution is mixed with dipropyl carbonate. This reduces swelling in the photosensitive resist and permits application of relatively thick films with minimal pinhole formation and increased line resolution.

Extended rhodamine photosensitizers for photodynamic therapy of cancer cells.

PubMed

Davies, Kellie S; Linder, Michelle K; Kryman, Mark W; Detty, Michael R

2016-09-01

Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M). Copyright © 2016 Elsevier Ltd. All rights reserved.

The (6-4) Dimeric Lesion as a DNA Photosensitizer.

PubMed

Vendrell-Criado, Victoria; Rodríguez-Muñiz, Gemma M; Lhiaubet-Vallet, Virginie; Cuquerella, M Consuelo; Miranda, Miguel A

2016-07-04

Based on our previous investigations into the photophysical properties of the 5-methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1) , and a triplet-excited-state energy of 297 kJ mol(-1) . Its triplet transient absorption has a maximum at 420-440 nm, a lifetime of around 7 μs, and a high formation quantum yield, ΦISC =0.86. This species is efficiently quenched by thymidine. Its DNA photosensitizing properties are demonstrated by a series of experiments run on a pBR322 plasmid. The lesion photoinduces both single-strand breaks and the formation of cyclobutane thymine dimers. Altogether, these results show that, the substitution of the pyrimidone ring at C4 by a 5-hydroxy-5,6-dihydrothymine does not cancel out the photosensitization properties of the chromophore. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-dimensional singlet oxygen imaging with its near-infrared luminescence during photosensitization

PubMed Central

Hu, Bolin; Zeng, Nan; Liu, Zhiyi; Ji, Yanhong; Xie, Weidong; Peng, Qing; Zhou, Yong; He, Yonghong; Ma, Hui

2011-01-01

Photodynamic therapy is a promising cancer treatment that involves activation of photosensitizer by visible light to create singlet oxygen. This highly reactive oxygen species is believed to induce cell death and tissue destruction in PDT. Our approach used a near-infrared area CCD with high quantum efficiency to detect singlet oxygen by its 1270-nm luminescence. Two-dimensional singlet oxygen images with its near-infrared luminescence during photosensitization could be obtained with a CCD integration time of 1 s, without scanning. Thus this system can produce singlet oxygen luminescence images faster and achieve more accurate measurements in comparison to raster-scanning methods. The experimental data show a linear relationship between the singlet oxygen luminescence intensity and sample concentration. This method provides a detection sensitivity of 0.0181 μg/ml (benzoporphyrin derivative monoacid ring A dissolved in ethanol) and a spatial resolution better than 50 μm. A pilot study was conducted on a total of six female Kunming mice. The results from this study demonstrate the system's potential for in vivo measurements. Further experiments were carried out on two tumor-bearing nude mice. Singlet oxygen luminescence images were acquired from the tumor-bearing nude mouse with intravenous injection of BPD-MA, and the experimental results showed real-time singlet oxygen signal depletion as a function of the light exposure. PMID:21280909

A palladium label to monitor nanoparticle-assisted drug delivery of a photosensitizer into tumor spheroids by elemental bioimaging.

PubMed

Niehoff, Ann-Christin; Moosmann, Aline; Söbbing, Judith; Wiehe, Arno; Mulac, Dennis; Wehe, Christoph A; Reifschneider, Olga; Blaske, Franziska; Wagner, Sylvia; Sperling, Michael; von Briesen, Hagen; Langer, Klaus; Karst, Uwe

2014-01-01

In this study, the cellular uptake of the second generation photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) was investigated using laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP-MS) at a spatial resolution of 10 μm. To achieve high sensitivity, the photosensitizer was tagged with palladium. As a tumor model system, a 3D cell culture of the TKF-1 cell line was used. These tumor spheroids were incubated with the Pd-tagged photosensitizer embedded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles to investigate the efficiency of nanoparticle based drug delivery. An accumulation of the drug in the first cell layers of the tumor spheroid was observed. In the case of nanoparticle based drug delivery, a significantly more homogeneous distribution of the photosensitizer was achieved, compared to tumor spheroids incubated with the dissolved photosensitizer without the nanoparticular drug delivery system. The infiltration depth of the Pd-tagged photosensitizer could not be increased with rising incubation time, which can be attributed to the adsorption of the photosensitizer onto cellular components.

Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production

NASA Astrophysics Data System (ADS)

Sugita, Kazunari; Ikenouchi-Sugita, Atsuko; Nakayama, Yasuko; Yoshioka, Haruna; Nomura, Takashi; Sakabe, Jun-Ichi; Nakahigashi, Kyoko; Kuroda, Etsushi; Uematsu, Satoshi; Nakamura, Jun; Akira, Shizuo; Nakamura, Motonobu; Narumiya, Shuh; Miyachi, Yoshiki; Tokura, Yoshiki; Kabashima, Kenji

2013-10-01

Pellagra is a photosensitivity syndrome characterized by three ``D's'': diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation.

Uptake of photosensitizers by bacteria is influenced by the presence of cations

NASA Astrophysics Data System (ADS)

Kishen, A.; George, S.

2007-05-01

This investigation studies the influence of cations on photosensitizer uptake by Enterococcus faecalis (gram positive) and Actinobacillus actinomycetemcomitans (gram negative). Methods- The uptake of Methylene blue (MB) and Indocyanine Green (ICG), by bacteria were studied under the influence of divalent cations (CaCl II & MgCl II) and EDTA. Further, E. faecalis cells subjected to trypsinisation and calcium channel blocker (verapamil) were also analysed for MB and ICG uptake inorder to understand the mechanism of photosensitizer uptake. Results- Uptake of ICG was enhanced in the presence of divalent cations in E. faecalis and A. actinomycetemcomitans. Treating cells with EDTA had no significant effect on the photosensitizer uptake, although the highest concentration tested showed an enhancement of uptake. In contrast to ICG, MB showed a decreased uptake by bacterial cells on subjecting them to divalent cations and EDTA. Calcium channel blocker had no significant inhibitory effect on photosensitizers uptake. However, trypsin treatment resulted in significant reduction of ICG uptake. The result suggested that ICG uptake by bacteria is mediated through specific transporter protein while MB is associated with the outer surface structures of bacterial cells.

How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?

PubMed

Yuen, Eunice S M; Sims, John R

2014-06-01

Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature. A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically. The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51). Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions

NASA Astrophysics Data System (ADS)

Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

2012-02-01

Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 μL/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

Inactivation of Bacillus cereus by Na-chlorophyllin-based photosensitization on the surface of packaging.

PubMed

Luksiene, Z; Buchovec, I; Paskeviciute, E

2010-11-01

This study was focused on the possibility to inactivate food-borne pathogen Bacillus cereus by Na-chlorophyllin (Na-Chl)-based photosensitization in vitro and after attachment to the surface of packaging material. Bacillus cereus in vitro or attached to the packaging was incubated with Na-Chl (7·5×10(-8) to 7·5×10(-5) mol l(-1) ) for 2-60min in phosphate buffer saline. Photosensitization was performed by illuminating cells under a light with a λ of 400nm and an energy density of 20mW cm(-2) . The illumination time varied 0-5min and subsequently the total energy dose was 0-6J cm(-2) . The results show that B. cereus vegetative cells in vitro or attached to the surface of packaging after incubation with 7·5×10(-7) mol l(-1) Na-Chl and following illumination were inactivated by 7log. The photoinactivation of B. cereus spores in vitro by 4log required higher (7·5×10(-6) mol l(-1) ) Na-Chl concentration. Decontamination of packaging material from attached spores by photosensitization reached 5log at 7·5×10(-5) mol l(-1) Na-Chl concentration. Comparative analysis of different packaging decontamination treatments indicates that washing with water can diminish pathogen population on the surface by <1log, 100ppm Na-hypochlorite reduces the pathogens about 1·7log and 200ppm Na-hypochlorite by 2·2log. Meanwhile, Na-Chl-based photosensitization reduces bacteria on the surface by 4·2 orders of magnitude. Food-borne pathogen B. cereus could be effectively inactivated (7log) by Na-Chl-based photosensitization in vitro and on the surface of packaging material. Spores are more resistant than vegetative cells to photosensitization-based inactivation. Comparison of different surface decontamination treatments indicates that Na-Chl-based photosensitization is much more effective antibacterial tool than washing with water or 200ppm Na-hypochlorite. Our data support the idea that Na-Chl-based photosensitization has great potential for future application as an environment

Fe N-Heterocyclic Carbene Complexes as Promising Photosensitizers.

PubMed

Liu, Yizhu; Persson, Petter; Sundström, Villy; Wärnmark, Kenneth

2016-08-16

homoleptic bis(tridentate) complexes incorporating (CNHC^Npyridine^CNHC)-type ligands gratifyingly resulted in extension of the (3)MLCT lifetime by more than 2 orders of magnitude compared to the parental [Fe(tpy)2](2+) (tpy = 2,2':6',2″-terpyridine) complex. Quantum chemical (QC) studies also revealed that the (3)MC instead of the (5)MC state likely dictates the deactivation of the (3)MLCT state, a behavior distinct from traditional Fe(II)L6 complexes but rather resembling Ru analogues. A heteroleptic Fe(II) NHC complex featuring mesoionic bis(1,2,3-triazol-5-ylidene) (btz) ligands also delivered a 100-fold elongation of the (3)MLCT lifetime relative to its parental [Fe(bpy)3](2+) (bpy = 2,2'-bipyridine) complex. Again, a Ru-like deactivation mechanism of the (3)MLCT state was indicated by QC studies. With a COOH-functionalized homoleptic complex, a record (3)MLCT lifetime of 37 ps was recently observed on an Al2O3 nanofilm. As a proof of concept, it was further demonstrated that the significant improvement in the (3)MLCT lifetime indeed benefits efficient light harvesting with Fe(II) NHC complexes. For the first time, close-to-unity electron injection from the lowest-energy (3)MLCT state to a TiO2 nanofilm was achieved by a stable Fe(II) complex. This is in complete contrast to conventional Fe(II)L6-derived photosensitizers that could only make use of high-energy photons. These exciting results significantly broaden the understanding of the fundamental photophysics and photochemistry of d(6) Fe(II) complexes. They also open up new possibilities to develop solar energy-converting materials based on this abundant, inexpensive, and intrinsically nontoxic element.

Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin-Polyvinylpyrrolidone-Chitosan Systems.

PubMed

Solovieva, Anna B; Kardumian, Valeria V; Aksenova, Nadezhda A; Belovolova, Lyudmila V; Glushkov, Mikhail V; Bezrukov, Evgeny A; Sukhanov, Roman B; Kotova, Svetlana L; Timashev, Peter S

2018-05-23

By the example of a model process of tryptophan photooxidation in the aqueous medium in the presence of a three-component photosensitizing complex (porphyrin photosensitizer-polyvinylpyrrolidone- chitosan, PPS-PVP-CT) in the temperature range of 20-40 °С, we have demonstrated a possibility of modification of such a process by selecting different molar ratios of the components in the reaction mixture. The actual objective of this selection is the formation of a certain PPS-PVP-CT composition in which PVP macromolecules would coordinate with PPS molecules and at the same time practically block the complex binding of PPS molecules with chitosan macromolecules. Such blocking allows utilization of the bactericidal properties of chitosan to a greater extent, since chitosan is known to depress the PPS photosensitizing activity in PPS-PVP-CT complexes when using those in photodynamic therapy (PDT). The optimal composition of photosensitizing complexes appears to be dependent on the temperature at which the PDT sessions are performed. We have analyzed the correlations of the effective rate constants of tryptophan photooxidation with the photophysical characteristics of the formed complexes.

Intermolecular Structural Change for Thermoswitchable Polymeric Photosensitizer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Wooram; Park, Sin-Jung; Cho, Soojeong

2016-08-17

A switchable photosensitizer (PS), which can be activated at a spe-cific condition beside light, has tremendous advantages for photo-dynamic therapy (PDT). Herein, we developed a thermo-switchable polymeric photosensitizer (T-PPS) by conjugating PS (Pheophor-bide-a, PPb-a) to a temperature-responsive polymer backbone of biocompatible hydroxypropyl cellulose (HPC). Self-quenched PS molecules linked in close proximity by pi-pi stacking in T-PPS were easily transited to an active monomeric state by the tempera-ture induced phase transition of polymer backbones. The tempera-ture responsive inter-molecular interaction changes of PS molecules in T-PPS were demonstrated in synchrotron small-angle X-ray scattering (SAXS) and UV-Vis spectrophotometer analysis. The T-PPS allowed switchablemore » activation and synergistically enhanced cancer cell killing effect at the hyperthermia temperature (45 °C). Our developed T-PPS has the considerable potential not only as a new class of photomedicine in clinics but also as a biosensor based on temperature responsiveness.« less

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

Photosensitivity enhancement of PLZT ceramics by positive ion implantation

DOEpatents

Land, Cecil E.; Peercy, Paul S.

1983-01-01

The photosensitivity of lead lanthanum zirconate titanate (PLZT) ceramic material used in high resolution, high contrast, and non-volatile photoferroelectric image storage and display devices is enhanced significantly by positive ion implantation of the PLZT near its surface. Implanted ions include H.sup.+, He.sup.+, Ne.sup.+, Ar.sup.+, as well as chemically reactive ions from Fe, Cr, and Al. The positive ion implantation advantageously serves to shift the absorption characteristics of the PLZT material from near-UV light to visible light. As a result, photosensitivity enhancement is such that the positive ion implanted PLZT plate is sensitive even to sunlight and conventional room lighting, such as fluorescent and incandescent light sources. The method disclosed includes exposing the PLZT plate to the positive ions at sufficient density, from 1.times.10.sup.12 to 1.times.10.sup.17, and with sufficient energy, from 100 to 500 KeV, to provide photosensitivity enhancement. The PLZT material may have a lanthanum content ranging from 5 to 10%, a lead zirconate content of 62 to 70 mole %, and a lead titanate content of 38 to 30%. The ions are implanted at a depth of 0.1 to 2 microns below the surface of the PLZT plate.

Photosensitized regeneration of carbonyl compounds from oximes.

PubMed

de Lijser, H J Peter; Fardoun, Fadia H; Sawyer, Jody R; Quant, Michelle

2002-07-11

[reaction: see text] Deprotection of oximes to their corresponding carbonyl compounds through the use of photosensitized electron-transfer reactions proceeds in reasonable to good yields. Better yields are obtained in nonpolar solvents and when triplet sensitizers are used. Preliminary mechanistic studies suggest the involvement of an iminoxyl radical.

Frequency domain, time-resolved and spectroscopic investigations of photosensitizers encapsulated in liposomal phantoms

NASA Astrophysics Data System (ADS)

Mermut, Ozzy; Bouchard, Jean-Pierre; Cormier, Jean-Francois; Diamond, Kevin R.; Noiseux, Isabelle; Vernon, Marcia L.; Patterson, Michael S.

2007-07-01

A broadband frequency domain fluorescence lifetime system (from ns to ms time scale) has been developed to study the photochemical and photodynamic behavior of model, well-controlled photosensitizer-encapsulating liposomes. Liposomes are known to be efficient and selective photosensitizer (PS) drug delivery vesicles, however, their chemical and physical effects on the photochemical properties of the photosensitizer have not been well characterized. The liposomes employed in this study (both blank and photosensitizer-complexed) were characterized to determine their: a) size distribution (dynamic light scattering), b) image (scanning electron microscope, confocal fluorescence microscopy), c) concentration of particles (flow cytometry), d) temperature-dependant phase transition behavior (differential scanning calorimetry, and e) spectrofluorescent spectrophotometric properties, e.g. aggregation, in the confined environment. The fluorescence decay behavior of two families of encapsulated photosensitizers, di-and tetrasulfonated metallophthalocyanines, and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH), has been examined as a function of the liposome's physical properties (size-scale, distribution and concentration of scatterer) and the impact of the photosensitizer spatial confinement determined. It is found that the achievable size range and distribution of the PS-liposomes is controlled by the chemical nature of the PS for large liposomes (1000 nm), and is PS independent for small PS-liposomes (~140nm). The lifetime decay behavior was studied for all three photosensitizer-liposome systems and compared before and after confinement. We found the nature of the decay to be similar before and after encapsulation for the sulfonated phthalocyanines containing ionic moieties (primarily monoexponential) but not for HPPH. In the latter, the decay transitioned from multi- to monoexponential decay upon localizing lypophilic HPPH to the liposomal membrane. This behavior

Photosensitized enzyme deactivation and protein oxidation by axial-substituted phosphorus(V) tetraphenylporphyrins.

PubMed

Ouyang, Dongyan; Hirakawa, Kazutaka

2017-10-01

The activity for photodynamic therapy of water-soluble cationic porphyrins, tetraphenylporphyrin P(V) complexes, was investigated. Bis(cyclohexylmethoxy)P(V)tetraphenylporphyrin (DCHMP(V)TPP), dichloroP(V)tetraphenylporphyrin (Cl 2 P(V)TPP), and dimethoxyP(V)tetraphenylporphyrin (DMP(V)TPP) could cause the photosensitized deactivation of tyrosinase. The tryptophan residue of human serum albumin (HSA) and several kinds of amino acids could be damaged by these P(V)porphyrins under visible light irradiation. The photosensitized damage of these biomolecules was inhibited by sodium azide, a singlet oxygen ( 1 O 2 ) quencher, and enhanced in deuterium oxide, suggesting the contribution of 1 O 2 . However, an excess amount of sodium azide did not completely inhibit the photosensitized damage. In addition, the redox potential measurements demonstrated the possibility of electron transfer from tryptophan and tyrosine to photoexcited P(V)porphyrins. These results suggest that electron transfer-mediated oxidation of amino acids contributes to the photosensitized protein and amino acid damage by these P(V)porphyrins. Specifically, Cl 2 P(V)TPP showed the highest photodamaging activity in the P(V)porphyrins used in this study. Oxidized products of amino acids by photoexcited P(V)porphyrins were analyzed with a liquid chromatography-mass spectrometer. Because of the hypoxic condition of a tumor, photodynamic therapy through a 1 O 2 -mediated mechanism should be restricted, and the electron transfer-mediated mechanism may improve the photodynamic effect. In the cases of these P(V)porphyrins, redox potential is the most important factor for photosensitized protein and amino acid oxidation through photoinduced electron transfer. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of polymer matrix on photo-sensitivity of CdSe polymer nanocomposites

NASA Astrophysics Data System (ADS)

Kaur, Ramneek; Tripathi, S. K.

2018-04-01

This paper reports the effect of three different polymer matrices (PVP, PMMA and PVK) and Ag doping on the photo-sensitivity of CdSe polymer nanocomposites. The results reveal that the photoconductivity is high for linear chain polymer nanocomposites as compared to aromatic ones with decreasing trend as: CdSe-PMMA > CdSe-PVP > CdSe-PVK. The large substituents or branches along the polymer backbone hinder the stacking sequences in CdSe-PVK nanocomposites resulting in lowest photoconductivity. On contrary, CdSe-PVK nanocomposite exhibit highest photosensitivity. The reason behind it is the low value of dark conductivity in CdSe-PVK nanocomposite and photoconductive PVK matrix. With Ag doping, no considerable effect on the value of photosensitivity has been observed. The obtained results indicate that the photo-conducting properties of these polymer nanocomposites can be tuned by using different polymer matrices.

Photosensitized cleavage of some olefins as potential linkers to be used in drug delivery

NASA Astrophysics Data System (ADS)

Dinache, Andra; Smarandache, Adriana; Simon, Agota; Nastasa, Viorel; Tozar, Tatiana; Pascu, Alexandru; Enescu, Mironel; Khatyr, Abderrahim; Sima, Felix; Pascu, Mihail-Lucian; Staicu, Angela

2017-09-01

A study of photosensitized cleavage of different olefins as potential linkers for drug carrier complexes is reported. The role of singlet oxygen and the kinetic rates for light induced reactions were estimated by time-resolved measurements of singlet oxygen phosphorescence (at 1270 nm) obtained via 532 nm pulse laser excitation of a photosensitizer. The mixture of each studied olefin with verteporfin (used as photosensitizer) were exposed to low energy visible radiation. The rate constants for singlet oxygen quenching by studied olefins were determined. The irradiated solutions were investigated by FTIR spectroscopy and potential photoproducts were suggested. The experimental results were compared with simulations made by DFT method.

Photosensitive dopants for liquid noble gases

DOEpatents

Anderson, David F.

1988-01-01

In an ionization type detector for high energy radiation wherein the energy of incident radiation is absorbed through the ionization of a liquid noble gas and resulting free charge is collected to form a signal indicative of the energy of the incident radiation, an improvement comprising doping the liquid noble gas with photosensitive molecules to convert scintillation light due to recombination of ions, to additional free charge.

Photosensitive filler minimizes internal stresses in epoxy resins

NASA Technical Reports Server (NTRS)

Dillon, J. N.

1967-01-01

Photosensitive filler is added to curable epoxy resins to minimize stress from internal shrinkage during curing or polymerization. Cinnamic acid resins and cinnamal ketones may be added in the amount of 1 to 3 percent by weight of the resin mixture.

Epileptic spasms and early-onset photosensitive epilepsy in Patau syndrome: An EEG study.

PubMed

Spagnoli, Carlotta; Kugathasan, Umaiyal; Brittain, Helen; Boyd, Stewart G

2015-08-01

Patau syndrome, trisomy 13, is the third commonest autosomal trisomy. It is associated with a 25-50% prevalence of epilepsy, but detailed electroclinical descriptions are rare. The occurrence of early-onset photosensitivity has recently been reported in single patients. We collected electroclinical data on 8 infants (age range from 2 months to 3 years and 9 months, median: 17 months) with Patau syndrome referred for an EEG in our Clinical Neurophysiology Department between 1991 and 2011. All EEGs, case-notes, cytogenetic diagnosis and neuroimaging when available were reviewed; data on the occurrence of seizures, epileptiform discharges, photoparoxysmal response and their characteristics in terms of positive frequencies, latencies, grade and duration were noted and analysed. Two patients had been previously diagnosed with epilepsy (one with tonic spasms and one with multiple seizure types). We found 3 patients with photosensitive myoclonic epilepsy (37.5%), and one with non-photosensitive myoclonic epilepsy. We also recorded non-epileptic myoclonic jerks in one patient known to suffer from epileptic spasms. Among photosensitive patients we found self-limited, Waltz's grade 2-4, spike-wave/polyspike-wave discharges in low, medium and high frequency ranges in two patients and in the high frequency range in the third patient, with latencies and duration from less than 1s to a maximum of 9s. In our cohort of Patau syndrome patients, we found a high prevalence of spasms and photic-induced myoclonic jerks. Photosensitivity shows an unusual early age of onset. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

New Generation of Photosensitizers: Conjugates of Chlorin e 6 With Diamond Nanoparticles

NASA Astrophysics Data System (ADS)

Lapina, V. A.; Bushuk, S. B.; Pavich, T. A.; Vorobey, A. V.

2016-07-01

Conjugates of chlorin e 6 with diamond nanoparticles were synthesized by two methods. The spectral and luminescent properties of the obtained conjugates were studied. It was shown that chlorin e 6 retained its photosensitizing activity in the conjugate. It was established that chlorin e 6 immobilized directly on diamond nanoparticles had higher photosensitizing activity than that conjugated using a spacer. It was observed that chlorin e 6 in the conjugate had higher photolytic stability than the free form.

Singlet Oxygen Detection Using Red Wine Extracts as Photosensitizers.

PubMed

Lagunes, Irene; Vázquez-Ortega, Fernanda; Trigos, Ángel

2017-09-01

Moderate consumption of red wine provides beneficial effects to health. This is attributed to polyphenol compounds present in wine such as resveratrol, quercetin, gallic acid, rutin, and vanillic acid. The amount of these antioxidants is variable; nevertheless, the main beneficial effects of red wine are attributed to resveratrol. However, it has been found that resveratrol and quercetin are able to photosensitize singlet oxygen generation and conversely, gallic acid acts as quencher. Therefore, and since resveratrol and quercetin are some of the most important antioxidants reported in red wines, the aim of this research was to evaluate the photosensitizing ability of 12 red wine extracts through photo-oxidation of ergosterol. The presence of 1 O 2 was detected by ergosterol conversion into peroxide of ergosterol through 1 H NMR analysis. Our results showed that 10 wine extracts were able to act as photosensitizers in the generation of singlet oxygen. The presence of 1 O 2 can damage other compounds of red wine and cause possible organoleptic alterations. Finally, although the reaction conditions employed in this research do not resemble the inherent conditions in wine making processing or storing, or even during its consumption, this knowledge could be useful to prevent possible pro-oxidant effects and avoid detrimental effects in red wines. © 2017 Institute of Food Technologists®.

Synthesis and photodynamic activities of modified corrole derivatives on nasopharyngeal carcinoma cells

NASA Astrophysics Data System (ADS)

Chang, Chi K.; Kong, Pak-Wing; Liu, Hai-Yang; Yeung, Lam-Lung; Koon, Ho-Kee; Mak, Nai-Ki

2006-02-01

Ten trans-A2B and A3-type corrole photosensitizers carrying functional groups were synthesized and screened for PDT activities. Photocytotoxicity was measured by the MTT cell reduction assay on a cultured human nasopharyngeal carcinoma (NPC) cell line (HONE-1). Experimental results indicated that corroles containing a single hydroxyphenyl substituent (3, 4 and 5) exhibit the highest activity among the corrole derivatives investigated. Confocal microscopy revealed that the site of cellular localization of the photosensitizers is predominantly at mitochondria. Also, nuclear staining detected apoptotic cell death.

Cell specific aptamer-photosensitizer conjugates as a molecular tool in photodynamic therapy

PubMed Central

Mallikaratchy, Prabodhika; Tang, Zhiwen

2010-01-01

This paper describes the application of a molecular construct of a photosensitizer and an aptamer for photo-therapeutically targeting tumor cells. The key step in increasing selectivity in chemotherapeutic drugs is to create effective molecular platforms that could target cancer cells but not normal cells. Recently, we have developed a strategy via cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to obtain cell specific aptamers using intact viable cells as targets to select aptamers that can recognize cell membrane proteins with high selectivity and excellent affinity. We have identified an aptamer TD05 that only recognizes Ramos cells, a Burkitt’s lymphoma cell line. Here, the high specificity of aptamers in target cell binding and an efficient phototherapy reagent, Ce6, are molecularly engineered to construct a highly selective Aptamer-photosensitizer conjugates (APS) to effectively destroy target cancer cells. Introduction of the APS conjugates followed by irradiation of light selectively destroyed target Ramos cells but not acute lymphoblastic leukemia and myeloid leukemia cell lines. This study demonstrates that the use of cancer specific aptamers conjugated to a photosensitizer will enhance the selectivity of photodynamic therapy. Coupled with the advantages of the cell-SELEX in generating multiple effective aptamers for diseased cell recognition, we will be able to develop highly efficient photosensitizer based therapeutical reagents for clinical applications. PMID:18058891

The influence of excitation radiation parameters on photosensitized generation of singlet oxygen in water

NASA Astrophysics Data System (ADS)

Il'ina, A. D.; Glazov, A. L.; Semenova, I. V.; Vasyutinskii, O. S.

2016-06-01

Photosensitized generation of singlet oxygen with the aid of Radahlorin® photosensitizer has been investigated. The dependences of the intensity of singlet oxygen phosphorescence and photosensitizer fluorescence on the excitation radiation wavelength in the range of 350-440 nm and on the irradiation dose have been obtained. The dependence of the ratio of the sensitizer fluorescence intensity at about 670 nm to the singlet oxygen phosphorescence intensity at a wavelength of 1270 nm on the excitation radiation wavelength is found to be nonmonotonic and have a minimum near the center of the absorption band on its red wing. The results obtained can be used to monitor the singlet oxygen concentration in solutions.

Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

PubMed

Nair, Lakshmi V; Nazeer, Shaiju S; Jayasree, Ramapurath S; Ajayaghosh, Ayyappanpillai

2015-06-23

Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 μg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC.

Impact of Photosensitizers Activation on Intracellular Trafficking and Viscosity

PubMed Central

Aubertin, Kelly; Bonneau, Stéphanie; Silva, Amanda K. A.; Bacri, Jean-Claude; Gallet, François; Wilhelm, Claire

2013-01-01

The intracellular microenvironment is essential for the efficiency of photo-induced therapies, as short-lived reactive oxygen species generated must diffuse through their intracellular surrounding medium to reach their cellular target. Here, by combining measurements of local cytoplasmic dissipation and active trafficking, we found that photosensitizers activation induced small changes in surrounding viscosity but a massive decrease in diffusion. These effects are the signature of a return to thermodynamic equilibrium of the system after photo-activation and correlated with depolymerization of the microtubule network, as shown in a reconstituted system. These mechanical measurements were performed with two intracellular photosensitizing chlorins having similar quantum yield of singlet oxygen production but different intracellular localizations (cytoplasmic for mTHPC, endosomal for TPCS2a). These two agents demonstrated different intracellular impact. PMID:24386423

Photosensitive TRPs.

PubMed

Hardie, Roger C

2014-01-01

The Drosophila "transient receptor potential" channel is the prototypical TRP channel, belonging to and defining the TRPC subfamily. Together with a second TRPC channel, trp-like (TRPL), TRP mediates the transducer current in the fly's photoreceptors. TRP and TRPL are also implicated in olfaction and Malpighian tubule function. In photoreceptors, TRP and TRPL are localised in the ~30,000 packed microvilli that form the photosensitive "rhabdomere"-a light-guiding rod, housing rhodopsin and the rest of the phototransduction machinery. TRP (but not TRPL) is assembled into multimolecular signalling complexes by a PDZ-domain scaffolding protein (INAD). TRPL (but not TRP) undergoes light-regulated translocation between cell body and rhabdomere. TRP and TRPL are also found in photoreceptor synapses where they may play a role in synaptic transmission. Like other TRPC channels, TRP and TRPL are activated by a G protein-coupled phospholipase C (PLCβ4) cascade. Although still debated, recent evidence indicates the channels can be activated by a combination of PIP2 depletion and protons released by the PLC reaction. PIP2 depletion may act mechanically as membrane area is reduced by cleavage of PIP2's bulky inositol headgroup. TRP, which dominates the light-sensitive current, is Ca(2+) selective (P Ca:P Cs >50:1), whilst TRPL has a modest Ca(2+) permeability (P Ca:P Cs ~5:1). Ca(2+) influx via the channels has profound positive and negative feedback roles, required for the rapid response kinetics, with Ca(2+) rapidly facilitating TRP (but not TRPL) and also inhibiting both channels. In trp mutants, stimulation by light results in rapid depletion of microvillar PIP2 due to lack of Ca(2+) influx required to inhibit PLC. This accounts for the "transient receptor potential" phenotype that gives the family its name and, over a period of days, leads to light-dependent retinal degeneration. Gain-of-function trp mutants with uncontrolled Ca(2+) influx also undergo retinal degeneration

Preclinical studies of vascular acting photosensitizer bacteriopheophorbide for the treatment of prostate cancer

NASA Astrophysics Data System (ADS)

Hetzel, Fred W.; Chen, Qun; Luck, David; Beckers, Jill; Huang, Zheng

2004-06-01

Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the IV infused photosensitizer drug. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week post PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Prostate lesions could be detected by MRI scan as early as 48 h post PDT. Maximum lesion size of 1.5 cm3 and 2.9 cm3 could be achieved at 50 J/cm and 100 J/cm, respectively, with interstitial treatment using a single 1-cm diffuser fiber, suggesting the Tookad-PDT is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat localized prostate cancer.

Synthesis of Tumor-avid Photosensitizer-Gd(III)DTPA conjugates: impact of the number of gadolinium units in T1/T2 relaxivity, intracellular localization, and photosensitizing efficacy.

PubMed

Goswami, Lalit N; White, William H; Spernyak, Joseph A; Ethirajan, Manivannan; Chen, Yihui; Missert, Joseph R; Morgan, Janet; Mazurchuk, Richard; Pandey, Ravindra K

2010-05-19

To develop novel bifunctional agents for tumor imaging (MR) and photodynamic therapy (PDT), certain tumor-avid photosensitizers derived from chlorophyll-a were conjugated with variable number of Gd(III)aminobenzyl DTPA moieties. All the conjugates containing three or six gadolinium units showed significant T(1) and T(2) relaxivities. However, as a bifunctional agent, the 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) containing 3Gd(III) aminophenyl DTPA was most promising with possible applications in tumor-imaging and PDT. Compared to HPPH, the corresponding 3- and 6Gd(III)aminobenzyl DTPA conjugates exhibited similar electronic absorption characteristics with a slightly decreased intensity of the absorption band at 660 nm. However, compared to HPPH, the excitation of the broad "Soret" band (near 400 nm) of the corresponding 3Gd(III)aminobenzyl-DTPA analogues showed a significant decrease in the fluorescence intensity at 667 nm.

Role of photoacoustic effects occurring at laser perforation of skin and laser transcutaneous drug delivery

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Latyshev, Alexei S.

2000-05-01

A further study is given of photoacoustic (PA) drug delivery technologies using an Er:YAG laser, with the main emphasis being placed on the laser perforation of skin and on PA impregnation using an additional covering quartz plate. A mathematical model based on Fick's law for PA impregnation with regard to a free and rigid interface is considered. The histological examination of the perforated guinea-pig skin ex vivo shoed that a powerful PA wave forced skin epidermis to be bent inwards. In biopsies taken 15 min later the nuclei pyknosis of epidermis cells lining the perforated channel was observed. In biopsies obtained 36 hours later an insignificant necrotic lesion remained, whereas 120 hours laser the cells recovered. I twas shown experimentally that the PA signal increased 30 times after applying a quartz plate over the drug solution, which substantially enhanced drug penetration through the skin .The dependancies were obtained of the penetration depth of the haematoporphyrin derivative photosensitizer versus the number of laser pulses and the pressing force applied to the quartz plate. The chromatographic fractionation of Diprospan and Dexamethasone hormonal preparations prior to and after the action of 200 Er:YAG laser-induced PA waves demonstrated that no additional chemical agents resulting from drug dissociation were detected. The application of laser drug delivery methods in respect of treating dermatological diseases is also discussed.

Primary photosensitization in cattle caused by Froelichia humboldtiana.

PubMed

Souza, Paulo E C; Oliveira, Samuel S; Aguiar-Filho, Cristiano R; Cunha, Ana L B; Albuquerque, Raquel F; Evêncio-Neto, Joaquim; Riet-Correa, Franklin; Mendonça, Fábio S

2012-12-01

Three outbreaks of primary photosensitization caused by Froelichia humboldtiana are reported in the semiarid region of the states of Pernambuco and Paraíba, in northeastern Brazil. The disease occurred from March to June 2011, affecting 27 bovines out of a total of 70. The main lesions consisted of dermatitis of the white skin, with edema and necrosis. All the bovines recovered after removal from the areas invaded by F. humboldtiana. To produce the disease experimentally, one bovine with white skin was placed for 14 days into an area with F. humboldtiana as the sole forage. This bovine presented photodermatitis on the third day of consumption. The serum concentrations of total, indirect, and conjugated bilirubin and the serum activities of gamma-glutamyl transferase (GGT) and aspartate-aminotransferase (AST) in the spontaneously affected cattle and in the experimental cattle remained within normal ranges. It is concluded that F. humboldtiana causes primary photosensitization in cattle in northeastern Brazil. Copyright © 2012 Elsevier Ltd. All rights reserved.

Carbon Dots as Versatile Photosensitizers for Solar-Driven Catalysis with Redox Enzymes.

PubMed

Hutton, Georgina A M; Reuillard, Bertrand; Martindale, Benjamin C M; Caputo, Christine A; Lockwood, Colin W J; Butt, Julea N; Reisner, Erwin

2016-12-28

Light-driven enzymatic catalysis is enabled by the productive coupling of a protein to a photosensitizer. Photosensitizers used in such hybrid systems are typically costly, toxic, and/or fragile, with limited chemical versatility. Carbon dots (CDs) are low-cost, nanosized light-harvesters that are attractive photosensitizers for biological systems as they are water-soluble, photostable, nontoxic, and their surface chemistry can be easily modified. We demonstrate here that CDs act as excellent light-absorbers in two semibiological photosynthetic systems utilizing either a fumarate reductase (FccA) for the solar-driven hydrogenation of fumarate to succinate or a hydrogenase (H 2 ase) for reduction of protons to H 2 . The tunable surface chemistry of the CDs was exploited to synthesize positively charged ammonium-terminated CDs (CD-NHMe 2 + ), which were capable of transferring photoexcited electrons directly to the negatively charged enzymes with high efficiency and stability. Enzyme-based turnover numbers of 6000 mol succinate (mol FccA) -1 and 43,000 mol H 2 (mol H 2 ase) -1 were reached after 24 h. Negatively charged carboxylate-terminated CDs (CD-CO 2 - ) displayed little or no activity, and the electrostatic interactions at the CD-enzyme interface were determined to be essential to the high photocatalytic activity observed with CD-NHMe 2 + . The modular surface chemistry of CDs together with their photostability and aqueous solubility make CDs versatile photosensitizers for redox enzymes with great scope for their utilization in photobiocatalysis.

Pentosan-derived water-soluble carbon nano dots with substantial fluorescence: Properties and application as a photosensitizer

NASA Astrophysics Data System (ADS)

Wu, Qiong; Li, Wei; Wu, Yanjiao; Huang, Zhanhua; Liu, Shouxin

2014-10-01

The hydrothermal carbonization of monosaccharides and polysaccharides is widely used in the production of carbonaceous material with a desired structure. However, the liquid products are regarded as waste and discarded. Here, we report a facile approach for the synthesis of water-soluble carbon nano dots (CNDs) with substantial fluorescence from the liquid by-products of the hydrothermal carbonization of pentosan, thus the by-products of pulp refining. The synthesized CNDs are monodispersed spheres with abundant oxygen-containing groups and they have an average size of 30 nm. Quantum yield measurements revealed CNDs with substantial green photoluminescence (PL) without passivation. Additionally, excitation was independent, pH-sensitive and stable. The use of CNDs as a photosensitizer in the CNDs/TiO2 system for methylene blue (MB) degradation under visible light irradiation is attractive. The spectral response range of the CNDs/TiO2 system can be widened from the UV region to a part of the visible light region (400-550 nm).

The effect of UV exposure and heat treatment on crystallization behavior of photosensitive glasses

NASA Astrophysics Data System (ADS)

Kıbrıslı, Orhan; Ersundu, Ali Erçin

2018-05-01

In this study, photosensitive glasses in the Na2O-ZnO-Al2O3-SiO2 system with photosensitizing agents (cerium, silver, tin, antimony) and halogenides (NaF and KBr) were synthesized through a conventional melt-quenching technique. The crystallization mechanism was investigated for solely heat-treated and UV-exposed + heat-treated samples using differential thermal analysis (DTA), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM) techniques to understand the effect of UV exposure on crystallization behavior of photosensitive glasses. Accordingly, non-isothermal DTA measurements were performed at different heating rates to determine crystallization peak, T p, and onset, T c, temperatures. For solely heat-treated samples, the kinetic parameters such as the Avrami constant, n, and morphology index, m, were calculated as 1 from the Ozawa method indicating surface crystallization and the value of crystallization activation energy was calculated as 944 kJ/mol using modified Kissinger method. On the contrary, bulk crystallization was found to be predominant for UV exposed + heat-treated samples revealing that UV exposure is the primary cause of bulk crystallization in photosensitive glasses.

Comparison of high-intensity pulsed and continuous-wave irradiation on benzoporphyrin derivative-induced photosensitization of bladder cancer cells

NASA Astrophysics Data System (ADS)

Diddens, Heyke C.; Gillies, Robert; Hasan, Tayyaba

1994-08-01

Benzoporphyrin derivative, monoacid ring A (BPD-MA) is a second generation porphyrin photosensitizer, with a significant absorption at 692 nm. The ability of two different lasers (a high-intensity pulsed ruby laser, and a continuous wave (cw) argon-ion laser pumped dye laser) in producing photodynamic damage to human bladder carcinoma cells in vitro under similar conditions was compared. Cells incubated in 0.14 (mu) M BPD-MA for 3 hours were irradiated with 1 or 3 J/cm2 with either pulsed or cw irradiation at 694 nm. Cell survival was determined using an MTT assay. With the ruby laser essentially no phototoxicity was observed at the high intensity pulsed irradiances used, whereas 38% and 6% survival rates were observed for 1 and 3 J/cm2, respectively, using cw irradiation. Possible explanations for the lack of BPD-MA phototoxicity using the ruby laser are: rapid photodegradation, saturation and excitation into higher excited states of the sensitizer. No BPD-MA photodegradation was observed in 1.4 (mu) M BPD-MA in 10% fetal calf serum solutions using the ruby laser. However, an oxygen-dependent photodegradation with the formation of a chlorin-type photoproduct was observed in these solutions using cw irradiation. A simple calculation indicated that the high pulse irradiances used in this study (4.4 X 107 W/cm2) were approximately 3 orders of magnitude greater than required for the onset of saturation. If higher excited states (Sn or Tn) are populated, they do not undergo any photochemistry resulting in phototoxicity or in photoproduct formation. These results show that with the low saturation threshold of BPD-MA, the choice of source and irradiance are important considerations in planning a therapeutic regime.

Quenching-induced deactivation of photosensitizer by nanoencapsulation to improve phototherapy of cancer.

PubMed

Zeisser-Labouèbe, Magali; Mattiuzzo, Marc; Lange, Norbert; Gurny, Robert; Delie, Florence

2009-09-01

Photodynamic therapy has emerged as a promising alternative to current cancer treatment. However, conventional photosensitizers have several limitations due to their unsuitable pharmaceutical formulations and lack of selectivity. Our strategy was to exploit the advantages of nanoparticles and the quenching-induced deactivation of the model photosensitizer hypericin to produce "activatable" drug delivery systems. Efficient fluorescence and activity quenching were achieved by increasing the drug-loading rate of nanoparticles. In vitro assays confirmed the reversibility of hypericin deactivation, as the hypericin fluorescence and photodynamic activity were recovered upon cell internalization.

Structural and functional alterations in rhodamine-123- and doxycycline-photosensitized cells

NASA Astrophysics Data System (ADS)

Shea, Christopher R.; Whitaker, Diana; Murphy, George F.; Chen, Norah; Wimberly, Joanne; Scholz, M.; Sherwood, M. E.; Flotte, Thomas J.; Hasan, Tayyaba

1990-06-01

In order to elucidate the mechanisms of photosensitized injury to mitochondria, two photosensitizers have been compared. Both doxycycline (DOTC) and rhodamine-l23 (R123) localize preferentially within the mitochondria of MGH-IJ1 bladder carcinoma cells j1 vitro, and both sensitize phototoxic injury that is selective for mitochondria. Mitochondria of cells pretreated with DOTC and irradiated with UVA (1 J/cm2, 320-400 rim) undergo massive swelling that begins by 10 mm after irradiation, is maximal by 1 h, and is partially repaired by 4 h; damage caused by exposure to a higher UVA dose (6 J/cm2), however, is not repaired. In contrast, cells pretreated with R123 and irradiated with an argon-ion laser (10 J/cm2, 514.5 rim) undergo a different type of mitochondrial injury, characterized by the delayed (4 h) onset of moderate mitochondrial swelling and striking mitochondrial distortion and fragmentation, which is not repaired by 48 h after irradiation. These differences indicate that the reactions underlying cellular phototoxicity can be distinguished even on an ultrastructural level. Probably both the primary photochemistry and the submitochondrial targets of these reactions differ with the two photosensitizers.

Photoacoustic imaging of intravenously injected photosensitizer in rat burn models for efficient antibacterial photodynamic therapy

NASA Astrophysics Data System (ADS)

Tsunoi, Yasuyuki; Sato, Shunichi; Ashida, Hiroshi; Terakawa, Mitsuhiro

2012-02-01

For efficient photodynamic treatment of wound infection, a photosensitizer must be distributed in the whole infected tissue region. To ensure this, depth profiling of a photosensitizer is necessary in vivo. In this study, we applied photoacoustic (PA) imaging to visualize the depth profile of an intravenously injected photosensitizer in rat burn models. In burned tissue, pharmacokinetics is complicated; vascular occlusion takes place in the injured tissue, while vascular permeability increases due to thermal invasion. In this study, we first used Evans Blue (EB) as a test drug to examine the feasibility of photosensitizer dosimetry based on PA imaging. On the basis of the results, an actual photosensitizer, talaporfin sodium was used. An EB solution was intravenously injected into a rat deep dermal burn model. PA imaging was performed on the wound with 532 nm and 610 nm nanosecond light pulses for visualizing vasculatures (blood) and EB, respectively. Two hours after injection, the distribution of EB-originated signal spatially coincided well with that of blood-originated signal measured after injury, indicating that EB molecules leaked out from the blood vessels due to increased permeability. Afterwards, the distribution of EB signal was broadened in the depth direction due to diffusion. At 12 hours after injection, clear EB signals were observed even in the zone of stasis, demonstrating that the leaked EB molecules were delivered to the injured tissue layer. The level and time course of talaporfin sodium-originated signals were different compared with those of EB-originated signals, showing animal-dependent and/or drug-dependent permeabilization and diffusion in the tissue. Thus, photosensitizer dosimetry should be needed before every treatment to achieve desirable outcome of photodynamic treatment, for which PA imaging can be concluded to be valid and useful.

Identification of singlet oxygen photosensitizes in lambs drinking water in an alveld risk area in West Norway.

PubMed

Tønnesen, Hanne Hjorth; Mysterud, Ivar; Karlsen, Jan; Skulberg, Olav M; Laane, Carl M M; Schumacher, Trond

2013-02-05

Alveld is a hepatogenous photosensitivity disorder in lambs. Although alveld has been known in Norway for more than 100years, there are still questions related to the cause of the disease. Phytoporphyrin has long been incriminated as the photosensitizer in hepatogenous photosensitivity diseases but previous findings suggest that the photosensitizing mechanism in alveld is more complex, possibly involving other co-factors. The current work investigates the presence of non-hepatogenous photosensitizers originating in lamb's drinking water from various sources. In addition samples of two of the predominent cyanobacteria found in a representative biofilm (i.e. aggregates of microbes) were identified and isolated in axenic (i.e. pure) cultures. Information from the absorption-, fluorescence emission-, and -excitation spectra and the action spectrum for the formation of singlet oxygen was combined in order to identify the chromophores responsible for the formation of singlet oxygen, e.g. phycocyanins from the cyanobacteria. The highest level of singlet oxygen formation was detected in lotic (i.e. flowing) water in the period consistent with the outbreak of the alveld disease in the area. Meteorological data indicate a warm and wet May with a high radiation exposure leading up to a colder and wet June with an even higher solar irradiance. The seasonal variation in the amount of photosensitizers in lamb's drinking water combined meteorological data can be important to predict the outbreak of alveld. Copyright © 2012 Elsevier B.V. All rights reserved.

Probing Photosensitization by Functionalized Carbon Nanotubes.

PubMed

Chen, Chia-Ying; Zepp, Richard G

2015-12-01

Carbon nanotubes (CNTs) photosensitize the production of reactive oxygen species that may damage organisms by biomembrane oxidation or mediate environmental transformations of CNTs. Photosensitization by derivatized carbon nanotubes from various synthetic methods, and thus with different intrinsic characteristics (e.g., diameter and electronic properties), has been investigated under environmentally relevant aquatic conditions. We used the CNT-sensitized photoisomerization of sorbic acid ((2E,4E)-hexa-2,4-dienoic acid) and singlet oxygen formation to quantify the triplet states ((3)CNT*) formed upon irradiation of selected single-walled carbon nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs). The CNTs used in our studies were derivatized by carboxyl groups to facilitate their dispersion in water. Results indicate that high-defect-density (thus well-stabilized), small-diameter, and semiconducting-rich CNTs have higher-measured excited triplet state formation and therefore singlet oxygen ((1)O2) yield. Derivatized SWCNTs were significantly more photoreactive than derivatized MWCNTs. Moreover, addition of sodium chloride resulted in increased aggregation and small increases in (1)O2 production of CNTs. The most photoreactive CNTs exhibited comparable photoreactivity (in terms of (3)CNT* formation and (1)O2 yield) to reference natural organic matter (NOM) under sunlight irradiation with the same mass-based concentration. Selected reference NOM could therefore be useful in evaluating environmental photoreactivity or intended antibacterial applications of CNTs.

In vivo quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy: influence of photosensitizer formulation and tissue location

NASA Astrophysics Data System (ADS)

de Visscher, Sebastiaan A. H. J.; Witjes, Max J. H.; Kaščáková, Slávka; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.; Roodenburg, Jan L. N.; Amelink, Arjen

2012-06-01

In vivo measurement of photosensitizer concentrations may optimize clinical photodynamic therapy (PDT). Fluorescence differential path-length spectroscopy (FDPS) is a non-invasive optical technique that has been shown to accurately quantify the concentration of Foscan® in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg® and Foslip®, on FDPS response was investigated. Furthermore, FDPS was evaluated in target organs for head-and-neck PDT. Fifty-four healthy rats were intravenously injected with one of the three formulations of mTHPC at 0.15 mg kg-1. FDPS was performed on liver, tongue, and lip. The mTHPC concentrations estimated using FDPS were correlated with the results of the subsequent harvested and chemically extracted organs. An excellent goodness of fit (R2) between FDPS and extraction was found for all formulations in the liver (R2=0.79). A much lower R2 between FDPS and extraction was found in lip (R2=0.46) and tongue (R2=0.10). The lower performance in lip and in particular tongue was mainly attributed to the more layered anatomical structure, which influences scattering properties and photosensitizer distribution.

Gold nanocage-photosensitizer conjugates for dual-modal image-guided enhanced photodynamic therapy.

PubMed

Srivatsan, Avinash; Jenkins, Samir V; Jeon, Mansik; Wu, Zhijin; Kim, Chulhong; Chen, Jingyi; Pandey, Ravindra K

2014-01-01

We have demonstrated that gold nanocage-photosensitizer conjugates can enable dual image-guided delivery of photosensitizer and significantly improve the efficacy of photodynamic therapy in a murine model. The photosensitizer, 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide (HPPH), was noncovalently entrapped in the poly(ethylene glycol) monolayer coated on the surface of gold nanocages. The conjugate is stable in saline solutions, while incubation in protein rich solutions leads to gradual unloading of the HPPH, which can be monitored optically by fluorescence and photoacoustic imaging. The slow nature of the release in turn results in an increase in accumulation of the drug within implanted tumors due to the passive delivery of gold nanocages. Furthermore, the conjugate is found to generate more therapeutic singlet oxygen and have a lower IC50 value than the free drug alone. Thus the conjugate shows significant suppression of tumor growth as compared to the free drug in vivo. Short-term study showed neither toxicity nor phenotypical changes in mice at therapeutic dose of the conjugates or even at 100-fold higher than therapeutic dose of gold nanocages.

In Vitro Antimicrobial Photodynamic Therapy Against Trichophyton mentagrophytes Using New Methylene Blue as the Photosensitizer.

PubMed

López-Chicón, P; Gulías, Ò; Nonell, S; Agut, M

2016-11-01

Antimicrobial photodynamic therapy combines the use of a photosensitizing drug with light and oxygen to eradicate pathogens. Trichophyton mentagrophytes is a dermatophytic fungus able to invade the skin and keratinized tissues. We have investigated the use of new methylene blue as the photosensitizing agent for antimicrobial photodynamic therapy to produce the in vitro inactivation of T mentagrophytes. A full factorial design was employed to optimize the parameters for photoinactivation of the dermatophyte. The parameters studied were new methylene blue concentration, contact time between the photosensitizing agent and the fungus prior to light treatment, and the fluence of red light (wavelength, 620-645nm) applied. The minimum concentration of new methylene blue necessary to induce the death of all T. mentagrophytes cells in the initial suspension (approximate concentration, 10 6 colony forming units per milliliter) was 50μM for a fluence of 81J/cm 2 after a contact time of 10minutes with the photosensitizing-agent. Increasing the concentration to 100μM allowed the fluence to be decreased to 9J/cm 2 . Comparison of our data with other published data shows that the susceptibility of T. mentagrophytes to antimicrobial photodynamic therapy with new methylene blue is strain-dependent. New methylene blue is a photosensitizing agent that should be considered for the treatment of fungal skin infections caused by this dermatophyte. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Systemic reduction of rice blast by means of photosensitizers

USDA-ARS?s Scientific Manuscript database

Acquired disease resistance of plants may be induced by exogenous reactive oxygen species or their sources. Certain compounds (photosensitizers) produce ROS at the expense of light energy. This study used photodynamic dyes bengal rose and methylene blue, which yield singlet oxygen, and mercaptopyrid...

Inhibiting the photosensitized oxidation of anthracene and tryptophan by means of natural antioxidants

NASA Astrophysics Data System (ADS)

Aksenova, N. A.; Vyzhlova, E. N.; Malinovskaya, V. V.; Parfenov, V. V.; Solov'eva, A. B.; Timashev, P. S.

2013-08-01

It is shown that model reactions of photosensitized oxidation of anthracene and tryptophan can be used for evaluation and comparison of antioxidant activity of various classes of compounds. Inhibition of the oxidation of substrates in the presence of the familiar antioxidants tocopherol (vitamin E), ascorbic acid (vitamin C), and mixtures of these vitamins with methionine, and in the presence of reputed antioxidants dihydroquercetin and taurine, are considered. It is concluded that all of the above compounds except for taurine have antioxidant properties; i.e., they reduce the rate constants of the photosensitized oxidation of anthracene and tryptophan. It is found that the inhibition of oxidation is associated with the interaction between antioxidants and singlet oxygen. Analysis of the kinetic dependences of the photosensitized oxidation of substrates in the presence of antioxidants reveals that a mixture of vitamins inhibits the process most efficiently, and inhibition occurs at the initial stages due to more active interaction between singlet oxygen and vitamin C

New Photosensitized Processes at Aerosol and Ocean Surfaces

NASA Astrophysics Data System (ADS)

Rossignol, S.; Aregahegn, K. Z.; Ciuraru, R.; Bernard, F.; Tinel, L.; Fine, L.; George, C.

2014-12-01

From a few years now, there is a growing body of evidence that photoinduced processes could be of great importance for the tropospheric chemistry. Here, we would like to present two additional outcomes of this new area of research, firstly the photosensitized direct VOC uptake by aerosols and, secondly, the photoinduced chemical formation of unsaturated VOC from marine microlayer proxy. It was recently shown that the chemistry of glyoxal toward ammonium ions into droplets and wet aerosols leads to the formation of light-absorbing compounds. Among them, we found that imidazole-2-carboxaldehyde (IC) acts as a photosensitizer and is able to initiate the growth of organic aerosols via the uptake of VOC, such as limonene. Given its potential importance, the mechanism of this photoinduced uptake was investigated thanks to aerosol flow tube experiments and UPLC-ESI-HRMS analysis. Results reveal hydrogen abstraction on the VOC molecule by the triplet state of IC leading to the VOC oxidation without any traditional oxidant. As well as aerosol, the sea-surface microlayer, known to be enriched in light-absorbing organics, is largely impacted by photochemical processes. Recent studies have pointed out for example the role of photosentitized processes in the loss of NO2 and ozone at water surfaces containing photoactive compounds such as chlorophyll. In order to go further, we worked from sea-surface microlayer proxy containing humic acids as photoactive material and organic acids as surfactants. Beside oxidation processes, we monitored by high resolution PTR-MS the release in the gas phase of unsaturated compounds, including C5 dienes (isoprene ?). A strong correlation between the measured surface tension and the C5 diene concentration in the gas phase was evidenced, clearly pointing toward an interfacial process. This contribution will highlight the similarities between both systems and will attempt to present a general chemical scheme for photosensitized chemistry at

The tryptophan-derived endogenous arylhydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ) is a nanomolar UVA-photosensitizer in epidermal keratinocytes

PubMed Central

Williams, Joshua D.; Cabello, Christopher M.; Qiao, Shuxi; Wondrak, Georg T.

2014-01-01

Endogenous UVA-chromophores may act as sensitizers of oxidative stress underlying cutaneous photoaging and photocarcinogenesis, but the molecular identity of non-DNA key chromophores displaying UVA-driven photodyamic activity in human skin remains largely undefined. Here we report that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct and endogenous high affinity aryl hydrocarbon receptor (AhR) agonist, acts as a nanomolar photosensitizer potentiating UVA-induced oxidative stress irrespective of AhR ligand activity. In human HaCaT and primary epidermal keratinocytes, photodynamic induction of apoptosis was elicited by the combined action of solar simulated UVA and FICZ, whereas exposure to the isolated action of UVA or FICZ did not impair viability. In a human epidermal tissue reconstruct, FICZ/UVA-cotreatment caused pronounced phototoxicity inducing keratinocyte cell death, and FICZ photodynamic activity was also substantiated in a murine skin exposure model. Array analysis revealed pronounced potentiation of cellular heat shock, ER stress, and oxidative stress response gene expression observed only upon FICZ/UVA-cotreatment. FICZ photosensitization caused intracellular oxidative stress, and comet analysis revealed introduction of formamidopyrimidine-DNA glycosylase (FPG)-sensitive oxidative DNA lesions suppressible by antioxidant cotreatment. Taken together, our data demonstrate that the endogenous AhR ligand FICZ displays nanomolar photodynamic activity representing a molecular mechanism of UVA-induced photooxidative stress potentially operative in human skin. PMID:25431849

Layer-by-layer hollow photosensitizer microcapsule design via a manganese carbonate hard template for photodynamic therapy in cells.

PubMed

Simioni, Andreza Ribeiro; de Jesus, Priscila Costa Carvalho; Tedesco, Antonio Claudio

2018-06-01

Microcapsules fabricated using layer-by-layer self-assembly have unique properties, making them attractive for drug delivery applications. The technique has been improved, allowing the deposition of multiple layers of oppositely charged polyelectrolytes on spherical, colloidal templates. These templates can be decomposed by coating multiple layers, resulting in hollow shells. In this paper, we describe a novel drug delivery system for loading photosensitizer drugs into hollow multilayered microcapsules for photoprocess applications. Manganese carbonate particles were prepared by mixing NH 4 HCO 3 and MnSO 4 and performing consecutive polyelectrolyte adsorption processes onto these templates using poly-(sodium 4-styrene sulfonate) and poly-(allylamine hydrocholoride). A photosensitizer was also incorporated into the layers. Hollow spheres were fabricated by removing the cores in the acidic solution. The hollow, multilayered microcapsules were studied by scanning electron microscopy, steady-state, and time-resolved techniques. Their biological activity was evaluated in vitro with cancer cells using a conventional MTT assay. The synthesized CaCO 3 microparticles were uniform, non-aggregated, and highly porous spheres. The phthalocyanine derivatives loaded in the microcapsules maintained their photophysical behaviour after encapsulation. The spectroscopic results presented here showed excellent photophysical behaviour of the studied drug. We observed a desirable increase in singlet oxygen production, which is favourable for the PDT protocol. Cell viability after treatment was determined and the proposed microcapsules caused 80% cell death compared to the control. The results demonstrate that photosensitizer adsorption into the CaCO 3 microparticle voids together with the layer-by-layer assembly of biopolymers provide a method for the fabrication of biocompatible microcapsules for use as biomaterials. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-bending of optical waveguides in a dry photosensitive medium

NASA Astrophysics Data System (ADS)

Malallah, Ra'ed; Wan, Min; Muniraj, Inbarasan; Cassidy, Derek; Sheridan, John T.

2018-03-01

Optical waveguide trajectories formed in an AA/PVA a photopolymer material photosensitive at 532 nm are examined. The transmission of light by this materials is discussed. The bending and arching of the waveguides which occur are investigated. The prediction of our model are shown to agree with the observed of trajectories. The largest index changes taking place at any time during the exposure, i.e. during SWW formation are found at the positions where the largest light intensity is present. Typically, such as maxima exist close to the input face at the location of the Primary Eye or at the location of the Secondary Eyes deeper with in the material. All photosensitive materials have a maximum saturation value of refractive index change that it is possible to induce, which is also discussed.

Photosensitized generation of singlet oxygen by rhenium(I) complex

NASA Astrophysics Data System (ADS)

Burchinov, A. N.; Kiselev, V. M.; Penni, A. A.; Khistyaeva, V. V.

2015-12-01

The photosensitized generation of singlet oxygen in solutions of rhenium(I) complex fac-[Re(bipy)(CO)3NCCH3]+OTf-, where bipy=2,2'-bipyridine, in chloride methylene and carbon tetrachloride under continuous LED irradiation in the UV and visible ranges has been investigated.

Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

2005-01-01

In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

In vivo magnetic resonance measures of dark cytotoxicity of photosensitizers in a Murine tumor model

NASA Astrophysics Data System (ADS)

Ramaprasad, Subbaraya; Ripp, Elzbieta; Pi, Jiaxiong; Joshi, Shantaram S.; Pandey, Suresh K.; Missert, Joseph; Pandey, Ravindra K.

2005-04-01

Photodynamic therapy (PDT) is a novel cancer treatment modality where the therapeutic action is controlled by light and the potency of the photosensitizer used. Development of new potent photosensitizers (PS) for clinical applications requires that the PDT effects are maximized while minimizing dark cytotoxicity. The dark toxicity of photosensitizers is generally confirmed using cell lines. Photososensitizers that appear promising from in vitro assays need further investigations under in vivo conditions. As in vivo MR methods have the potential to provide information on the tumor status, they can be very effective tools to study dark toxicity of tumors. The tumor produced on the mouse foot dorsum was tested on two newly synthesized photosensitizers along with Photofrin as a control. The MR studies consisted of serial 31P spectral measurements both before and after PS injection. The results show significant changes in the tumor metabolism with increased inorganic phosphate while using new photosensitizers. However these changes slowly approached control levels several hours later. The studies performed while using Photofrin did not show any significant changes indicating minimal or no dark cytotoxicity. Similar studies performed on normal tissue such as the muscle indicated that the energy metabolism was minimally compromised. Our studies demonstrate that the effects of dark cytotoxicity can be observed by 31P MR. The growth profiles of tumors treated with PS alone indicate that the metabolic changes are temporary and do not interfere with the tumor growth. The studies suggest that MR is a new method of monitoring the effect of PS administered toxicity in an in vivo model.

Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

NASA Astrophysics Data System (ADS)

Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

2009-06-01

Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

Effect of Pluronic F-127 on the photosensitizing activity of tetraphenylporphyrins in organic and aqueous phases

NASA Astrophysics Data System (ADS)

Savko, M. A.; Aksenova, N. A.; Akishina, A. K.; Khasanova, O. V.; Glagolev, N. N.; Rumyantseva, V. D.; Zhdanova, K. A.; Spokoinyi, A. L.; Solov'eva, A. B.

2017-11-01

The solubilization of hydrophobic porphyrin photosensitizers (PPSes) to obtain corresponding water-soluble forms is an important line of modern antimicrobial photodynamic therapy. It is shown that a triblock copolymer of ethylene and propylene oxides, Pluronic F-127, one of the most nontoxic and effective polymer surface active substances (SASes), can be used for the conversion of hydrophobic tetraphenylporphyrin (TPP) and monosubstituted and tetrasubstituted hydroxy, amino, and nitro TPPs into water-soluble forms. It is found that Pluronic has a substantially higher solubilizing affinity (defined as the minimum molar concentration of an SAS required for the complete migration of porphyrin with a specific molar concentration to the aqueous phase) toward monosubstituted TPPs than to corresponding tetrasubstituted porphyrins. It is shown that with Pluronic in the organic phase, the activity of tetraphenylporphyrin in a test reaction of the oxidation of anthracene is higher than that of its monosubstituted and tetrasubstituted derivatives. In an aqueous medium, the activity of solubilized mono derivatives of TPP is comparable to that of unsubstituted TPP and is higher than the activity of the corresponding tetra derivatives of TPP.

Single Cell Responses to Spatially-Controlled Photosensitized Production of Extracellular Singlet Oxygen

PubMed Central

Pedersen, Brian Wett; Sinks, Louise E.; Breitenbach, Thomas; Schack, Nickolass B.; Vinogradov, Sergei A.; Ogilby, Peter R.

2011-01-01

The response of individual HeLa cells to extracellularly produced singlet oxygen was examined. The spatial domain of singlet oxygen production was controlled using the combination of a membrane-impermeable Pd porphyrin-dendrimer, which served as a photosensitizer, and a focused laser, which served to localize the sensitized production of singlet oxygen. Cells in close proximity to the domain of singlet oxygen production showed morphological changes commonly associated with necrotic cell death. The elapsed post-irradiation “waiting period” before necrosis became apparent depended on (a) the distance between the cell membrane and the domain irradiated, (b) the incident laser fluence and, as such, the initial concentration of singlet oxygen produced, and (c) the lifetime of singlet oxygen. The data imply that singlet oxygen plays a key role in this process of light-induced cell death. The approach of using extracellularly-generated singlet oxygen to induce cell death can provide a solution to a problem that often limits mechanistic studies of intracellularly photosensitized cell death: it can be difficult to quantify the effective light dose, and hence singlet oxygen concentration, when using an intracellular photosensitizer. PMID:21668871

X ray photoelectron spectroscopy (XPS) analysis of Photosensitive ZrO2 array

NASA Astrophysics Data System (ADS)

Li, Y.; Zhao, G.; Zhu, R.; Kou, Z.

2018-03-01

Based on organic zirconium source as the starting material, by adding chemical modifiers which are made up with photosensitive ZrO2 sol. A uniformed ZrO2 array dot was fabricated with a mean diameter of around 800 nm. By using UV-vis spectra and X-ray photoelectron spectroscopy analysis method, studies the photosensitive ZrO2 gel film of photochemical reaction process and the photosensitive mechanism, to determine the zirconium atom centered chelate structure, reaction formed by metal chelate Zr atom for the center, and to establish the molecular model of the chelate. And studied the ultraviolet light in the process of the variation of the XPS spectra, Zr3d5/2 to 184.9 eV corresponding to the binding energy of the as the combination of state peak gradually reduce; By combining with the status of Zr-O peak gradually increase; The strength of the peak is gradually decline. This suggests that in the process of ultraviolet light photo chemical reaction happened. This study is of great significance to the micro fabrication of ZrO2 array not only to the memory devices but also to the optical devices.

Strong memory in time series of human magnetoencephalograms can identify photosensitive epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yulmetyev, R. M., E-mail: rmy@theory.kazan-spu.ru; Yulmetyeva, D. G.; Haenggi, P.

2007-04-15

To discuss the salient role of statistical memory effects in human brain functioning, we have analyzed a set of stochastic memory quantifiers that reflects the dynamical characteristics of neuromagnetic responses of magnetoencephalographic signals to a flickering stimulus of different color combinations from a group of control subjects, and compared them with those for a patient with photosensitive epilepsy. We have discovered that the emergence of strong memory and the accompanying transition to a regular and robust regime of chaotic behavior of signals in separate areas for a patient most likely identifies the regions where the protective mechanism against the occurrencemore » of photosensitive epilepsy is located.« less

Organic photosensitive devices using subphthalocyanine compounds

DOEpatents

Rand, Barry [Princeton, NJ; Forrest, Stephen R [Ann Arbor, MI; Mutolo, Kristin L [Hollywood, CA; Mayo, Elizabeth [Alhambra, CA; Thompson, Mark E [Anaheim Hills, CA

2011-07-05

An organic photosensitive optoelectronic device, having a donor-acceptor heterojunction of a donor-like material and an acceptor-like material and methods of making such devices is provided. At least one of the donor-like material and the acceptor-like material includes a subphthalocyanine, a subporphyrin, and/or a subporphyrazine compound; and/or the device optionally has at least one of a blocking layer or a charge transport layer, where the blocking layer and/or the charge transport layer includes a subphthalocyanine, a subporphyrin, and/or a subporphyrazine compound.

Ultrasonic activation and chemical modification of photosensitizers enhances the effects of photodynamic therapy against Enterococcus faecalis root-canal isolates.

PubMed

Tennert, C; Drews, A M; Walther, V; Altenburger, M J; Karygianni, L; Wrbas, K T; Hellwig, E; Al-Ahmad, A

2015-06-01

The aim of this study was to evaluate the effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilms in artificially infected root canals using modified photosensitizers and passive ultrasonic activation. Two hundred and seventy extracted human teeth with one root canal were instrumented utilizing ProTaper files, autoclaved, infected with E. faecalis T9 for 72 h and divided into different groups: irrigation with 3% sodium hypochlorite (NaOCl), 20% ethylenediaminetetraacetic acid (EDTA), or 20% citric acid, PDT without irrigation, PDT accompanied by irrigation with NaOCl, EDTA, or citric acid, PDT using an EDTA-based photosensitizer or a citric-acid-based photosensitizer and PDT with ultrasonic activation of the photosensitizer. A 15 mg/ml toluidine blue served as the photosensitizer, activated by a 100 mW LED light source. Sterile paper points were used for sampling the root canals and dentin chips were collected to assess the remaining contamination after treatment. Samples were cultured on blood agar plates and colony forming units were quantified. PDT alone achieved a reduction in E. faecalis counts by 92.7%, NaOCl irrigation alone and combined with PDT by 99.9%. The antibacterial effects increased by the combination of irrigation using EDTA or citric acid and PDT compared to irrigation alone. More than 99% of E. faecalis were killed using PDT with the modified photosensitizers and ultrasonic activation. NaOCl based disinfection achieved the highest antimicrobial effect. Using PDT with an EDTA-based or citric-acid-based phozosensitizer or activating the photosensitizer with ultrasound resulted in a significantly higher reduction in E. faecalis counts compared to conventional PDT. Copyright © 2015 Elsevier B.V. All rights reserved.

Photobactericidal activity of methylene blue derivatives against vancomycin-resistant Enterococcus spp.

PubMed

Wainwright, M; Phoenix, D A; Gaskell, M; Marshall, B

1999-12-01

The toxicities and phototoxicities of methylene blue and its two methylated derivatives were measured against one standard and three vancomycin-resistant pathogenic strains of Enterococcus spp. Each of the compounds was bactericidal and the derivatives exhibited photobactericidal activity on illumination at a 'light' dose of 6.3 J/cm(2) against one or more of the strains. Increased bactericidal and photobactericidal activity in the methylated derivatives is thought to be due to their higher hydrophobicities allowing greater interaction with the bacterial cell wall. In addition, the derivatives exhibited higher inherent photosensitizing efficacies.

Triple-channel microreactor for biphasic gas-liquid reactions: Photosensitized oxygenations.

PubMed

Maurya, Ram Awatar; Park, Chan Pil; Kim, Dong-Pyo

2011-01-01

A triple-channel microreactor fabricated by means of a soft-lithography technique was devised for efficient biphasic gas-liquid reactions. The excellent performance of the microreactor was demonstrated by carrying out photosensitized oxygenations of α-terpinene, citronellol, and allyl alcohols.

Precise Two-Photon Photodynamic Therapy using an Efficient Photosensitizer with Aggregation-Induced Emission Characteristics.

PubMed

Gu, Bobo; Wu, Wenbo; Xu, Gaixia; Feng, Guangxue; Yin, Feng; Chong, Peter Han Joo; Qu, Junle; Yong, Ken-Tye; Liu, Bin

2017-07-01

Two-photon photodynamic therapy (PDT) is able to offer precise 3D manipulation of treatment volumes, providing a target level that is unattainable with current therapeutic techniques. The advancement of this technique is greatly hampered by the availability of photosensitizers with large two-photon absorption (TPA) cross section, high reactive-oxygen-species (ROS) generation efficiency, and bright two-photon fluorescence. Here, an effective photosensitizer with aggregation-induced emission (AIE) characteristics is synthesized, characterized, and encapsulated into an amphiphilic block copolymer to form organic dots for two-photon PDT applications. The AIE dots possess large TPA cross section, high ROS generation efficiency, and excellent photostability and biocompatibility, which overcomes the limitations of many conventional two-photon photosensitizers. Outstanding therapeutic performance of the AIE dots in two-photon PDT is demonstrated using in vitro cancer cell ablation and in vivo brain-blood-vessel closure as examples. This shows therapy precision up to 5 µm under two-photon excitation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photo-oxidation of ergosterol: indirect detection of antioxidants photosensitizers or quenchers of singlet oxygen.

PubMed

Lagunes, Irene; Trigos, Ángel

2015-04-01

Consumption of antioxidant supplements is associated to prevention of several diseases. However, recent studies suggest that antioxidants, besides scavenge free radicals could lead development of tumors. Due to conflicting reports on the antioxidant benefits, the capacity to photosensitize the generation of singlet oxygen of seven natural antioxidants was evaluated through photo-oxidation of ergosterol which proved to be an efficient method of indirect detection of singlet oxygen. Our results showed that curcumin, resveratrol and quercetin have pro-oxidant activity due they act as photosensitizers in generation of singlet oxygen. In addition, we observed that genistein, naringenin, β-carotene and gallic acid besides their antioxidant activity against ROS radicals, are capable of quenching ROS non-radicals as singlet oxygen. Finally, our results allow us to propose a new approach in classification of natural antioxidants scavengers of free radicals, based on their activity as quenchers of singlet oxygen or as photosensitizers in singlet oxygen generation. Copyright © 2015. Published by Elsevier B.V.

Photoluminescence of cerium fluoride and cerium-doped lanthanum fluoride nanoparticles and investigation of energy transfer to photosensitizer molecules.

PubMed

Cooper, Daniel R; Kudinov, Konstantin; Tyagi, Pooja; Hill, Colin K; Bradforth, Stephen E; Nadeau, Jay L

2014-06-28

CexLa1-xF3 nanoparticles have been proposed for use in nanoscintillator-photosensitizer systems, where excitation of nanoparticles by ionizing radiation would result in energy transfer to photosensitizer molecules, effectively combining the effects of radiotherapy and photodynamic therapy. Thus far, there have been few experimental investigations of such systems. This study reports novel synthesis methods for water-dispersible Ce0.1La0.9F3/LaF3 and CeF3/LaF3 core/shell nanoparticles and an investigation of energy transfer to photosensitizers. Unbound deuteroporphyrin IX 2,4-disulfonic acid was found to substantially quench the luminescence of large (>10 nm diameter) aminocaproic acid-stabilized nanoparticles at reasonable concentrations and loading amounts: up to 80% quenching at 6% w/w photosensitizer loading. Energy transfer was found to occur primarily through a cascade, with excitation of "regular" site Ce(3+) at 252 nm relayed to photosensitizer molecules at the nanoparticle surface through intermediate "perturbed" Ce(3+) sites. Smaller (<5 nm) citrate-stabilized nanoparticles were coated with the bisphosphonate alendronate, allowing covalent conjugation to chlorin e6 and resulting in static quenching of the nanoparticle luminescence: ∼50% at ∼0.44% w/w. These results provide insight into energy transfer mechanisms that may prove valuable for optimizing similar systems.

Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

2003-12-01

Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

Triple-channel microreactor for biphasic gas–liquid reactions: Photosensitized oxygenations

PubMed Central

Maurya, Ram Awatar; Park, Chan Pil

2011-01-01

Summary A triple-channel microreactor fabricated by means of a soft-lithography technique was devised for efficient biphasic gas–liquid reactions. The excellent performance of the microreactor was demonstrated by carrying out photosensitized oxygenations of α-terpinene, citronellol, and allyl alcohols. PMID:21915221

Betacyanins pigments as photosensitizing agents for holographic recording medium

NASA Astrophysics Data System (ADS)

Toxqui-López, S.; Hernández-Hernández, E.; Santacruz-Vázquez, C.; Olivares-Pérez, A.; Santacruz-Vazquez, V.

2014-02-01

One of the natural most employed within the food industry are pigments of betalains by their solubility in water to give desired colorations in processed foods such as beverages, dairy, meat. However, this research shows that this type of pigments can be used as photosensitizing agents in the field of holographic recording materials.

Photodynamic therapy of hamster Greene melanoma in vitro and in vivo using bacteriochlorin-a as photosensitizer

NASA Astrophysics Data System (ADS)

Schuitmaker, J. J.; Van Best, Jaap A.; van Delft, J. L.; Jannink, J. E.; Oosterhuis, J. A.; Vrensen, Gijs F.; Ms Wolff-Rouendaal, Didi; Dubbelman, T. M.

1996-01-01

Efficient photodynamic therapy (PDT) of malignant melanoma may be possible with photosensitizers having absorption maxima in the far-red region e.g., above 700 nm. Bacteriochlorin a (BCA), a non toxic derivative of bacteriochlorphyllin a, has a high molecular absorption coefficient (32.000 M-1.cm-1) at 760 nm. At this wavelength tissue penetration of light is almost optimal and melanin absorption is relatively low. In several series of experiments BCA was proven to be a very effective photosensitizer, in vitro and in vivo. It is preferentially retained in experimental hamster Greene melanoma, rhabdomyosarcoma, RIF- and mamma tumors. Its fluorescence can be detected in vivo, thus enabling early tumor detection and it is rapidly cleared from the tissues which promises no, or minor skin photosensitivity. The effects of BCA-PDT were studied in vitro and in vivo using the heavily pigmented Hamster Greene Melanoma (HGM) cell line as a model. In vitro it was found that the uptake of BCA was time, concentration and temperature dependant. Upon illumination (10 Mw/cm2, 756 nm) after incubation with 2.5 (mu) g/ml BCA for 1 h, almost complete cell kill was obtained within seconds. Hamster Greene Melanoma implanted in the anterior eye chamber of rabbits is an accepted in vivo model for ocular melanoma. The effects of BCA-PDT using this model were studied by light- and electron microscopy. Immediately after PDT intracellular spaces were enlarged and blood vessels were clotted with swollen erythrocytes. Electron microscopy showed fused inner and outer membranes and affected cristae mitchondriales of some mitochondria. With time, the severity of tissue and cell damage increased. One day after irradiation tumor growth had stopped; fluorescein angiography showed non perfusion of the tumor. Histopathology showed almost complete tumor necrosis with occasionally viable cells at the tumor periphery. It is concluded that the direct mitochondrial damage and the vascular damage both

Chlorophyll derivatives for pest and disease control: Are they safe?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azizullah, Azizullah, E-mail: azizswabi@gmail.com; Murad, Waheed

2015-01-15

Chlorophyll derivatives are getting widespread acceptance among the researchers as natural photosensitizers for photodynamic control of pests and disease vectors; however, rare attention has been given to evaluation of their toxicity to non-target organisms in the environment. This perspective article highlights that chlorophyll derivatives may not be as safe as believed and can possibly pose risk to non-target organisms in the environment. We invite the attention of environmental biologists, particularly ecotoxicologists, to contribute their role in making the application of chlorophyll derivatives more environmentally friendly and publicly acceptable.

Ultraviolet photosensitivity of sulfur-doped micro- and nano-crystalline diamond

DOE PAGES

Mendoza, Frank; Makarov, Vladimir; Hidalgo, Arturo; ...

2011-06-06

The room-temperature photosensitivity of sulfur-doped micro- (MCD), submicro- (SMCD) and nano- (NCD) crystalline diamond films synthesized by hot-filament chemical vapor deposition was studied. The structure and composition of these diamond materials were characterized by Raman spectroscopy, scanning electron microscopy and X-ray diffraction. The UV sensitivity and response time were studied for the three types of diamond materials using a steady state broad UV excitation source and two pulsed UV laser radiations. It was found that they have high sensitivity in the UV region, as high as 10 9 sec -1mV -1 range, linear response in a broad spectral range belowmore » 320 nm, photocurrents around ~10 -5 A, and short response time better than 100 ns, which is independent of fluency intensity. A phenomenological model was applied to help understand the role of defects and dopant concentration on the materials’ photosensitivity.« less

Characterization of clinical photosensitivity in cutaneous lupus erythematosus.

PubMed

Foering, Kristen; Chang, Aileen Y; Piette, Evan W; Cucchiara, Andrew; Okawa, Joyce; Werth, Victoria P

2013-08-01

Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. We sought to characterize self-reported PS in cutaneous LE (CLE). The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). PS was inferred from patient report and not directly observed. Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise

Professional photosensitive eczema of fishermen by contact with bryozoans: disabling occupational dermatosis.

PubMed

Clin, Benedicte; Stosse-Guevel, Catherine; Marquignon, Marie-France; Verneuil, Laurence; Letourneux, Marc

2008-01-01

Eczema associated with bryozoans is a form of occupational dermatosis caused by a living animal, involving contact eczema, occasionally associated with photosensitivity and concerning fishermen on a quasi-elective basis. This affection can prove to be extremely disabling, frequently generating disastrous social consequences, since the eviction of the responsible allergen is very often synonymous to occupational reclassification, a measure which fishermen, highly attached to their profession, have great difficulty in accepting. Based on the description of three cases of photosensitive eczema associated with contact with the bryozoan, Alcyonidium gelatinosum, identified in fishermen from the English Channel coastline, we describe the characteristics and the specificities of this occupational dermatosis, then approach the issue of its prevention, which, unfortunately, remains limited.

Incidental retinal phototoxicity associated with ingestion of photosensitizing drugs.

PubMed

Mauget-Faÿsse, M; Quaranta, M; Francoz, N; BenEzra, D; Mauget-Fa, M

2001-07-01

to report on the possible correlation between incident retinal phototoxicity and the use of photosensitizing drugs. four patients were examined because of scotomas and visual loss after an incidental exposure to a strong light source. One patient (two eyes) was exposed to standard camera flash; one patient (one eye) had a brief exposure to welding light; one patient (two eyes) underwent uncomplicated phacoemulsifications with intraocular lens implantation. The fourth patient had a severe retinal phototoxicity following a secondary intraocular lens implantation. All four patients underwent a thorough assessment including history of systemic drug use. These patients had ophthalmologic evaluation including: best corrected visual acuity (ETDRS charts), fundus examination, fluorescein and indocyanine green angiographies and were followed for 1 year. on presentation, the mean visual acuity was 7.5/20 (range: 20/400-20/20). Fundus examination disclosed yellow-gray sub-retinal lesions in all affected eyes. Early phase fluorescein angiography showed one or multiple hypofluorescent spots surrounded by a halo of hyperfluorescent window defect. In the late phase, some of these spots leaked the fluorescein dye. Indocyanine green angiography demonstrated hypofluorescent spots throughout with ill-defined borders of hyperfluorescence observed during the late stages. The common finding in these four patients was the fact that they were all taking one or more photosensitizing drugs (hydrochlorothiazide, furosemide, allopurinol, and benzodiazepines). Three of the patients had a full visual recovery a few months after the phototoxicity. The fourth patient remained with a visual acuity of 20/60 12 months after the light exposure. Despite the visual recovery, non-homogeneous retinal pigment epithelial disturbances persisted in all affected eyes. phototoxicity following incidental light exposure may occur in patients taking drugs of photosensitizing potential. Therefore, the thorough

Photodynamic chlorophyll a metabolites, including phytoporphyrin (phylloerythrin), in the blood of photosensitive livestock: overview and measurement.

PubMed

Campbell, W M; Dombroski, G S; Sharma, I; Partridge, A C; Collett, M G

2010-06-01

To validate a spectrofluorometric method for measuring chlorophyll a metabolites, specifically phytoporphyrin (= phylloerythrin), as well as the chlorins, pheophorbide a and pyropheophorbide a, in the blood of photosensitive cattle and sheep. Standard methanolic solutions of pheophorbide a (25 microM), pyropheophorbide a (25 microM), and phytoporphyrin (<3.7 microM) were prepared. Serum and plasma samples were obtained from cattle (n=5), sheep (n=3), and one alpaca, with clinical facial eczema (i.e. photosensitive), as well as from clinically normal (n=2 of each) adult cows, recently weaned calves, and sheep (controls). Standard solutions of the three metabolites were characterised using high-performance liquid chromatography (HPLC), with mass spectrometry, in conjunction with absorption and emission spectral data, and were compared with sera from photosensitive animals. In the latter, phytoporphyrin was the only metabolite detected. Calibration curves were prepared by adding different ratios of methanol and standard solutions of phytoporphyrin in methanol to diluted serum from control animals. Peak areas of fluorescence spectra were determined in samples from photosensitive animals. Pheophorbide a and pyropheophorbide a produced typical chlorin spectra, and had excitation/emission maxima of 408/669 nm and 409/669 nm, respectively. Phytoporphyrin showed a typical porphyrin fluorescence spectrum, with excitation/ emission maxima of 425/644 nm. Pyropheophorbide a and phytoporphyrin had very similar chromatographic retention times, the same chemical formula and same mass, but were distinguishable by differences in their absorption spectra. In sera from photosensitive animals, the fluorescence emission at 644 nm was shown to arise solely from phytoporphyrin and not from any other chlorophyll a metabolites. Calibration curves using sera and plasma from control animals gave reliable measurements of phytoporphyrin in the range 0.4-6 microM. The sera of facial eczema

Investigation of the oxidation mechanisms of limonene photosensitized by imidazole-2-carboxaldehyde

NASA Astrophysics Data System (ADS)

Rossignol, Stéphanie; Tinel, Liselotte; Aregahegn, Kifle; George, Christian

2013-04-01

Recent studies have revealed the significant formation of light absorbing materials, including imidazole and imidazole derivatives, in aqueous aerosol mimics in the presence of both ammonium sulphate and glyoxal (Galloway et al. 2009; Yu et al. 2011; Kampf et al. 2012). Besides the potential impact on radiative properties of secondary organic aerosols, our team has shown that imidazole-2-carboxaldehyde (IC) acts as a photosensitizer, initiating aerosols growth in the presence of gaseous limonene and UV/visible light (Aregahegn et al., abstract submitted). This work focuses on the characterisation of the chemical mechanisms leading to this aerosols growth, and on the major products identification. The molecular composition of organic/aqueous solutions exposed to UV/visible light and containing IC and limonene is followed in time by HR-ESI-MS/MS in positive and negative modes. Limonene consumption is followed by HPLC-UV. HR-ESI-MS/MS analyses are performed in parallel on IC/ammonium sulphate aerosols exposed to gaseous limonene and UV/visible light, in particular to assess the relevance of in solution experiments. Besides, the lifetime of the triplet state of IC in aqueous/organic solutions in the presence of different terpenes is monitored by laser photolysis experiments and compared in order to explain the first steps of the photosensitized reaction. First HR-ESI-MS/MS results show the formation of the major "traditional" limonene oxidation products (e.g., coming from gas phase limonene ozonolysis) during the irradiation of organic solutions containing IC and limonene: limononaldehyde, keto-limononaldehyde, limonic acid, limononic acid ... Hundreds of other oxygenated species are however detected, typically with a number of carbon atoms ranging from 4 to 20 and with O/C ratios ranging from 0.2 to 0.7. Monomers and dimers of limonene oxidation products are observed but species with lower carbon numbers than monomeric compounds are predominant. Moreover, and

Preparation, characterization, and cellular studies of photosensitizer-loaded lipid nanoparticles for photodynamic therapy

NASA Astrophysics Data System (ADS)

Navarro, Fabrice P.; Bechet, Denise; Delmas, Thomas; Couleaud, Pierre; Frochot, Céline; Verhille, Marc; Kamarulzaman, Ezatul; Vanderesse, Régis; Boisseau, Patrick; Texier, Isabelle; Gravier, Julien; Vinet, Françoise; Barberi-Heyob, Muriel; Couffin, Anne Claude

2011-02-01

PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for different kinds of cancer. Among various attempts to enhance the therapeutics efficacy of PDT, the specific delivery of the PhotoSensitizer (PS) in the tumor is expected to increase its clinical applications, since unwanted accumulation, especially in the skin, impairs the patients' quality of life (prolonged cutaneous photosensitivity). The aim of this study was to engineer Lipid Nanoparticles (LNP) with different sizes and various PS contents, using simple, solvent-free and easily scale up manufacturing processes. Meso-tetra (hydroxyphenyl) chlorin (mTHPC) is one of the most potent photoactive compounds for clinical use and it has been successfully applied in the treatment of various indications, such as the head and neck, prostate and pancreatic cancers. Here, a derivative of mTHPC was efficiently incorporated into the lipid core of LNP, leading to a large range of stable and reproducible mTHPC-loaded LNP with narrow size distribution. The photophysical and photochemical properties of mTHPC-loaded LNP were studied by measuring absorbance and fluorescence spectra, colloidal stability, particle size and zeta potential, as well as singlet oxygen luminescence. The photocytotoxicity of three selected mTHPC-loaded LNP (25 nm, 45 nm and 95 nm of diameter, respectively) was evaluated on MCF-7 cells, in comparison to free mTHPC, under irradiation at 652 nm with a range of light fluence from 1 to 5 J/cm2. All the physico-chemical, photophysical and biological measurements allow us to conclude that LNP is a promising nano-drug delivery system for PDT.

Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers

NASA Astrophysics Data System (ADS)

Brozek-Pluska, B.; Kopec, M.

2016-12-01

Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed.

Methyl pyropheophorbide-a analogues: potential fluorescent probes for the peripheral-type benzodiazepine receptor. Effect of central metal in photosensitizing efficacy.

PubMed

Chen, Yihui; Zheng, Xiang; Dobhal, Mahabeer P; Gryshuk, Amy; Morgan, Janet; Dougherty, Thomas J; Oseroff, Allan; Pandey, Ravindra K

2005-06-02

Pyropheophorbides and their metal complexes were synthesized to investigate their applications as nonradioactive peripheral benzodiazepine receptor (PBR) binding probes and photosensitizers for use in photodynamic therapy. They were found to be localized in mitochondria and showed significant binding to PBR. In some cases, the PBR binding values were similar to that for 17 (PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide). However, no direct correlation between 17 displacement ability and photosensitizing efficacy of photosensitizers was observed.

Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivative for bacterial skin infection

NASA Astrophysics Data System (ADS)

Chen, Zhuo; Zhang, Yaxin; Li, Linsen; Zhou, Shanyong; Chen, Jincan; Hu, Ping; Huang, Mingdong

2014-09-01

Folliculitis, furunculosis and acne vulgaris are very common skin disorders of the hair follicles and are associated with large grease-producing (sebaceous) glands. Although the detailed mechanisms involved these skin disorders are not fully understood, it is believed that the bacteria Propionibacterium acnes and Staphylococcus aureus are the key pathogenic factors involved. Conventional treatments targeting the pathogenic factors include a variety of topical and oral medications such as antibiotics. The wide use of antibiotics leads to bacterial resistance, and hence there is a need for new alternatives in above bacterial skin treatment. Photodynamic antimicrobial chemotherapy (PACT) is based on an initial photosensitization of the infected area, followed by irradiation with visible light, producing singlet oxygen which is cytotoxic to bacteria. Herein we reported a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5) and its PACT effect for the bacteria involved in these skin infections. Our results demonstrated strong bactericidal effects of this photosensitizer on both strains of the bacteria, suggesting ZnPc-(Lys)5 as a promising antimicrobial photosensitizer for the treatment of infectious diseases caused by these bacteria.

The nature and molecular basis of cutaneous photosensitivity reactions to psoralens and coal tar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pathak, M.A.; Joshi, P.C.

1983-06-01

The basic aspects of cutaneous photosensitization reactions and the mode of therapeutic effectiveness of psoralens and coal tar, the two groups of photosensitizing agents used extensively in the photochemotherapy of psoriasis, have been reviewed. Psoralen-induced skin photosensitization and the therapeutic action of psoralens involve two distinct types of reactions, and these two reactions occur independently of each other and concurrently when the psoralen-treated skin (oral or topical) is exposed to 320 to 400 nm of radiation. The first, type I, is an oxygen-independent reaction and primarily involves photoreaction with DNA; the second, type II, is a sensitized reaction dependent onmore » oxygen and involves the formation of singlet oxygen (1O2). The photoreactive form of psoralen is its triplet state, and the sites of reaction are (1) the cell membrane of the epidermal, dermal, and endothelial cells; (2) the cytoplasmic constituents, such as enzymes, RNA, lysosomes, etc.; (3) the cell nuclei (DNA and chromatin); and (4) the sensitized production of 1O2, which is responsible for cell-membrane damage and vasodilation. The major damage would be initiated by a type I reaction and would be seen in the form of nuclear damage to DNA resulting from the interaction of psoralen with DNA and to a lesser extent with RNA. The skin photosensitization response (erythema, edema, membrane damage, etc.) would result from a type II reaction involving the generation of 1O2. Crude coal tar (CCT), widely used in the Goeckerman therapy for psoriasis, also produces type I and type II reactions. The therapeutic and photosensitizing actions of CCT are due to (1) the photoconjugation of the photoreactive ingredients of CCT with DNA, causing interstrand cross-links; and (2) the production of 1O2. CCT is an efficient producer of 1O2, more so than 8-methoxypsoralen, and is responsible for cell-membrane damage and cellular edema.« less

Tooth color change caused by photosensitizers after photodynamic therapy: An in vitro study.

PubMed

Costa, Larissa Menezes; Matos, Felipe de Souza; Correia, Ayla Macyelle de Oliveira; Carvalho, Nayane Chagas; Faria-E-Silva, André Luís; Paranhos, Luiz Renato; Ribeiro, Maria Amália Gonzaga

2016-07-01

This study aimed to perform an in vitro evaluation of the effect of photosensitizers used in photodynamic therapy (PDT) on tooth color change when used in combination with conventional endodontic treatment. Forty extracted human mandibular premolars were accessed and underwent root canal therapy and PDT. Photosensitizers were used in accordance with the experimental groups: MB (n=10) - PDT with Methylene Blue at 0.01%; TB (n=10) - PDT with Toluidine Blue at 0.01%; MG (n=10) - PDT with Malachite Green at 0.01%, at the concentration of 0.1mg/mL; and PC (n=10) - positive control, PDT with Endo-PTC cream stained with Methylene Blue at 25%. The samples were irradiated with 660-nm diode laser by means of a 330-μm-diameter optical fiber cable at a power density of 40mW for 120s. After light curing, the photosensitizers were removed from the specimens with 10mL sodium hypochlorite at 1%. A reflectance spectrometer was used for evaluation of color prior to and 60days after the experimental procedure based on the CIE L*a*b* system. According to ANOVA test, there were statistically significant differences between the experimental groups (p=0.003). Tukey's test showed a significant difference between PC and TB (p=0.008), as well as between MG and TB (p=0.009). However, there was no statistically significant difference between PC, MG (p=0.957) and MB (p=0.103). It was concluded that the use of PDT as an adjuvant to root canal therapy, using different photosensitizers, led to color change in tooth structure. Copyright © 2016 Elsevier B.V. All rights reserved.

Photosensitized singlet oxygen generation and detection: Recent advances and future perspectives in cancer photodynamic therapy.

PubMed

Li, Buhong; Lin, Lisheng; Lin, Huiyun; Wilson, Brian C

2016-12-01

Photodynamic therapy (PDT) uses photosensitizers and visible light in combination with molecular oxygen to produce reactive oxygen species (ROS) that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature and stimulate the host immune system. The excited singlet state of oxygen ( 1 O 2 ) is recognized to be the main cytotoxic ROS generated during PDT for the majority of photosensitizers used clinically and for many investigational new agents, so that maximizing its production within tumor cells and tissues can improve the therapeutic response, and several emerging and novel approaches for this are summarized. Quantitative techniques for 1 O 2 production measurement during photosensitization are also of immense importance of value for both preclinical research and future clinical practice. In this review, emerging strategies for enhanced photosensitized 1 O 2 generation are introduced, while recent advances in direct detection and imaging of 1 O 2 luminescence are summarized. In addition, the correlation between cumulative 1 O 2 luminescence and PDT efficiency will be highlighted. Meanwhile, the validation of 1 O 2 luminescence dosimetry for PDT application is also considered. This review concludes with a discussion on future demands of 1 O 2 luminescence detection for PDT dosimetry, with particular emphasis on clinical translation. Eye-catching color image for graphical abstract. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photosensitized degradation of losartan potassium in an extemporaneous suspension formulation.

PubMed

Seburg, Randal A; Ballard, John M; Hwang, Tsang-Lin; Sullivan, Caitlin M

2006-10-11

During development of an extemporaneous suspension formulation for losartan potassium, previously unknown degradation products were observed in experimental suspensions prepared in a commercial cherry syrup vehicle. These degradates increased rapidly when analytical solutions prepared from that suspension were exposed to ambient light. The structures of the degradates were determined using a combination of preparative HPLC, LC/MS, (13)C and (1)H NMR (1D and 2D), and mechanistic chemistry. Each degradate results from destruction of the imidazole ring of losartan. Formation of the two major degradates required exposure to light (UV or visible) and the presence of oxygen. Experiments using Rose Bengal (a singlet oxygen photosensitizer) and 1,4-diazabicyclooctane (DABCO; a singlet oxygen quencher) established that the major photodegradates are formed via the intermediacy of singlet oxygen. The identity of the photosensitizer in the formulation was not unequivocally determined; however, the experiments implicated the artificial flavoring in fulfilling this role.

Use of chloro-aluminum sulfonated phthalocyanine as a photosensitizer in the treatment of malignant tumors in dogs and cats

NASA Astrophysics Data System (ADS)

Peavy, George M.; Klein, Mary K.; Newman, H. C.; Roberts, Walter G.; Berns, Michael W.

1991-05-01

Chloro-aluminum sulfonated phthalocyanine (CASPc) has been proposed as a photosensitizing agent for photodynamic therapy (PDT) of neoplasia. This paper reviews the results of PDT treatment using CASPc as a photosensitizing agent in the treatment of 15 cats representing 23 sites of facial, solar induced squamous cell carcinoma, 4 dogs with hemangiopericytomas, 3 dogs with fibrosarcomas, and 1 dog with multiple cutaneous mast cell tumors. The results of this study to date suggest that CASPc is a good photosensitizing agent for the treatment of some forms of spontaneously occurring malignant neoplasia and should be more thoroughly evaluated for this purpose.

Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers.

PubMed

Brozek-Pluska, B; Kopec, M

2016-12-05

Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel type 1 photosensitizers: viability of leukemia cells exposed to reactive intermediates generated in situ by in vitro photofragmentation

NASA Astrophysics Data System (ADS)

Rajagopalan, Raghavan; Karwa, Amol; Lusiak, Przemyslaw M.; Srivastava, Kripa; Poreddy, Amruta R.; Pandurangi, Raghootama S.; Galen, Karen P.; Neumann, William L.; Cantrell, Gary E.; Dorshow, Richard B.

2009-06-01

Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), sulfenato (-S-O-) and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation were prepared and tested for cell viability using U397 leukemia cell line. The azido photosensitizer was conjugated to leukemia cell binding peptide, SFFWRLS, for targeted cell viability study. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light. Most importantly, selective cell death was observed with the azido peptide conjugate 6, which clearly demonstrates that these Type 1 sensitizers are useful for phototherapeutic applications.

Quantum Yield of Cyclobutane Pyrimidine Dimer Formation Via the Triplet Channel Determined by Photosensitization.

PubMed

Liu, Lizhe; Pilles, Bert M; Gontcharov, Julia; Bucher, Dominik B; Zinth, Wolfgang

2016-01-21

UV-induced formation of the cyclobutane pyrimidine dimer (CPD) lesion is investigated by stationary and time-resolved photosensitization experiments. The photosensitizer 2'-methoxyacetophenone with high intersystem crossing efficiency and large absorption cross-section in the UV-A range was used. A diffusion controlled reaction model is presented. Time-resolved experiments confirmed the validity of the reaction model and provided information on the dynamics of the triplet sensitization process. With a series of concentration dependent stationary illumination experiments, we determined the quantum efficiency for CPD formation from the triplet state of the thymine dinucleotide TpT to be 4 ± 0.2%.

Synthesis and biological evaluation of 173-dicarboxylethyl-pyropheophorbide-a amide derivatives for photodynamic therapy.

PubMed

Zhu, Wei; Wang, Lai-Xing; Chen, Dan-Ye; Gao, Ying-Hua; Yan, Yi-Jia; Wu, Xiao-Feng; Wang, Mi; Han, Yi-Ping; Chen, Zhi-Long

2017-12-19

Three novel 17 3 -dicarboxylethyl-pyropheophorbide-a amide derivatives as photosensitizers for photodynamic therapy (PDT) were synthesized from pyropheophorbide-a (Ppa). Their photophysical and photochemical properties, intracellular localization, photocytotoxicity in vitro and in vivo were investigated. All target compounds exhibited low cytotoxicity in the dark and remarkable photocytotoxicity against human esophageal cancer cells. Among them, 1a showed highest singlet oxygen quantum yield. Upon light activation, 1a exhibited significant photocytotoxicity. After PDT treatment, the growth of Eca-109 tumor in nude mice was significantly inhibited. Therefore, 1a is a powerful and promising antitumor photosensitizer for PDT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Visible-Light-Induced Nickel-Catalyzed Negishi Cross-Couplings by Exogenous-Photosensitizer-Free Photocatalysis.

PubMed

Abdiaj, Irini; Fontana, Alberto; Gomez, M Victoria; de la Hoz, Antonio; Alcázar, Jesús

2018-03-22

The merging of photoredox and transition-metal catalysis has become one of the most attractive approaches for carbon-carbon bond formation. Such reactions require the use of two organo-transition-metal species, one of which acts as a photosensitizer and the other one as a cross-coupling catalyst. We report herein an exogenous-photosensitizer-free photocatalytic process for the formation of carbon-carbon bonds by direct acceleration of the well-known nickel-catalyzed Negishi cross-coupling that is based on the use of two naturally abundant metals. This finding will open new avenues in cross-coupling chemistry that involve the direct visible-light absorption of organometallic catalytic complexes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Endogenous and exogenous porphyrins as photosensitizers in the Hep-2 human carcinoma cell line.

PubMed

Alvarez, M G; Milanesio, M; Rivarola, V; Durantini, E; Batlle, A; Fukuda, H

2009-07-01

The photodynamic activity of three photosensitizers (PS): AL-induced PPIX, the porphyrin derivative 5-(4-trimethylammoniumphenyl)-10, 5, 20-tris (2,4,6- trimethoxyphenyl) porphyrin (CP) and the molecular dyad porphyrin-C(60) (P-C(60)), the last two incorporated into liposomal vesicles, was evaluated on Hep-2 human larynx carcinoma cell line. ALA-induced accumulation of the endogenous PS PPIX, reached saturation values between 5 and 24 h incubation time; the maximal PPIX content was 5.7 nmol/106 cells. The same intracellular level was accumulated when the cationic porphyrin CP was used, while the amount of P-C(60) attained was 1.5 nmol/106 cells. Under violet-blue exciting light, the fluorescence of PPIX and P-C(60) was found in the cytoplasm showing a granular appearance indicating lysosomal localization. CP was mainly detected as a filamentous pattern characteristic of mitochondrial localization. No dark cytotoxicity was observed using 1mM ALA, 5 microM CP and 1 microM P-C(60) after 24 h incubation. Cell morphology was analyzed using Hoechst-33258, toluidine blue staining, TUNEL assay and DNA fragmentation, 24 h after irradiation with 54 J/cm2. When photosensitized with ALA and P-C(60), chromatine condensation characteristic of apoptotic cell death was found; instead, 58 % of necrotic cells were observed with CP. The results show that in the Hep-2 cells, of the three PS analyzed, the molecular dyad P-C(60) was more efficient than CP and PPIX, and confirm that PDT can induce different mechanisms of cell death depending on the PS and the irradiation dose.

Spectral characteristics and photosensitization of TiO2 nanoparticles in reverse micelles by perylenes.

PubMed

Hernández, Laura I; Godin, Robert; Bergkamp, Jesse J; Llansola Portolés, Manuel J; Sherman, Benjamin D; Tomlin, John; Kodis, Gerdenis; Méndez-Hernández, Dalvin D; Bertolotti, Sonia; Chesta, Carlos A; Mariño-Ochoa, Ernesto; Moore, Ana L; Moore, Thomas A; Cosa, Gonzalo; Palacios, Rodrigo E

2013-04-25

We report on the photosensitization of titanium dioxide nanoparticles (TiO2 NPs) synthesized inside AOT (bis(2-ethylhexyl) sulfosuccinate sodium salt) reverse micelles following photoexcitation of perylene derivatives with dicarboxylate anchoring groups. The dyes, 1,7-dibromoperylene-3,4,9,10-tetracarboxy dianhydride (1), 1,7-dipyrrolidinylperylene-3,4,9,10-tetracarboxy dianhydride (2), and 1,7-bis(4-tert-butylphenyloxy)perylene-3,4,9,10-tetracarboxy dianhydride (3), have considerably different driving forces for photoinduced electron injection into the TiO2 conduction band, as estimated by electrochemical measurements and quantum mechanical calculations. Fluorescence anisotropy measurements indicate that dyes 1 and 2 are preferentially solubilized in the micellar structure, creating a relatively large local concentration that favors the attachment of the dye to the TiO2 surface. The binding process was followed by monitoring the hypsochromic shift of the dye absorption spectra over time for 1 and 2. Photoinduced electron transfer from the singlet excited state of 1 and 2 to the TiO2 conduction band (CB) is indicated by emission quenching of the TiO2-bound form of the dyes and confirmed by transient absorption measurements of the radical cation of the dyes and free carriers (injected electrons) in the TiO2 semiconductor. Steady state and transient spectroscopy indicate that dye 3 does not bind to the TiO2 NPs and does not photosensitize the semiconductor. This observation was rationalized as a consequence of the bulky t-butylphenyloxy groups which create a strong steric impediment for deep access of the dye within the micelle structure to reach the semiconductor oxide surface.

Effectiveness of partially soluble photosensitizer in photodynamic microbiological inactivation: a curcumin example

NASA Astrophysics Data System (ADS)

Pratavieira, Sebastião.; Matroodi, Fatima; Pinto-Júnior, Fabio Francisco; Rastelli, Alessandra Nara Souza; Bagnato, Vanderlei S.; Guimarães, Francisco E. G.

2017-07-01

We show that partial solubility of a photosensitizer is not necessarily a bad property when dealing with microbiological control. The presence of curcumin aggregates in solution may present advantages with respect the photoand chemical stability.

Brain activation during intermittent photic stimulation: a [15O]-water PET study on photosensitive epilepsy.

PubMed

da Silva, E A; Müller, R A; Chugani, D C; Shah, J; Shah, A; Watson, C; Chugani, H T

1999-01-01

Intermittent photic stimulation (IPS) is an activation procedure used during electroencephalogram (EEG) recording to elicit paroxysmal discharges in individuals with photosensitivity. Specific responses on EEG recording may be provoked by IPS at different frequencies of flickering in normal individuals and in patients with photosensitive epilepsy. Changes in regional cerebral blood flow (rCBF) were studied during IPS in two groups of subjects by using [15O]-water positron emission tomography (PET): a control group consisting of eight healthy adults with photic driving response during IPS on EEG recording (mean age, 25 +/- 10.5 years) without history of neurologic or psychiatric abnormalities and a patient group consisting of four adults (mean age, 33 +/- 7.5 years) with history of photosensitive epilepsy. [15O]-water PET scanning with concomitant EEG monitoring was performed during baseline and IPS at 4-, 14-, and 30-Hz frequencies. The control group showed photic driving response at 14-Hz IPS frequency. The patient group showed photoparoxysmal response at 14 and 30 Hz, but not at 4 Hz. Changes in rCBF were determined by means of statistical parametric mapping. Increases in rCBF in occipital cortex (Brodmann's areas 17, 18, and 19) were observed in both groups. In addition, during photic driving responses, the control group showed rCBF increases in the insula and in the thalamus, on the right side. The patient group showed a significant rCBF increase in the hypothalamic region inferior to the left caudate nucleus during photoparoxysmal response. This activation was not found in the control group. Increased rCBF also was observed in the patient group in the head of the left caudate nucleus, in the left hippocampus, and in left insula during IPS without photoparoxysmal response. No activations in these regions were observed during photoparoxysmal response. These data may indicate involvement of the hypothalamus in photosensitive epilepsy and may suggest a modulatory

Pyropheophorbide-a methyl ester-mediated photosensitization activates transcription factor NF-kappaB through the interleukin-1 receptor-dependent signaling pathway.

PubMed

Matroule, J Y; Bonizzi, G; Morlière, P; Paillous, N; Santus, R; Bours, V; Piette, J

1999-01-29

Pyropheophorbide-a methyl ester (PPME) is a second generation of photosensitizers used in photodynamic therapy. We demonstrated that PPME photosensitization activated NF-kappaB transcription factor in colon cancer cells. Unexpectedly, this activation occurred in two separate waves, i.e. a rapid and transient one and a second slower but sustained phase. The former was due to photosensitization by PPME localized in the cytoplasmic membrane which triggered interleukin-1 receptor internalization and the transduction pathways controlled by the interleukin-1 type I receptor. Indeed, TRAF6 dominant negative mutant abolished NF-kappaB activation by PPME photosensitization, and TRAF2 dominant negative mutant was without any effect, and overexpression of IkappaB kinases increased gene transcription controlled by NF-kappaB. Oxidative stress was not likely involved in the activation. On the other hand, the slower and sustained wave could be the product of the release of ceramide through activation of the acidic sphingomyelinase. PPME localization within the lysosomal membrane could explain why ceramide acted as second messenger in NF-kappaB activation by PPME photosensitization. These data will allow a better understanding of the molecular basis of tumor eradication by photodynamic therapy, in particular the importance of the host cell response in the treatment.

Novel method for in vitro depletion of T cells by monoclonal antibody-targeted photosensitization.

PubMed

Berki, T; Németh, P

1998-02-01

An immunotargeting method (called photo-immunotargeting) has been developed for selective in vitro cell destruction. The procedure combines the photosensitizing (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the selective binding ability of monoclonal antibodies (mAb) to cell surface molecules. The photosensitizer HP molecules were covalently attached to monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T lymphocytes, and used for T cell destruction. To increase the selectivity of the conventional targeting methods, a physical activation step (local light irradiation) as a second degree of specificity was employed. The HP in conjugated form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after irradiation at 400 nm, at tenfold lower concentration compared to the photosensitizing effect of unbound HP. The selective killing of T lymphocytes (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a treatment with the phototoxic conjugate and light irradiation. This method can be useful for selective destruction of one population (target cell) in an in vitro heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion to avoid graft vs. host reaction.

Electrospun photosensitive nanofibers: potential for photocurrent therapy in skin regeneration.

PubMed

Jin, Guorui; Prabhakaran, Molamma P; Kai, Dan; Kotaki, Masaya; Ramakrishna, Seeram

2013-01-01

Poly(3-hexylthiophene) (P3HT) is one of the most promising photovoltaic (PV) polymers in photocurrent therapy. A novel photosensitive scaffold for skin tissue engineering was fabricated by blending P3HT with polycaprolactone (PCL) and electrospun to obtain composite PCL/P3HT nanofibers with three different weight ratios of PCL : P3HT (w/w) of 150 : 2 [PCL/P3HT(2)], 150 : 10 [PCL/P3HT(10)] and 150 : 20 [PCL/P3HT(20)]. The photosensitive properties of the blend solutions and the composite nanofibers of PCL/P3HT were investigated. The incident photon-to-electron conversion efficiencies of the PCL/P3HT(2), PCL/P3HT(10), PCL/P3HT(20) were identified as 2.0 × 10(-6), 1.6 × 10(-5) and 2.9 × 10(-5), respectively, which confirm the photosensitive ability of the P3HT-containing scaffolds. The biocompatibility of the scaffold was evaluated by culturing human dermal fibroblasts and the results showed that the proliferation of HDFs under light stimulation on PCL/P3HT(10) was 12.8%, 11.9%, and 11.6% (p ≤ 0.05) higher than the cell growth on PCL, PCL/P3HT(2) and PCL/P3HT(20), respectively. Human dermal fibroblasts cultured under light stimulation on PCL/P3HT(10) not only showed better cell proliferation but also retained cell morphology similar to the phenotype observed on tissue culture plates (control). Our experimental results suggest novel and potential application of an optimized amount of P3HT-containing scaffold, especially PCL/P3HT(10) nanofibrous scaffold in photocurrent therapy for skin regeneration.

Prospective study of luminous radiation associated technology photosensitive compounds for treatment of diseases

NASA Astrophysics Data System (ADS)

Pires-Santos, Gustavo M.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Sampaio, Fernando José P.; Brugnera, Aldo; Zanin, Fátima Antônia A.; Almeida, Paulo; Pinheiro, Antônio L. B.

2015-03-01

Prospective studies are based on the analysis of patent documents and aims to assess the both technological history and development providing innovation opportunities. This study was a technological prospection mapping aiming to identify breakthrough in PDT and the new possibilities of the technology. Therefore, research in the bank patent 'Spacenet Patent Search' was performed using determinants descriptors associated with the theme: 'A61K41', 'A61N5 / 06'. Were analyzed in this study 326 documents. In evaluating these patents, it was possible to observe an increase in the number of deposits over time, with peak between 1990 and 2000. The highest number of inventors of this area are part of the private sector and the US appear as main producer of technology. It was also observed that blue light, porphyrins and their derivatives are the main topics. It may be concluded that PDT still offers a large opportunity for growth as several wavelengths, and photosensitizers that may be used in the technique.

A theoretical study of a series of water-soluble triphenylamine photosensitizers for two-photon photodynamic therapy.

PubMed

Wang, Xin; Yin, Xue; Lai, Xiao-Yong; Liu, Ying-Tao

2018-10-05

In this study, the therapeutic activity of a series of water-soluble triphenylamine (TP) photosensitizers (Ps) was explored by using theoretical simulations. The key photophysical parameters which determined the efficiency of Ps, such as absorption electronic spectra, singlet-triplet energy gaps and spin-orbit matrix elements were calculated at density functional theory and its time-dependent extension (DFT, TD-DFT). The calculated results showed that these TP photosensitizers possessed large two-photon absorption cross-section in the near-infrared region (NIR), efficient intersystem crossing (ISC) transition from the first singlet excited state to the low lying triplet excited states and sufficient energy for generating reactive oxygen species (ROS). These suitable features made these TP series holding great promise for applications in two-photon photodynamic therapy (PDT). These TP photosensitizers studied here in principle extended the application range of two-photon PDT in water solution. Copyright © 2018 Elsevier B.V. All rights reserved.

Primary photosensitization caused by ingestion of Froelichia humboldtiana by dairy goats.

PubMed

Santos, Danielle S; Silva, Caio C B; Araújo, Valber O; de Fátima Souza, Maria; Lacerda-Lucena, Patrícia B; Simões, Sara V D; Riet-Correa, Franklin; Lucena, Ricardo B

2017-01-01

This study aimed to describe the first report of an outbreak of primary photosensitization in dairy goats caused by Froelichia humboldtiana. The disease occurred from March to May 2014, in a mixed flock of 15 Saanen, Alpine, and crossbred lactating goats. The entire flock was affected; however, the Saanen and cross-bred goats developed more severe lesions, and their milk production decreased by as much as 75%. Lesions were progressive and consisted of skin hyperemia, edema, and necrosis, especially in depigmented areas. An experimental study with two goats resulted in photodermatitis, similar to that observed in the natural cases, 10-14 days after the beginning of plant ingestion. Serum activities of aspartate aminotransferase (AST) and -glutamyltransferase (GGT) and, direct, indirect, and total bilirubin serum concentrations were within the normal ranges. In conclusion, F. humboldtiana causes primary photosensitization in goats with a negative impact on milk production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional PET Evaluation of the Photosensitive Baboon

PubMed Central

Szabó, C. Ákos; Salinas, Felipe S; Narayana, Shalini

2011-01-01

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes. PMID:22276085

Study of Photosensitive Dry Films Absorption for Printed Circuit Boards by Photoacoustic Technique

NASA Astrophysics Data System (ADS)

Hernández, R.; Zaragoza, J. A. Barrientos; Jiménez-Pérez, J. L.; Orea, A. Cruz; Correa-Pacheco, Z. N.

2017-08-01

In this work, the study of photosensitive dry-type films by photoacoustic technique is proposed. The dry film photoresist is resistant to chemical etching for printed circuit boards such as ferric chloride, sodium persulfate or ammonium, hydrochloric acid. It is capable of faithfully reproducing circuit pattern exposed to ultraviolet light (UV) through a negative. Once recorded, the uncured portion is removed with alkaline solution. It is possible to obtain good results in surface mount circuits with tracks of 5 mm. Furthermore, the solid resin films are formed by three layers, two protective layers and a UV-sensitive optical absorption layer in the range of 325 nm to 405 nm. By means of optical absorption of UV-visible rays emitted by a low-power Xe lamp, the films transform this energy into thermal waves generated by the absorption of optical radiation and subsequently no-radiative de-excitation occurs. The photoacoustic spectroscopy is a useful technique to measure the transmittance and absorption directly. In this study, the optical absorption spectra of the three layers of photosensitive dry-type films were obtained as a function of the wavelength, in order to have a knowledge of the absorber layer and the protective layers. These analyses will give us the physical properties of the photosensitive film, which are very important in curing the dry film for applications in printed circuit boards.

Exogenous indirect photoinactivation of bacterial pathogens and indicators in water with natural and synthetic photosensitizers in simulated sunlight with reduced UVB.

PubMed

Maraccini, P A; Wenk, J; Boehm, A B

2016-08-01

To investigate the UVB-independent and exogenous indirect photoinactivation of eight human health-relevant bacterial species in the presence of photosensitizers. Eight bacterial species were exposed to simulated sunlight with greatly reduced UVB light intensity in the presence of three synthetic photosensitizers and two natural photosensitizers. Inactivation curves were fit with shoulder log-linear or first-order kinetic models, from which the presence of a shoulder and magnitude of inactivation rate constants were compared. Eighty-four percent reduction in the UVB light intensity roughly matched a 72-95% reduction in the overall bacterial photoinactivation rate constants in sensitizer-free water. With the UVB light mostly reduced, the exogenous indirect mechanism contribution was evident for most bacteria and photosensitizers tested, although most prominently with the Gram-positive bacteria. Results confirm the importance of UVB light in bacterial photoinactivation and, with the reduction of the UVB light intensity, that the Gram-positive bacteria are more vulnerable to the exogenous indirect mechanism than Gram-negative bacteria. UVB is the most important range of the sunlight spectrum for bacterial photoinactivation. In aquatic environments where photosensitizers are present and there is high UVB light attenuation, UVA and visible wavelengths can contribute to exogenous indirect photoinactivation. © 2016 The Society for Applied Microbiology.

Light-driven photosensitizer uptake increases Candida albicans photodynamic inactivation.

PubMed

Romano, Renan A; Pratavieira, Sebastião; Silva, Ana P da; Kurachi, Cristina; Guimarães, Francisco E G

2017-11-01

Photodynamic Inactivation (PDI) is based on the use of a photosensitizer (PS) and light that results mainly in the production of reactive oxygen species, aiming to produce microorganism cell death. PS incubation time and light dose are key protocol parameters that influence PDI response; the correct choice of them can increase the efficiency of inactivation. The results of this study show that a minor change in the PDI protocol, namely light-driven incubation leads to a higher photosensitizer and more uniform cell uptake inside the irradiated zone. Furthermore, as the uptake increases, the damage caused by PDI also increases. The proposed light-driven incubation prior to the inactivation illumination dose has advantages when compared to the traditional PDI treatments since it can be more selective and effective. Using a violet light as pre-illumination (light-driven incubation) source and a red-light system as PDI source, it was possible to demonstrate that when compared to the traditional protocol of dark incubation, the pre-illuminated cell culture showed an inactivation increase of 7 log units. These in vitro results performed in Candida albicans cells may result in the introduction of a new protocol for PDI. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discontinuous/continuous metal films grown on photosensitive glass

NASA Astrophysics Data System (ADS)

Trotter, D. M., Jr.; Smith, D. W.

1984-07-01

A new effect which allows direct formation of thin metal films of controlled morphology is described. Patterns of glass-ceramic opal are developed in photosensitive glass samples by UV irradiation and heat treatment. The samples are then ion exchanged in molten salt baths containing Ag+ or Cu+ ions. On subsequent firing in a hydrogen atmosphere, continuous films with typical thin metal films properties grow on the opal regions of the samples. Discontinuous films, characterized by activated resistivities and switching, grow on the glassy regions.

Antimicrobial photodynamic therapy with two photosensitizers on two oral streptococci: an in vitro study

NASA Astrophysics Data System (ADS)

Vahabi, S.; Fekrazad, R.; Ayremlou, S.; Taheri, S.; Lizarelli, R. F. Z.; Kalhori, K. A. M.

2011-12-01

Periodontal diseases are caused by infection of tissues supporting the teeth due to complex aggregate of bacteria known as biofilm and firstly colonized by streptococci. The aim of this in vitro study was to evaluate the effect of Radachlorin® and Toluidine Blue O (TBO)-mediated photodynamic therapy (PDT) on the viability of two oral streptococci. Bacterial suspensions of Streptococcus mutans and Streptococcus sanguis were subjected to either TBO or Radachlorin®, Then exposed to two different diode laser light at energy densities of 3, 6 J/cm2 at 633 nm and 6, 12 J/cm2 at 662 nm, respectively. The control groups were subjected to laser light alone, photosensitizer alone or received neither photosensitizer nor light exposure. The suspensions were then spread over specific agar mediums and viable microorganisms were counted after overnight incubation aerobically at 37°C, 5% CO2 and then reported as colony forming unit. The results indicated that photosensitization by the energy density of 6 J/cm2 with Radachlorin® and both 3 and 6 J/cm2 with TBO caused significant reduction in bacterial colony formation ( p < 0.05). Radachlorin® and TBO-mediated photodynamic therapy seem to show excellent potential in significantly killing of two oral streptococci in vitro.

Spectrometric characteristics and tumor-affinity of a novel photosensitizer: mono-l-aspartyl aurochlorin e6 (Au-NPe6).

PubMed

Ishizumi, Taichiro; Aizawa, Katsuo; Tsuchida, Takaaki; Okunaka, Tetsuya; Kato, Harubumi

2004-12-01

Photodiagnosis and photodynamic therapy with photosensitizers can be indicated only for tumors of the superficial type, because these approaches utilizing visible light are limited by said light penetrability. To overcome this disadvantage, we innovated a novel photosensitizer, mono-l-aspartyl aurochlorin e6 (Au-NPe6), by incorporating a gold atom in the center of tetrapyrrole ring of NPe6 with a coordination bond. The gold atom in Au-NPe6 plays a role as an X-ray interceptor to detect deeply sited tumors. In this study, the absorption spectrum of novel Au-NPe6 in the diagnosis of deeply sited tumors was investigated, and the results were compared with the parent photosensitizer NPe6. Furthermore, the tumor-affinity of Au-NPe6 was evaluated using atomic absorption spectrometry. Despite the fact that both photosensitizers display a difference in the absorption spectrum, waveform changes of either photosensitizer with human serum albumin established a saturation point at a molar ratio of 1:1. The results indicate that it is highly possible that Au-NPe6 bound with albumin at a molar ratio (1:1) similar to NPe6. The accumulation rate of gold in tumor tissues was always significantly (p<0.05) higher than that in normal muscle tissues during the observation terms. Moreover, absorption spectra of tumor-tissue homogenates obtained from tumor-bearing mice after Au-NPe6 administration revealed a common peak with a wavelength equivalent to that of albumin-bond Au-NPe. This result suggests that the gold atom and NPe6 probably remained bonded even when Au-NPe6 was incorporated in tumor tissues.

Lipid composition affects the rate of photosensitized dissipation of cross-membrane diffusion potential on liposomes

PubMed Central

Ytzhak, Shany; Wuskell, Joseph P.; Loew, Leslie M.; Ehrenberg, Benjamin

2010-01-01

Hydrophobic or amphiphilic tetrapyrrole sensitizers are taken up by cells and are usually located in cellular lipid membranes. Singlet oxygen is photogenerated by the sensitizer and it diffuses in the membrane and causes oxidative damage to membrane components. This damage can occur to membrane lipids and to membrane-localized proteins. Depolarization of the Nernst electric potential on cells’ membranes has been observed in cellular photosensitization, but it was not established whether lipid oxidation is a relevant factor leading to abolishing the resting potential of cells’ membranes and to their death. In this work we studied the effect of liposomes’ lipid composition on the kinetics of hematoporphyrin-photosensitized dissipation of K+-diffusion electric potential that was generated across the membranes. We employed an electrochromic voltage-sensitive spectroscopic probe that possesses a high fluorescence signal response to the potential. We found a correlation between the structure and unsaturation of lipids and the leakage of the membrane, following photosensitization. As the extent of non-conjugated unsaturation of the lipids is increased from 1 to 6 double bonds, the kinetics of depolarization become faster. We also found that the kinetics of depolarization is affected by the percentage of the unsaturated lipids in the liposome: as the fraction of the unsaturated lipids increases the leakage trough the membrane is enhanced. When liposomes are composed of a lipid mixture similar to that of natural membranes and photosensitization is being carried out under usual photodynamic therapy (PDT) conditions, photodamage to the lipids is not likely to cause enhanced permeability of ions through the membrane, which would have been a mechanism that leads to cell death. PMID:20536150

Effect of soybean lecithin on iron-catalyzed or chlorophyll-photosensitized oxidation of canola oil emulsion.

PubMed

Choe, Jeesu; Oh, Boyoung; Choe, Eunok

2014-11-01

The effect of soybean lecithin addition on the iron-catalyzed or chlorophyll-photosensitized oxidation of emulsions consisting of purified canola oil and water (1:1, w/w) was studied based on headspace oxygen consumption using gas chromatography and hydroperoxide production using the ferric thiocyanate method. Addition levels of iron sulfate, chlorophyll, and soybean lecithin were 5, 4, and 350 mg/kg, respectively. Phospholipids (PLs) during oxidation of the emulsions were monitored by high performance liquid chromatography. Addition of soybean lecithin to the emulsions significantly reduced and decelerated iron-catalyzed oil oxidation by lowering headspace oxygen consumption and hydroperoxide production. However, soybean lecithin had no significant antioxidant effect on chlorophyll-photosensitized oxidation of the emulsions. PLs in soybean lecithin added to the emulsions were degraded during both oxidation processes, although there was little change in PL composition. Among PLs in soybean lecithin, phosphatidylethanolamine and phosphatidylinositol were degraded the fastest in the iron-catalyzed and the chlorophyll-photosensitized oxidation, respectively. The results suggest that addition of soybean lecithin as an emulsifier can also improve the oxidative stability of oil in an emulsion. © 2014 Institute of Food Technologists®

[Participation of oxygen in the reduction of methylviologen, photosensitized by chlorophyll, in an aqueous solution of detergent].

PubMed

Luganskaia, A N; Krasnovskiĭ, A A

1975-01-01

Dependence of chlorophyll "a" photosensitized reduction of methylviologene with tiourea on the temperature of reaction mixture was studied in aerobic conditions in triton X-100 aqueous solution. It was found that the reaction consisted of two stages: the light and dark ones. Photosensitized oxidation of tiourea with air oxygen proceeds at the temperatures up to -70 degrees C. Reduction of methylviologen is a dark stage for which diffusion processes are necessary. The role of hydrogen peroxide in the reaction studied has been investigated. It has been shown that hydrogen peroxide is not the "initiator" of the reaction which results in the reduction of methylviologen. Reduced glutation and the mixture of reduced and oxidized glutations were used as electron donors in photosensitized reaction in the presence of air oxygen. An increase of the depth and rate of the reduction of methylviologen under aerobic conditions as compared to anaerobic ones points to the formation of more active reducers than the initial electron donor.

Photosensitive graphene transistors.

PubMed

Li, Jinhua; Niu, Liyong; Zheng, Zijian; Yan, Feng

2014-08-20

High performance photodetectors play important roles in the development of innovative technologies in many fields, including medicine, display and imaging, military, optical communication, environment monitoring, security check, scientific research and industrial processing control. Graphene, the most fascinating two-dimensional material, has demonstrated promising applications in various types of photodetectors from terahertz to ultraviolet, due to its ultrahigh carrier mobility and light absorption in broad wavelength range. Graphene field effect transistors are recognized as a type of excellent transducers for photodetection thanks to the inherent amplification function of the transistors, the feasibility of miniaturization and the unique properties of graphene. In this review, we will introduce the applications of graphene transistors as photodetectors in different wavelength ranges including terahertz, infrared, visible, and ultraviolet, focusing on the device design, physics and photosensitive performance. Since the device properties are closely related to the quality of graphene, the devices based on graphene prepared with different methods will be addressed separately with a view to demonstrating more clearly their advantages and shortcomings in practical applications. It is expected that highly sensitive photodetectors based on graphene transistors will find important applications in many emerging areas especially flexible, wearable, printable or transparent electronics and high frequency communications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The NPe6 fluorescence measurements by using a fluorescence sensing system for skin photosensitivity risk assessment after photodynamic therapy

NASA Astrophysics Data System (ADS)

Ohtani, Keishi; Usuda, Jitsu; Ogawa, Emiyu; Maehara, Sachio; Imai, Kentaro; Inoue, Tatsuya; Hagiwara, Masaru; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Arai, Tsunenori; Ikeda, Norihiko

2018-02-01

Background: Skin photosensitivity is a major side effect of photodynamic therapy (PDT). It is induced by the photosensitizer remaining in the skin. It is usually rapidly metabolized by the liver, but the pharmacokinetic profile varies widely among individuals. This makes it difficult to predict the incidence of skin photosensitivity. Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after NPe6-PDT could be measured safely in human patients using a fluorescence sensing system for judging the risk of skin photosensitivity. Methods: The NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10 minutes after NPe6 administration as well as at the time of PDT (4-5 hours after administration), at discharge (2 or 3 days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT. Results: Nine male patients and one female patient entered this study. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2-3 days after administration) in most cases and it decreased at 1 or 2 weeks after PDT. Conclusions: The fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring fluorescence intensity in the skin might be useful to predict the incidence of skin photosensitivity after PDT.

Highly enhanced ultraviolet photosensitivity and recovery speed in electrospun Ni-doped SnO2 nanobelts

NASA Astrophysics Data System (ADS)

Huang, Siya; Matsubara, Kohei; Cheng, Jing; Li, Heping; Pan, Wei

2013-09-01

Precisely controlled Ni-doped SnO2 (NSO) nanobelt arrays are synthesized and assembled via electrospinning. In comparison to pristine SnO2 nanobelts, enhanced photosensitivity (˜103) as well as recovery speed (˜1 s) is obtained in NSO nanobelts. The mechanism is clarified by the compensation effect of acceptor impurity Ni, which not only promotes the oxygen-surface interaction but also introduces trapping centers in SnO2 matrix. The reduced grain size (˜4 nm) along with increased depletion layer thickness also benefits the photosensitivity of NSO nanobelts. These improved photoresponse properties make the NSO nanobelt a promising candidate for high-performance ultraviolet detectors.

Photosensitizer quantitation in vivo by flourescence microsampling

NASA Astrophysics Data System (ADS)

Pogue, Brian W.; Burke, Gregory C.; Lee, Claudia C.; Hoopes, P. Jack

2000-06-01

Photodynamic therapy can provide a reliable method of tumor destruction when the appropriate dosimetry is applied. Current dosimetry practice involves quantification of the drug and light doses applied to the tumor, but it would be desirable to monitor in vivo light and drug levels to provide the most accurate determination of dosimetry. In vivo measurements can be used to minimize variations in treatment response due to inter-animal variability, by providing animal-specific or patient-specific treatment planning. This study reports on the development of a micro-sampling method to measure fluorescence from tissue, which is not significantly affected by the tissue optical properties. The system measures fluorescence from the surface of a tissue, using a fiber bundle composed of individual 100 micron fibers which ar all spaced apart by 700 microns from one another at the tissue contact end. This design provides sampling of the fluorescence at multiple sites to increase the signal intensity, while maintaining a micro- sampling of the tissue volume just below the surface. The calibration studies here indicate that the 1/e sampling depth is near 60 microns when measured in optical phantoms, which are similar to typical tissue properties. The probe fluorescence signal is independent of blood concentration up to a maximum of 10% blood by volume, which is similar to most tumor tissue. Animal tests indicate that the sensitivity to drug concentration is essentially the same in when measured in murine liver and muscle tissues, both in vivo and ex vivo. These preliminary calibration results suggest that the probe can be used to measure photosensitizer uptake in vivo non- invasively and rapidly via conversion of fluorescence intensity to photosensitizer concentration.

Isoproturon Reappearance after Photosensitized Degradation in the Presence of Triplet Ketones or Fulvic Acids.

PubMed

Yuan, Chenyi; Chakraborty, Mrinal; Canonica, Silvio; Weavers, Linda K; Hadad, Christopher M; Chin, Yu-Ping

2016-11-15

Isoproturon (IPU) is a phenylurea herbicide used to control broad-leaf grasses on grain fields. Photosensitized transformation induced by excited triplet states of dissolved organic matter ( 3 DOM*) has been identified as an important degradation pathway for IPU in sunlit waters, but the reappearance of IPU in the absence of light is observed after the initial photolysis. In this study, we elucidate the kinetics of this photodegradation and dark-reappearance cycling of IPU in the presence of DOM proxies (aromatic ketones and reference fulvic acids). Using mass spectrometry and nuclear magnetic resonance spectroscopic techniques, a semi-stable intermediate (IPU int ) was found to be responsible for IPU reversion and was identified as a hydroperoxyl derivative of IPU. IPU int is photogenerated from incorporation of diatomic oxygen to IPU and is subjected to thermolysis whose rate depends on temperature, pH, the presence of DOM, and inorganic ions. These results are important to understand the overall aquatic fate of IPU and structurally similar compounds under diurnal conditions.

New photosensitive systems for volume phase holography

NASA Astrophysics Data System (ADS)

Bianco, Andrea; Colella, Letizia; Galli, Paola; Zanutta, Alessio; Bertarelli, Chiara

2017-05-01

Volume phase holographic elements are becoming attractive thanks to the large efficiency and good optical quality. They are based on photosensitive materials where a modulation of the refractive index is induced. In this paper, we highlight the strategies to obtain a change in the refractive index in a dielectric material, namely a change in the material density and/or in the molecular polarizability. Moreover, we show the results achieved for materials that undergo the photo-Fries reaction as function of the molecular structure and the illumination conditions. We also report the results on a system based on the diazo Meldrum's acid where volatile molecules are produced upon light exposure.

Luminescence of Radachlorin Photosensitizer in Aqueous Solution under Excitation at 405 and 660 nm

NASA Astrophysics Data System (ADS)

Beltukova, D. M.; Belik, V. P.; Vasyutinskii, O. S.; Gadzhiev, I. M.; Goncharov, S. E.; Semenova, I. V.

2018-01-01

Entire luminescence spectrum of a commercial photosensitizer Radachlorin in aqueous solution has been recorded under laser excitation at 660 nm and analyzed. The peak of singlet oxygen phosphorescence at 1274 nm has been observed. The results obtained were compared with those recorded with laser excitation at 405 nm and reported earlier. The comparison showed the similarity of relaxation and luminescence processes occurring in both cases. Effective absorption cross sections were determined at each excitation wavelength, it was also shown that the singlet oxygen quantum yield is independent of photosensitizer concentration. The lifetime of the first excited triplet state in Radachlorin was determined. The results obtained can be used for optimization of the conditions of singlet oxygen generation and detection in solutions and biological samples.

Reactive oxygen species explicit dosimetry (ROSED) of a type 1 photosensitizer

NASA Astrophysics Data System (ADS)

Ong, Yi Hong; Kim, Michele M.; Huang, Zheng; Zhu, Timothy C.

2018-02-01

Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy.

PubMed

Li, Wenjing; Tan, Sihai; Xing, Yutong; Liu, Qian; Li, Shuang; Chen, Qingle; Yu, Min; Wang, Fengwei; Hong, Zhangyong

2018-04-02

Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts its clinical applications. A higher accumulation of photosensitizers is very important for the treatment of deeply seated and larger tumors. The conjugation of Pyro with tumor-homing peptide ligands could be a very useful strategy to optimize the physical properties of Pyro. Herein, we reported our studies on the conjugation of Pyro with a cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, to develop highly tumor-specific photosensitizers for PDT application. To further reduce the nonspecific uptake and, thus, reduce the background distribution of the conjugates in normal tissues, we opted to add a highly hydrophilic polyethylene glycol (PEG) chain and an extra strongly hydrophilic carboxylic acid group as the linker to avoid the direct connection of the strongly hydrophobic Pyro macrocycle and cRGD ligand. We reported here the synthesis and characterization of these conjugates, and the influence of the hydrophilic modification on the biological function of the conjugates was carefully studied. The tumor-accumulation ability and photodynamic-induced cell-killing ability of these conjugates were evaluated through both in vitro cell-based experiment and in vivo distribution and tumor therapy experiments with tumor-bearing mice. Thus, the synthesized conjugate significantly improved the tumor enrichment and tumor selectivity of Pyro, as well as abolished the xenograft tumors in the murine model through a one-time PDT treatment.

Photosensitivity enhancement of PLZT ceramics by positive ion implantation

DOEpatents

Peercy, P.S.; Land, C.E.

1980-06-13

The photosensitivity of lead lanthanum zirconate titanate (PLZT) ceramic material used in high resolution, high contrast, and non-volatile photoferroelectric image storage and display devices is enhanced significantly by positive ion implantation of the PLZT near its surface. Ions that are implanted include H/sup +/, He/sup +/, Ar/sup +/, and a preferred co-implant of Ar/sup +/ and Ne/sup +/. The positive ion implantation advantageously serves to shift the band gap energy threshold of the PLZT material from near-uv light to visible blue light. As a result, photosensitivity enhancement is such that the positive ion implanted PLZT plate is sensitive even to sunlight and conventional room lighting, such as fluorescent and incandescent light sources. The method disclosed includes exposing the PLZT plate to these positive ions of sufficient density and with sufficient energy to provide an image. The PLZT material may have a lanthanum content ranging from 5 to 10%; a lead zirconate content ranging from 62 to 70 mole %; and a lead titanate content ranging from 38 to 30%. The region of ion implantation is in a range from 0.1 to 2 microns below the surface of the PLZT plate. Density of ions is in the range from 1 x 10/sup 12/ to 1 x 10/sup 17/ ions/cm/sup 2/ and having an energy in the range from 100 to 500 keV.

Synthesis of a chitosan-based photo-sensitive hydrogel and its biocompatibility and biodegradability.

PubMed

He, Ming; Han, Baoqin; Jiang, Zhiwen; Yang, Yan; Peng, Yanfei; Liu, Wanshun

2017-06-15

Hydroxyethyl chitosan (HECTS) is one of the most important water soluble derivatives of chitosan. In this study, photo-sensitive azidehydroxyethyl chitosan (AZ-HECTS) was synthesized with grafting degree 3.4%, and its water solution resulted in an insoluble hydrogel by 254nm UV irradiation for 90s. AZ-HECTS hydrogels, with water absorption 86.21%, had little impact on growth of mouse fibroblast (L929) and presented good cell biocompatibility. Obvious sudden degradation stage, slow degradation stage and no apparent toxicity was observed after AZ-HECTS hydrogels implanted into rats, and tissue inflammation was slighter, which indicated favorable biological safety. Furthermore, AZ-HECTS hydrogels was loaded with heparin, and released 50% of heparin accumulated 14d. AZ-HECTS-heparin hydrogels showed inhibitory effects on L929, and pro-growth functions within vascular endothelial cells seeded on the hydrogels, meanwhile a positive influence on vascular endothelial growth factor expression. In conclusion, AZ-HECTS hydrogels possessed favorable biocompatibility and biodegradability and had good potential as drug carrier. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lethal photosensitization of biofilm-grown bacteria

NASA Astrophysics Data System (ADS)

Wilson, Michael

1997-12-01

Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

Organic Aerosol Formation Photoenhanced by the Formation of Secondary Photo-sensitizers in ageing Aerosols

NASA Astrophysics Data System (ADS)

Aregahegn, Kifle; Nozière, Barbara; George, Christian

2013-04-01

Humankind is facing a changing environment possibly due to anthropogenic stress on the atmosphere. In this context, aerosols play a key role by affecting the radiative climate forcing, hydrological cycle, and by their adverse effect on health. The role of organic compounds in these processes is however still poorly understood because of their massive chemical complexity and numerous transformations. This is particularly true for Secondary Organic Aerosol (SOA), which are produced in the atmosphere by organic gases. Traditionally, the driving forces for SOA growth is believed to be the partitioning onto aerosol seeds of condensable gases, either emitted primarily or resulting from the gas phase oxidation of organic gases. However, even the most up-to-date models based on such mechanisms can not account for the SOA mass observed in the atmosphere, suggesting the existence of other, yet unknown formation processes. The present study shows experimental evidence that particulate phase chemistry produces photo-sensitizers that lead to photo-induced formation and growth of secondary organic aerosol in the near UV and the presence of volatile organic compounds (VOC) such as terpenes. By means of an aerosol flow tube reactor equipped with Scanning Mobility Particle Sizer (SMPS) having Kr-85 source aerosol neutralizer, Differential Mobility Analyser (DMA) and Condensation Particle Sizer (CPC), we identified that traces of the aerosol phase product of glyoxal chemistry as is explained in Gallway et al., and Yu et al., namely imidazole-2-carboxaldehyde (IC) is a strong photo-sensitizer when irradiated by near-UV in the presence of volatile organic compounds such as terpenes. Furthermore, the influence of pH, type and concentration of VOCs, composition of seed particles, relative humidity and irradiation intensity on particle growth were studied. This novel photo-sensitizer contributed to more than 30% of SOA growth in 19min irradiation time in the presence of terpenes in the

Photochemical predictive analysis of photodynamic therapy with non-homogeneous topical photosensitizer distribution in dermatological applications

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.

2010-04-01

Photodynamic Therapy (PDT) is a therapeutic technique widely used in dermatology to treat several skin pathologies. It is based in topical or systemic delivery of photosensitizing drugs followed by irradiation with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell necrosis. In this work we present a PDT model that tries to predict the photodynamic effect on the skin with a topically administered photosensitizer. The time dependent inhomogeneous distribution of the photoactive compound protoporphyrin IX (PpIX) is calculated after obtaining its precursor distribution (Methyl aminolevulinate, MAL) which depends on the drug permeability, diffusion properties of the skin, incubation time and conversion efficiency of MAL to PpIX. Once the optical energy is obtained by means of the Beer Lambert law, a photochemical model is employed to estimate the concentration of the different molecular compounds taking into account the electronic transitions between molecular levels and particles concentrations. The results obtained allow us to know the evolution of the cytotoxic agent in order to estimate the necrotic area adjusting parameters such as the optical power, the photosensitizer concentration, the incubation and exposition time or the diffusivity and permeability of the tissue.

Applicability of new degradable hypericin-polymer-conjugates as photosensitizers: principal mode of action demonstrated by in vitro models.

PubMed

Feinweber, Daniela; Verwanger, Thomas; Brüggemann, Oliver; Teasdale, Ian; Krammer, Barbara

2014-11-01

Two series of water soluble novel conjugates of the photosensitizer hypericin were prepared and evaluated for their use as agents for photodynamic therapy, with covalently and non-covalently loaded hypericin on functionalised, hydrolytically degradable inorganic-organic hybrid polyphosphazenes. The conjugates showed excellent aqueous solubility and similar fluorescence spectra to pristine hypericin. Detailed in vitro investigations revealed that the substances were non-toxic in the dark over a wide concentration range, but displayed phototoxicity upon irradiation. Cell uptake studies showed rapid uptake with localization of hypericin observed in endoplasmic reticulum, Golgi complex and particularly in the lysosomes. Furthermore, a DNA fragmentation assay revealed that the photosensitizer conjugates are efficient inducers of apoptosis with some tumor cell selectivity caused by faster and enhanced accumulation in A431 than in HaCaT cells, and thus a moderately higher phototoxicity of A431 compared to HaCaT cells. These novel photosensitizer conjugates hence represent viable hydrolytically degradable alternatives for the advanced delivery of hypericin.

Sunlight exposure behaviour and vitamin D status in photosensitive patients: longitudinal comparative study with healthy individuals at U.K. latitude.

PubMed

Rhodes, L E; Webb, A R; Berry, J L; Felton, S J; Marjanovic, E J; Wilkinson, J D; Vail, A; Kift, R

2014-12-01

Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown. To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors. This was a longitudinal prospective cohort study (53·5°N) examining year-round 25-hydroxyvitamin D [25(OH)D] levels, sun-exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109). Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL(-1); 50 nmol L(-1)) and even deficient (< 10 ng mL(-1); 25 nmol L(-1)) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% [95% confidence interval (CI) 4-29] in summer (P = 0·02) and 25% (95% CI 7-39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 μg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 μg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3-7) and 9% (95% CI 5-12), respectively (both P < 0·001). Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians. �

The Fowler-Nordheim behavior and mechanism of photo-sensitive field from SnS{sub 2} nanosheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suryawanshi, Sachin R.; Chaudhari, Nilima S.; Warule, Sambhaji S.

2015-06-24

Here in, we report photo-sensitive field emission measurements of SnS{sub 2} nanosheets at base pressure of ∼1×10{sup −8} mbar are reported. The nonlinear Fowler-Nordheim (F-N) plot is elucidate according to a (F-N) model of calculation based on shift in a saturation of conduction band current density after light illumination and prevalence of valence band current density at high electric field values. The model of calculation suggests that the slope variation before and after visible light illumination of the F-N plot, in the high-field and low-field regions, does not depend on the magnitude of saturation but also depend on charge carriermore » (electron) concentration get increased in conduction band. The F-N model of calculation is important for the fundamental understanding of the photo-sensitive field emission mechanism of semiconducting SnS{sub 2}. The replicate F-N plots exhibit similar features to those observed experimentally. The model calculation suggests that the nonlinearity of the F-N plot is a characteristic of the photo-enhanced energy band structure of the photo-sensitive semiconductor material.« less

Imaging a photodynamic therapy photosensitizer in vivo with a time-gated fluorescence tomography system

NASA Astrophysics Data System (ADS)

Mo, Weirong; Rohrbach, Daniel; Sunar, Ulas

2012-07-01

We report the tomographic imaging of a photodynamic therapy (PDT) photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in vivo with time-domain fluorescence diffuse optical tomography (TD-FDOT). Simultaneous reconstruction of fluorescence yield and lifetime of HPPH was performed before and after PDT. The methodology was validated in phantom experiments, and depth-resolved in vivo imaging was achieved through simultaneous three-dimensional (3-D) mappings of fluorescence yield and lifetime contrasts. The tomographic images of a human head-and-neck xenograft in a mouse confirmed the preferential uptake and retention of HPPH by the tumor 24-h post-injection. HPPH-mediated PDT induced significant changes in fluorescence yield and lifetime. This pilot study demonstrates that TD-FDOT may be a good imaging modality for assessing photosensitizer distributions in deep tissue during PDT monitoring.

Highly reliable photosensitive organic-inorganic hybrid passivation layers for a-InGaZnO thin-film transistors

NASA Astrophysics Data System (ADS)

Bermundo, Juan Paolo; Ishikawa, Yasuaki; Yamazaki, Haruka; Nonaka, Toshiaki; Fujii, Mami N.; Uraoka, Yukiharu

2015-07-01

We report the fabrication of a photosensitive hybrid passivation material on amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs) that greatly enhance its stability and improve its electrical characteristics. The hybrid passivation based on polysilsesquioxane is transparent and fabricated using a simple solution process. Because the passivation is photosensitive, dry etching was never performed during TFT fabrication. TFTs passivated with this material had a small threshold voltage shift of 0.5 V during positive bias stress, 0.5 V during negative bias stress, and -2.5 V during negative bias illumination stress. Furthermore, TFTs passivated by this layer were stable after being subjected to high relative humidity stress — confirming the superb barrier ability of the passivation. Analysis of secondary ion mass spectrometry showed that a large amount of hydrogen, carbon, and fluorine can be found in the channel region. We show that both hydrogen and fluorine reduced oxygen vacancies and that fluorine stabilized weak oxygen and hydroxide bonds. These results demonstrate the large potential of photosensitive hybrid passivation layers as effective passivation materials.

Coexistence of wave propagation and oscillation in the photosensitive Belousov-Zhabotinsky reaction on a circular route.

PubMed

Nakata, Satoshi; Morishima, Sayaka; Ichino, Takatoshi; Kitahata, Hiroyuki

2006-12-21

The photosensitive Belousov-Zhabotinsky (BZ) reaction was investigated on a circular ring, which was drawn using computer software and then projected on a film soaked with BZ solution using a liquid-crystal projector. Under the initial conditions, a chemical wave propagated with a constant velocity on the black ring under a bright background. When the background was rapidly changed to dark, coexistence of the oscillation on part of the ring and propagation of the chemical wave on the other part was observed. These experimental results are discussed in relation to the nature of the photosensitive BZ reaction and theoretically reproduced based on a reaction-diffusion system using the modified Oregonator model.

Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity.

PubMed

Yao, Yongxue; Harrison, Kathleen A; Al-Hassani, Mohammed; Murphy, Robert C; Rezania, Samin; Konger, Raymond L; Travers, Jeffrey B

2012-03-16

To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity.

Location of Varying Hydrophobicity Zinc(II) Phthalocyanine-Type Photosensitizers in Methoxy Poly(ethylene oxide) and Poly(l-lactide) Block Copolymer Micelles Using 1H NMR and XPS Techniques.

PubMed

Lamch, Łukasz; Tylus, Włodzimierz; Jewgiński, Michał; Latajka, Rafał; Wilk, Kazimiera A

2016-12-15

Hydrophobic zinc(II) phthalocyanine-type derivatives, solubilized in polymeric micelles (PMs), provide a befitting group of so-called nanophotosensitizers, suitable for a variety of photodynamic therapy (PDT) protocols. The factors that influence the success of such products in PDT are the location of the active cargo in the PMs and the nanocarrier-enhanced ability to safely interact with biological systems and fulfill their therapeutic functions. Therefore, the aim of this work was to determine the solubilization loci of three phthalocyanines of varying hydrophobicity, i.e., zinc(II) phthalocyanine (ZnPc), along with its tetrasulfonic acid (ZnPc-sulfo 4 ) and perfluorinated (ZnPcF 16 ) derivatives, loaded in polymeric micelles of methoxy poly(ethylene oxide)-b-poly(l-lactide) (mPEG-b-PLLA), by means of 1 H nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) combined with ion sputtering. Furthermore, the microenvironment influence upon the chemical and physical status of the solubilized cargo in PMs, expressed by photobleaching and reactive oxygen species (ROS) generation comparing to the same properties of native cargoes in solution, was also evaluated and discussed in regards to the probing location data. The studied phthalocyanine-loaded PMs exhibited good physical stability, high drug-loading efficiency, and a size of less than ca. 150 nm with low polydispersity indices. The formation of polymeric micelles and the solubilization locus were investigated by 1 H NMR and XPS. ZnPc localized within the PM core, whereas both ZnPcF 16 and ZnPc-sulfo 4 - in the corona of PMs. We proved that the cargo locus is crucial for the photochemical properties of the studied phthalocyanines; the increase in photostability and ability to generate ROS in micellar solution compared to free photosensitizer was most significant for the photosensitizer in the PM core. Our results indicate the role of the cargo location in the PM microenvironment and demonstrate

Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as target-specific photosensitizer.

PubMed

Zheng, Gang; Li, Hui; Zhang, Min; Lund-Katz, Sissel; Chance, Britton; Glickson, Jerry D

2002-01-01

To target tumors overexpressing low-density lipoprotein receptors (LDLr), a pyropheophorbide cholesterol oleate conjugate was synthesized and successfully reconstituted into the low-density lipoprotein (LDL) lipid core. Laser scanning confocal microscopy studies demonstrated that this photosensitizer-reconstituted LDL can be internalized via LDLr by human hepatoblastoma G(2) (HepG(2)) tumor cells.

Analysis of the in vitro and in vivo effects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives.

PubMed

Fidanzi-Dugas, Chloë; Liagre, Bertrand; Chemin, Guillaume; Perraud, Aurélie; Carrion, Claire; Couquet, Claude-Yves; Granet, Robert; Sol, Vincent; Léger, David Yannick

2017-07-01

Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine Transport System (PTS), they may enable PS to specifically target cancer cells. Here, we investigated whether new protoporphyrin IX-polyamine derivatives were effective PS against prostate cancer and whether PA increased PDT specificity after 630nm irradiation. CHO and CHO-MG cells (differing in their PTS activity) were used to assess efficacy of polyamine vectorization. MTT assays were performed on human prostate non-malignant (RWPE-1) and malignant (PC-3, DU 145 and LNCaP) cell lines to test PS phototoxicity. ROS generation, DNA fragmentation and cell signalling were assessed by ELISA/EIA, western-blots and gel shift assays. Finally, PS effects were studied on tumor growth in nude mice. Our PS were more effective on cancer cells compared to non-malignant cells and more effective than PpIX alone. PpIX-PA generated ROS production involved in induction of apoptotic intrinsic pathways. Different pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, and NF-κB but activated p38/COX-2/PGE 2 pathways which were not implicated in apoptosis resistance in our model. In vivo experiments showed PpIX-PA efficacy was greater than results obtained with PpIX. All together, our results showed that PpIX-PA exerted its maximum effects without activating resistance pathways and appears to be a good candidate for prostate cancer PDT treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Photo-induced oxidative damage to dissolved free amino acids by the photosensitizer polycyclic musk tonalide: Transformation kinetics and mechanisms.

PubMed

Fang, Hansun; Gao, Yanpeng; Wang, Honghong; Yin, Hongliang; Li, Guiying; An, Taicheng

2017-05-15

Residue from the polycyclic musks (PCMs) in household and personal care products may harm human beings through skin exposure. To understand the health effects of PCMs when exposed to sunlight at molecular level, both experimental and computational methods were employed to investigate the photosensitized oxidation performance of 19 natural amino acids, the most basic unit of life. Results showed that a typical PCM, tonalide, acts as a photosensitizer to significantly increase photo-induced oxidative damage to amino acids. Both common and exceptional transformation pathways occurred during the photosensitization damage of amino acids. Experimental tests further identified the different mechanisms involved. The common transformation pathway occurred through the electron transfer from α amino-group of amino acids, accompanying with the formation of O 2 •- . This pathway was controlled by the electronic density of N atom in α amino-group. The exceptional transformation pathway was identified only for five amino acids, mainly due to the reactions with reactive oxygen species, e.g. 1 O 2 and excited triplet state molecules. Additionally, tonalide photo-induced transformation products could further accelerate the photosensitization of all amino acids with the common pathway. This study may support the protection of human health, and suggests the possible need to further restrict polycyclic musks use. Copyright © 2017 Elsevier Ltd. All rights reserved.

Towards dosimetry for photodynamic diagnosis with the low-level dose of photosensitizer.

PubMed

Buzalewicz, Igor; Hołowacz, Iwona; Ulatowska-Jarża, Agnieszka; Podbielska, Halina

2017-08-01

Contemporary medicine does not concern the issue of dosimetry in photodynamic diagnosis (PDD) but follows the photosensitizer (PS) producers recommendation. Most preclinical and clinical PDD studies indicate a considerable variation in the possibility of visualization and treatment, as e.g. in case of cervix lesions. Although some of these variations can be caused by the different histological subtypes or various tumor geometries, the issue of varying PS concentration in the tumor tissue volume is definitely an important factor. Therefore, there is a need to establish the objective and systematic PDD dosimetry protocol regarding doses of light and photosensitizers. Four different irradiation sources investigated in PDD (literature) were used for PS excitation. The PS luminescence was examined by means of the non-imaging (spectroscopic) and imaging (wide- and narrow-field of view) techniques. The methodology for low-level intensity photoluminescence (PL) characterization and dedicated image processing algorithm for PS luminescence images analysis were proposed. Further, HeLa cells' cultures penetration by PS was studied by a confocal microscopy. Reducing the PS dose with the choice of proper photoexcitation conditions decreases the PDD procedure costs and the side effects, not affecting the diagnostic efficiency. We determined in vitro the minimum incubation time and photosensitizer concentration of Photolon for diagnostic purposes, for which the Photolon PL can still be observed. It was demonstrated that quantification of PS concentration, choice of proper photoexcitation source, appropriate adjustment of light dose and PS penetration of cancer cells may improve the low-level luminescence photodynamic diagnostics performance. Practical effectiveness of the PDD strongly depends on irradiation source parameters (bandwidth, maximum intensity, half-width) and their optimization is the main conditioning factor for low-level intensity and low-cost PDD. Copyright © 2017

Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

Triplet photosensitizers: from molecular design to applications.

PubMed

Zhao, Jianzhang; Wu, Wanhua; Sun, Jifu; Guo, Song

2013-06-21

Triplet photosensitizers (PSs) are compounds that can be efficiently excited to the triplet excited state which subsequently act as catalysts in photochemical reactions. The name is originally derived from compounds that were used to transfer the triplet energy to other compounds that have only a small intrinsic triplet state yield. Triplet PSs are not only used for triplet energy transfer, but also for photocatalytic organic reactions, photodynamic therapy (PDT), photoinduced hydrogen production from water and triplet-triplet annihilation (TTA) upconversion. A good PS should exhibit strong absorption of the excitation light, a high yield of intersystem crossing (ISC) for efficient production of the triplet state, and a long triplet lifetime to allow for the reaction with a reactant molecule. Most transition metal complexes show efficient ISC, but small molar absorption coefficients in the visible spectral region and short-lived triplet excited states, which make them unsuitable as triplet PSs. One obstacle to the development of new triplet PSs is the difficulty in predicting the ISC of chromophores, especially of organic compounds without any heavy atoms. This review article summarizes some molecular design rationales for triplet PSs, based on the molecular structural factors that facilitate ISC. The design of transition metal complexes with large molar absorption coefficients in the visible spectral region and long-lived triplet excited states is presented. A new method of using a spin converter to construct heavy atom-free organic triplet PSs is discussed, with which ISC becomes predictable, C60 being an example. To enhance the performance of triplet PSs, energy funneling based triplet PSs are proposed, which show broadband absorption in the visible region. Applications of triplet PSs in photocatalytic organic reactions, hydrogen production, triplet-triplet annihilation upconversion and luminescent oxygen sensing are briefly introduced.

Photosensitized H2 Production Using a Zinc Porphyrin-Substituted Protein, Platinum Nanoparticles, and Ascorbate with No Electron Relay: Participation of Good's Buffers.

PubMed

Clark, Emily R; Kurtz, Donald M

2017-04-17

Development of efficient light-driven splitting of water, 2H 2 O → 2H 2 + O 2 , often attempts to optimize photosensitization of the reductive and oxidative half-reactions individually. Numerous homogeneous and heterogeneous systems have been developed for photochemical stimulation of the reductive half reaction, 2H + + 2e - → H 2 . These systems generally consist of various combinations of a H + reduction catalyst, a photosensitizer (PS), and a "sacrificial" electron donor. Zinc(II)-porphyrins (ZnPs) have frequently been used as PSs for H 2 generation, but they are subject to various self-quenching processes in aqueous solutions. Colloidal platinum in nanoparticle form (Pt NP) is a classical H + reduction catalyst using ZnP photosensitizers, but efficient photosensitized H 2 generation requires an electron relay molecule between ZnP and Pt NP. The present report describes an aqueous system for visible (white) light-sensitized generation of H 2 using a protein-embedded Zn(II)-protoporphyrin IX as PS and Pt NP as H + reduction catalyst without an added electron relay. This system operated efficiently in piperazino- and morpholino-alkylsulfonic acid (Good's buffers), which served as sacrificial electron donors. The system also required ascorbate at relatively modest concentrations, which stabilized the Zn(II)-protoporphyrin IX against photodegradation. In the absence of an electron relay molecule, the photosensitized H 2 generation must involve formation of at least a transient complex between a protein-embedded Zn(II)-protoporphyrin IX species and Pt NP.

DNA Photosensitization by an "Insider": Photophysics and Triplet Energy Transfer of 5-Methyl-2-pyrimidone Deoxyribonucleoside.

PubMed

Bignon, Emmanuelle; Gattuso, Hugo; Morell, Christophe; Dumont, Elise; Monari, Antonio

2015-08-03

The main chromophore of (6-4) photoproducts, namely, 5-methyl-2-pyrimidone (Pyo), is an artificial noncanonical nucleobase. This chromophore has recently been reported as a potential photosensitizer that induces triplet damage in thymine DNA. In this study, we investigate the spectroscopic properties of the Pyo unit embedded in DNA by means of explicit solvent molecular-dynamics simulations coupled to time-dependent DFT and quantum-mechanics/molecular-mechanics techniques. Triplet-state transfer from the Pyo to the thymine unit was monitored in B-DNA by probing the propensity of this photoactive pyrimidine analogue to induce a Dexter-type triplet photosensitization and subsequent DNA damage. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photosensitizing effects of nanometer TiO2 on chlorothalonil photodegradation in aqueous solution and on the surface of pepper.

PubMed

Tan, Yong Qiang; Xiong, Hai Xia; Shi, Tao Zhong; Hua, Ri Mao; Wu, Xiang Wei; Cao, Hai Qun; Li, Xue De; Tang, Jun

2013-05-29

The present study examined the effects of anatase nanometer TiO2 on photochemical degradation of chlorothalonil in aqueous solution and on the plant surface. Results showed that nanometer TiO2 exhibited a strong photosensitizing effect on the degradation of chlorothalonil both in aqueous solution and on the surface of green pepper. The photosensitization rate was the highest in the sunlight compared to illumination under high-pressure mercury and UV lamps. Use of distinct hydroxyl radical scavengers indicated that nanometer TiO2 acted by producing hydroxyl radicals with strong oxidizing capacity. Notably, nanometer TiO2 facilitated complete photodegradation of chlorothalonil with no detectable accumulation of the intermediate chlorothalonil-4-hydroxy. Nanometer TiO2 was also active on the surface of green pepper under natural sunlight both inside and outside of plastic greenhouse. These results together suggest that nanometer TiO2 can be used as a photosensitizer to accelerate degradation of the pesticides under greenhouse conditions.

Attaching naphthalene derivatives onto BODIPY for generating excited triplet state and singlet oxygen: Tuning PET-based photosensitizer by electron donors

NASA Astrophysics Data System (ADS)

Zhang, Xian-Fu; Feng, Nan

2018-01-01

meso-Naphthalene substituted BODIPY compounds were prepared in a facile one pot reaction. The naphthalene functionalization of BODIPY leads up to a 5-fold increase in the formation efficiency of excited triplet state and singlet oxygen in polar solvents. Steady state and time resolved fluorescence, laser flash photolysis, and quantum chemistry methods were used to reveal the mechanism. All measured data and quantum chemical results suggest that these systems can be viewed as electron donor-acceptor (D-A) pair (BODIPY acts as the acceptor), photoinduced charge transfer (PCT) or photoinduced electron transfer (PET) occurs upon photo excitation (D-A + hν → Dδ +-Aδ -, 0 < δ ≤ 1), and the charge recombination induced the formation of triplet state (Dδ +-Aδ - → D-A (T1). These novel PCT- or PET-based photosensitizers (PSs) show different features from traditional PSs, such as the strong tunability by facile structural modification and good selectivity upon medium polarity. The new character for this type of PSs can lead to important applications in organic oxygenation reactions and photodynamic therapy of tumors.

Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

NASA Astrophysics Data System (ADS)

Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

1998-07-01

Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

Polycrystalline BiFeO{sub 3} thin film synthesized via sol-gel assisted spin coating technique for photosensitive application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogle, K. A., E-mail: kashinath.bogle@gmail.com; Narwade, R. D.; Mahabole, M. P.

2016-05-06

We are reporting photosensitivity property of BiFeO{sub 3} thin film under optical illumination. The thin film used for photosensitivity work was fabricated via sol-gel assisted spin coating technique. I-V measurements on the Cu/BiFeO{sub 3}/Al structure under dark condition show a good rectifying property and show dramatic blue shit in threshold voltage under optical illumination. The microstructure, morphology and elemental analysis of the films were characterized by using XRD, UV-Vis, FTIR, SEM and EDS.

Doxorubicin-loaded photosensitive magnetic liposomes for multi-modal cancer therapy.

PubMed

Shah, Saqlain A; Aslam Khan, M U; Arshad, M; Awan, S U; Hashmi, M U; Ahmad, N

2016-12-01

Multifunctional magnetic nanosystems have attracted an enormous attention of researchers for their potential applications in cancer diagnostics and therapy. The localized nanotherapies triggered by the external stimuli, like magnetic fields and visible light, are significant in clinical applications. We report a liposomal system that aims to treat cancer by magnetic hyperthermia, photodynamic therapy and chemotherapy simultaneously. The liposomes enclose clinically used photosensitizer m-THPC (Foscan) and anti-cancer drug doxorubicin, in its hydrophobic lipid bilayers, and contains magnetite nanoparticles in hydrophilic core. Three different sizes of magnetic nanoparticles (10, 22 and 30nm) and liposomes (40, 70 and 110nm) were used in this study. Magnetite single domain nanoparticles forming the magnetic core were superparamagnetic but liposomes expressed slight coercivity and hysteresis due to the clustering of nanoparticles in the core. This enhanced the heating efficiency (specific power loss) of the liposomes under an AC field (375kHz, 170Oe). Cell viability and toxicity were studied on HeLa cells using MTT assay and proteomic analysis. Confocal and fluorescence microscopy were used to study the photosensitizer's profile and cells response to combined therapy. It revealed that combined therapy almost completely eliminated the cancer cells as opposed to the separate treatments. Magnetic hyperthermia and photodynamic therapies were almost equally effective whereas chemotherapy showed the least effect. Copyright © 2016. Published by Elsevier B.V.

Effect of variation in indium concentration on the photosensitivity of chlorine doped In{sub 2}S{sub 3} thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherian, Angel Susan; Kartha, C. Sudha; Vijayakumar, K. P.

2014-01-28

Consequence of variation in Indium concentration in chlorine doped In2S{sub 3} thin films deposited by spray pyrolysis technique was studied. Chlorine was incorporated in the spray solution, using HCl and Indium concentration was varied by adjusting In/S ratio Interestingly, the photo response of all chlorine doped samples augmented compared to pristine samples; but the highest photosensitivity value of ∼2300 was obtained only when 36ml 0.5M HCl was added to the solution of In{sub 2}S{sub 3} having In/S=2/8. It was also observed that samples with high photosensitivity possess higher band gap and variation in sub band gap absoption levels were observedmore » with increase in Indium concentration. The present study proved that concentration of Indium plays an important role in controlling the crystallinity and photosensitivity of chlorine doped samples.« less

Design and syntheses of MMP inhibitors and photosensitive lipid nanoparticle formulations for drug delivery

NASA Astrophysics Data System (ADS)

Subramaniam, Rajesh

Drug administration without any compromise to the quality of life and lifespan is the ideal goal for disease management. The molecular mechanisms of several pathologies have shown that site-specific delivery of target-specific drugs seems to be a promising avenue to achieve this goal. This thesis describes the initial steps that we have taken toward that goal. Matrix metalloproteinases (MMPs) are a family of about 23 isozymes in humans that were actively targeted for treating a multitude of pathologies. Clinical studies carried out on cancer patients have revealed the complexity of the working of this enzyme family and necessitated the development of isozyme-specific MMP inhibitors. Our studies toward the development of isozyme-specific inhibitors have resulted in the development of several inhibitors that seem to be selective toward some MMP isozymes. Our understanding on the molecular mechanism that confers this selectivity is documented in this thesis. Another aspect of discussion in the thesis is the development of photosensitive liposomes for drug delivery that could be triggered to release the drug by irradiation with light of appropriate wavelength. Development of such delivery vehicles, in principle, would confer external spatiotemporal control on drug delivery. This could potentially lead to better disease management by minimizing side effects and enhancing patient compatibility. The thesis discusses our attempts toward the development of photosensitive liposomes. These liposomes incorporated a photosensitive lipid (PSL) that would be cleaved upon irradiation with UV light, causing liposomal destabilization and release of the enclosed drug. The discussion includes: (i) the syntheses of the PSLs, (ii) formulation of the photosensitive liposomes that contained a model drug, (iii) light-mediated release of the drug and (iv) the mechanism of photocleavage of the PSL that leads to content release from liposomes. The thesis concludes with suggestions toward the

Quenching of porous silicon photoluminescence by molecular oxygen and dependence of this phenomenon on storing media and method of preparation of pSi photosensitizer

NASA Astrophysics Data System (ADS)

Balaguer, María; Matveeva, Eugenia

2010-10-01

The quenching of porous silicon photoluminescence (pSi PL) by molecular oxygen has been studied in different storing media in an attempt to clarify the mechanism of the energy transfer from the silicon photosensitizer to the oxygen acceptor. Luminescent materials have been prepared by two methods: electrochemical anodizing and chemical etching. Different structural forms were used: porous layers on silicon wafer and two kinds of differently prepared powder. Dry air and liquid water were employed as storing media; quenching behaviour was under observation until total degradation of quenching properties. Singlet oxygen molecules generation through energy transfer from photoluminescent pSi was the only photosensitizing mechanism observed under dry gas conditions. This PL quenching process was preferentially developed at 760 nm (1.63 eV) that corresponds to the formation of the 1Σ singlet oxygen state. Oxidation of the pSi photosensitizer was the main factor that led to its total deactivation in a time scale of few weeks. Regarding water medium, different photosensitizing behaviour was observed. In watery conditions, two preferred energy levels were found: the one detected in dry gas and another centred at approximately 2.2 eV (550 nm). Formation of reactive oxygen species (ROS) different from singlet oxygen, such as superoxide anion or superoxide radical, can be responsible for the second one. This second quenching process developed gradually after the initial contact of pSi photosensitizer with water and then degraded. The process lasted only several hours. Therefore, functionalization of the pSi photosensitizer is probably required to stabilize its PL and quenching properties in the watery physiological conditions required for biomedical applications.

Photosensitized electron transport across lipid vesicle walls: Enhancement of quantum yield by ionophores and transmembrane potentials

PubMed Central

Laane, Colja; Ford, William E.; Otvos, John W.; Calvin, Melvin

1981-01-01

The photosensitized reduction of heptylviologen in the bulk aqueous phase of phosphatidylcholine vesicles containing EDTA inside and a membrane-bound tris(2,2′-bipyridine)ruthenium(2+) derivative is enhanced by a factor of 6.5 by the addition of valinomycin in the presence of K+. A 3-fold stimulation by gramicidin and carbonyl cyanide m-chlorophenylhydrazone is observed. The results suggest that, under these conditions, the rate of photoinduced electron transfer across vesicle walls in the absence of ion carriers is limited by cotransport of cations. The rate of electron transfer across vesicle walls could be influenced further by generating transmembrane potentials with K+ gradients in the presence of valinomycin. When vesicles are made with transmembrane potentials, interior more negative, the quantum yield of heptylviologen reduction is doubled, and, conversely, when vesicles are made with transmembrane potentials, interior more positive, the quantum yield is decreased and approaches the value found in the absence of valinomycin. PMID:16593002

Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.

PubMed

Gyenge, Emina Besic; Lüscher, Daniel; Forny, Patrick; Antoniol, Martina; Geisberger, Georg; Walt, Heinrich; Patzke, Greta; Maake, Caroline

2013-01-01

The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso-tetrahydroxyphenyl chlorin (mTHPC) derivative, with focus on their 1:1 mixture, on head and neck squamous cell carcinoma cell lines. Absorption, excitation and photobleaching were monitored using fluorescence spectrometry, showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo-stability. Singlet oxygen yield for light-activated mTHPC was Φ(Δ) = 0.66, for hypericin Φ(Δ) = 0.25 and for the mixture Φ(Δ) = ~0.4. A linear increase of singlet oxygen yield for mTHPC and the mixture was found, whereas hypericin achieved saturation after 35 min. Reactive oxygen species fluorescence was only visible after hypericin and mixture-induced PDT. Cell viability was also more affected with these two treatment options under the selected conditions. Examination of death pathways showed that hypericin-mediated cell death was apoptotic, with mTHPC necrotic and the 1:1 mixture showed features of both. Changes in gene expression after PDT indicated strong up-regulation of selected heat-shock proteins. The application of photosensitizer mixtures with the features of reduced dark toxicity and combined apoptotic and necrotic cell death may be beneficial in clinical PDT. This will be the focus of our future investigations. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

In vitro assessment of skin sensitization, photosensitization and phototoxicity potential of commercial glyphosate-containing formulations.

PubMed

de Ávila, Renato Ivan; Teixeira, Gabriel Campos; Veloso, Danillo Fabrini Maciel Costa; Moreira, Larissa Cleres; Lima, Eliana Martins; Valadares, Marize Campos

2017-12-01

This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm 2 ) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activatable albumin-photosensitizer nanoassemblies for triple-modal imaging and thermal-modulated photodynamic therapy of cancer.

PubMed

Hu, Dehong; Sheng, Zonghai; Gao, Guanhui; Siu, Fungming; Liu, Chengbo; Wan, Qian; Gong, Ping; Zheng, Hairong; Ma, Yifan; Cai, Lintao

2016-07-01

Photodynamic therapy (PDT) is a noninvasive and effective approach for cancer treatment. The main bottlenecks of clinical PDT are poor selectivity of photosensitizer and inadequate oxygen supply resulting in serious side effects and low therapeutic efficiency. Herein, a thermal-modulated reactive oxygen species (ROS) strategy using activatable human serum albumin-chlorin e6 nanoassemblies (HSA-Ce6 NAs) for promoting PDT against cancer is developed. Through intermolecular disulfide bond crosslinking and hydrophobic interaction, Ce6 photosensitizer is effectively loaded into the HSA NAs, and the obtained HSA-Ce6 NAs exhibit excellent reduction response, as well as enhanced tumor accumulation and retention. By the precision control of the overall body temperature instead of local tumor temperature increasing from 37 °C to 43 °C, the photosensitization reaction rate of HSA-Ce6 NAs increases 20%, and the oxygen saturation of tumor tissue raise 52%, significantly enhancing the generation of ROS for promoting PDT. Meanwhile, the intrinsic fluorescence and photoacoustic properties, and the chelating characteristic of porphyrin ring can endow the HSA-Ce6 NAs with fluorescence, photoacoustic and magnetic resonance triple-modal imaging functions. Upon irradiation of low-energy near-infrared laser, the tumors are completely suppressed without tumor recurrence and therapy-induced side effects. The robust thermal-modulated ROS strategy combined with albumin-based activatable nanophotosensitizer is highly potential for multi-modal imaging-guided PDT and clinical translation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pronounced photosensitivity of molecular [Ru(bpy)2(OSO)]+ solutions based on two photoinduced linkage isomers.

PubMed

Dieckmann, Volker; Eicke, Sebastian; Rack, Jeffrey J; Woike, Theo; Imlau, Mirco

2009-08-17

Photosensitive properties of [Ru(bpy)(2)(OSO)] PF(6) dissolved in propylene carbonate originating from photoinduced linkage isomerism have been studied by temperature and exposure dependent transmission and UV/Vis absorption spectroscopy. An exceeding photochromic photosensitivity of S = (63 +/- 10) x 10(3) cm l J(-1) mol(-1) is determined. It is attributed to a maximum population of 100% molecules in the photoinduced isomers, a unique absorption cross section per molecule and a very low light exposure of Q(0) = (0.25 +/- 0.03) Ws cm(-2) for isomerism. Relaxation studies of O-bonded to S-bonded isomers at different temperatures verify the existence of two distinct structures of linkage isomers determined by the activation energies of E(A,1) = (0.76 +/- 0.08) eV and E(A,2) = (1.00 +/- 0.14) eV.

Targeted two-photon PDT photo-sensitizers for the treatment of subcutaneous tumors

NASA Astrophysics Data System (ADS)

Spangler, C. W.; Rebane, A.; Starkey, J.; Drobizhev, M.

2009-06-01

New porphyrin-based photo-sensitizers have been designed, synthesized and characterized that exhibit greatly enhanced intrinsic two-photon absorption. These new photo-sensitizers have been incorporated into triad formulations that also incorporate Near-infrared (NIR) imaging agents, and small-molecule targeting agents that direct the triads to cancerous tumors' over-expressed receptor sites. PDT can be initiated deep into the tissue transparency window at 780-800 nm utilizing a regeneratively amplified Ti:sapphire laser using 100-150 fs pulses of 600-800 mW. Human tumor xenografts of human breast cancer (MDA-MB-231) and both small SCLC (NCI-H69) and NSCLC (A-459) have been successfully treated using octreotate targeting of over-expressed SST2 receptors. In particular, the lung cancer xenografts can be successfully treated by irradiating from the side of the mouse opposite the implanted tumor, thereby passing through ca. 2 cm of mouse skin, tissue and organs with no discernible damage to healthy tissue while causing regression in the tumors. These results suggest a new PDT paradigm for the noninvasive treatment of subcutaneous tumors, including the possibility that the targeting moiety could be matched to individual patient genetic profiles (patient-specific therapeutics).

Excited triplet state of N-(9-methylpurin-6-yl)pyridinium cation as an efficient photosensitizer in the oxidation of sulfur-containing amino acids. Laser flash and steady-state photolysis studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marciniak, B.; Hug, G.L.; Bobrowski, K.

1995-01-11

In this paper, we present and discuss the results of a detailed mechanistic study of the photosensitized oxidation of sulfur-containing amino acids by N-(9-methylpurin-6-yl)pyridinium cations in aqueous solution. The results provide data on the photoreactivity of the pyridinium salts (derived from the purine bases) in the presence of the electron donors such as sulfur-containing organic compounds and give new experimental evidence for the general mechanism of the sensitized photooxidation of thioethers proposed previously. 39 refs., 6 figs., 2 tabs.

Photosensitive response of azobenzene containing films towards pure intensity or polarization interference patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadavalli, Nataraja Sekhar; Santer, Svetlana, E-mail: santer@uni-potsdam.de; Saphiannikova, Marina

2014-08-04

In this paper, we report on differences in the response of photosensitive azobenzene containing films upon irradiation with the intensity or polarization interference patterns. Two materials are studied differing in the molecular weight: an azobenzene-containing polymer and a molecular glass formed from a much smaller molecule consisting of three connected azobenzene units. Topography changes occurring along with the changes in irradiation conditions are recorded using a homemade set-up combining an optical part for generation and shaping of interference patterns and an atomic force microscope for acquiring the kinetics of film deformation. In this way, we could reveal the unique behaviormore » of photosensitive materials during the first few minutes of irradiation: the change in topography is initially driven by an increase in the azobenzene free volume along with the trans-cis isomerization, followed by the mass transport finally resulting in the surface relief grating. This study demonstrates the great potential of our setup to experimentally highlight puzzling processes governing the formation of surface relief gratings.« less

Photosensitivity in the circadian hatching rhythm of the carotenoid-depleted silkworm, Bombyx mori.

PubMed

Sakamoto, K; Shimizu, I

1994-01-01

Silkworms (Bombyx mori) were reared on a carotenoid-deprived artificial diet, and the carotenoid-depleted eggs of the next generation were incubated so that we could observe the effect of the depletion on the circadian rhythm of hatching. The phototactic response curves of newly hatched larvae showed that the visual photosensitivity in ocelli of larvae from the carotenoid-depleted eggs was at least 4 log units lower than that of a carotenoid-rich control group. However, the phase-shift experiment revealed that carotenoid depletion did not reduce the photosensitivity in the hatching rhythm. When the hatching rhythm was generated by exposure to a single light pulse in constant darkness, the first peak in the rhythm of the carotenoid-depleted silkworms occurred significantly earlier than that of the carotenoid-rich group, but the following second peaks of both groups were found at the same time. These results suggest that for the silkworm, carotenoid is not involved in photoreception for the hatching rhythm, but is involved in the timing of hatching.

Analysis of oligonucleotide photoproducts produced by UV-A light and a riboflavin photosensitizer

NASA Astrophysics Data System (ADS)

Gelhaus, Stacy L.; LaCourse, William R.

2004-12-01

DNA damage is caused by a variety of foreign and endogenous compounds. There are endogenous photosensitizers in cells, such as porphyrins and flavins, which may create damage in the presence of UV-A light. Typically, samples are analyzed by 32P-postlabelling and electrophoretic separation or by LC-MS separation and detection. Separation by HPLC is common; however, in all instances, the DNA sample is hydrolyzed down to nucleosides prior to analysis. It will be shown here that ion-pairing reversed phase high performance liquid chromatography (IP-RPLC) has the ability to provide biophysical information concerning the sites of UV-A induced photosensitizer damage on an intact oligonucleotide concurrent with the separation. IP-RPLC is less labor intensive and faster than electrophoretic methods and it is less costly than LC-MS. IP-RPLC can also be used to purify modified oligonucleotides for further use and analysis. This technique is sensitive to the charge, conformation, and sequence characteristics of the nucleic acid sample and may be used to determine the damage or modifications made to DNA by a variety of compounds.

Photophysical and photochemical properties of Bauhinia megalandra (Caesalpinaceae) extracts as new PDT photosensitizer

NASA Astrophysics Data System (ADS)

Vargas Tovar, Franklin R.; Rivas, C.; Estrada, O.; Marcano O., Aristides A.; Echevarria, Lorenzo; Diaz, Yrene; Alexander, I.; Rodriguez, L.; Padron, L.; Rivera, I. R.

2004-10-01

Recently new photosensitizers, chlorophyll "a and b" derivatives, for photodynamic therapy (PDT) have been presented. It already passed complete pre-clinical investigations. This prompted us to carry out an extensive study of photophysical properties of chlorine derivatives, important both for optimization of their clinic applications and for study of mechanisms of chlorine PDT&. The fresh leaves of Bauhinia megalandra (Caesalpinaceae) were extracted with methanol by percolation, and re-extract with a mixture of methanol-water (1:1), the insoluble fraction was then separated by column chromatography [RP18/hexane-ethylacetate (9:1)] to obtain four fractions named 1 to 4. These compounds were identified by NMR data. We found that 3 and 4 efficiently generates singlet oxygen when irradiated with visible light. Detection of the singlet oxygen was fulfilled by its reaction with histidine and detected by bleaching p-nitrosodimethylaniline under 440 nm irradiation. The quantum yields of singlet oxygen determined by us were 0.088 (1), 0.151 (2), 0.219 (3) and 0.301 (4). We measured absorption and fluorescence spectra of compounds 1 to 4 (Mg-chlorophyll-a, Pheophytin, Mg-chlorophyll-b and chlorophyll-b respectively) in different media and in aqueous solutions of human serum albumin. The association constant of the compounds 1, 2, 3 and 4 in the presence of HSA were estimated. The binding and quenching studies suggest that only 1 and 3 may serve as a useful fluorescence probe for structure/function studies of different chlorophyll binding proteins. No photoinduced binding was observed after irradiation by all the studied compounds in presence of human serum albumin.

Shower PUVA: a novel variant of photochemotherapy. Distribution of photosensitivity and accumulation of trioxsalen in the skin.

PubMed

Sánchez Ruderisch, H; Aryee-Boi, J; Schwarz, C; Radenhausen, M; Tebbe, B

2004-01-01

Shower PUVA is a new variant of photochemotherapy suitable for therapy of various skin disorders. Psoralen, e.g. trioxsalen-containing water recirculates in a closed shower system and wets the skin continuously. After showering, whole-body UVA irradiation (320-400 nm) is performed. In order to prove the equal distribution of photosensitivity in vivo minimal phototoxic dose (MPD) was determined in different skin areas of healthy individuals. Additionally, we investigated the accumulation of trioxsalen in psoriasis lesions under the conditions described by quantifying psoralen in scales collected after showering. In a randomized study 20 healthy volunteers (skin type I-III) took showers for 5 and 10 min in trioxsalen (0.27 mg/l)-containing water at 37 degrees C. Immediately afterwards, MPD was tested on the inside of the upper arms and on the buttocks by using a polychromator light source (315-400 nm). The applied UVA doses were 0.06-0.75 J/cm(2) with steps of 0.125 J/cm(2). MPD was evaluated after 72 h. Equal distribution of photosensitivity was defined as equal MPD on the insides of the upper arm and the buttocks (+/-0.125 J/cm(2)). Skin scales of 21 patients with psoriasis were collected by scratching after showering with trioxsalen-containing water (0.27 mg/l) for 5 min. For quantification of trioxsalen in the scales HPLC was performed. An equal distribution of photosensitivity was achieved in 70% (14/20) cases after 10-min showering in trioxsalen-containing water. Showering for 5 min only revealed a 30% (6/20) rate of equal distributed photosensitivity. After 10-min shower time MPD was 0.325 J/cm(2) (median; range: 0.06-0.625 J/cm(2)). The average amount of trioxsalen found in the scales was 2.03 ng/mg scales (range: 0.38-7.2 ng/mg). For shower PUVA using trioxsalen, 10 min shower time is recommended to achieve sufficient distribution of photosensitivity on the skin. Clinical efficacy of shower PUVA can be explained by skin accumulation of trioxsalen which

Area-selective atomic layer deposition of platinum using photosensitive polyimide.

PubMed

Vervuurt, René H J; Sharma, Akhil; Jiao, Yuqing; Kessels, Wilhelmus Erwin M M; Bol, Ageeth A

2016-10-07

Area-selective atomic layer deposition (AS-ALD) of platinum (Pt) was studied using photosensitive polyimide as a masking layer. The polyimide films were prepared by spin-coating and patterned using photolithography. AS-ALD of Pt using poly(methyl-methacrylate) (PMMA) masking layers was used as a reference. The results show that polyimide has excellent selectivity towards the Pt deposition, after 1000 ALD cycles less than a monolayer of Pt is deposited on the polyimide surface. The polyimide film could easily be removed after ALD using a hydrogen plasma, due to a combination of weakening of the polyimide resist during Pt ALD and the catalytic activity of Pt traces on the polyimide surface. Compared to PMMA for AS-ALD of Pt, polyimide has better temperature stability. This resulted in an improved uniformity of the Pt deposits and superior definition of the Pt patterns. In addition, due to the absence of reflow contamination using polyimide the nucleation phase during Pt ALD is drastically shortened. Pt patterns down to 3.5 μm were created with polyimide, a factor of ten smaller than what is possible using PMMA, at the typical Pt ALD processing temperature of 300 °C. Initial experiments indicate that after further optimization of the polyimide process Pt features down to 100 nm should be possible, which makes AS-ALD of Pt using photosensitive polyimide a promising candidate for patterning at the nanoscale.

Tetraphenylporphyrin derivatives possessing piperidine group as potential agents for photodynamic therapy.

PubMed

Liao, Ping-Yong; Gao, Ying-Hua; Wang, Xin-Rong; Bao, Lei-Lei; Bian, Jun; Hu, Tai-Shan; Zheng, Mei-Zhen; Yan, Yi-Jia; Chen, Zhi-Long

2016-12-01

Photodynamic therapy (PDT) is a noninvasive therapeutic and promising procedure in cancer treatment and has attracted considerable attention in recent years. In the present paper, 2-piperidinetetraphenylporphyrin derivatives (P1-P3) conjugated with different substituents (Cl, Me, MeO group) at phenyl position were synthesized via nucleophilic substitution of 2-nitroporphyrin copper derivatives with piperidine by refluxing under a nitrogen atmosphere and then demetalization. The combination of 1 H NMR, 13 C NMR and HR-MS was used to elucidate the identities of them. Their photophysical and photochemical properties, intracellular localization, cytotoxicity in vitro and in vivo against QBC-939 cells were investigated. They have absorption at wavelength about 650nm. All synthesized photosensitizers showed low dark cytotoxicity and comparable with that of hematoporphyrin monomethyl ether (HMME). And they were more phototoxic than HMME to QBC-939 cells in vitro. In bearing QBC-939 tumor BALB/c nude mice, when it treated with 5mg/kg dose of PS and laser light (650nm, 100J/cm 2 , 180mW/cm 2 ), the growth of tumor was inhibited compared to the control group. Among them, P3 exhibited better photodynamic antitumor efficacy on BALB/c nude mice at lower concentration. These results indicate that P3 is a new potential antitumor photosensitizer in photodynamic therapy and deserves further investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

Studies of porphyrin-containing specimens using an optical spectrometer connected to a confocal scanning laser microscope.

PubMed

Trepte, O; Rokahr, I; Andersson-Engels, S; Carlsson, K

1994-12-01

A spectrometer has been developed for use with a confocal scanning laser microscope. With this unit, spectral information from a single point or a user-defined region within the microscope specimen can be recorded. A glass prism is used to disperse the spectral components of the recorded light over a linear CCD photodiode array with 256 elements. A regulated cooling unit keeps the detector at 277 K, thereby allowing integration times of up to 60 s. The spectral resolving power, lambda/delta lambda, ranges from 350 at lambda = 400 nm to 100 at lambda = 700 nm. Since the entrance aperture of the spectrometer has the same size as the detector pinhole used during normal confocal scanning, the three-dimensional spatial resolution is equivalent to that of normal confocal scanning. Light from the specimen is deflected to the spectrometer by a solenoid controlled mirror, allowing fast and easy switching between normal confocal scanning and spectrometer readings. With this equipment, studies of rodent liver specimens containing porphyrins have been made. The subcellular localization is of interest for the mechanisms of photodynamic therapy (PDT) of malignant tumours. Spectroscopic detection is necessary to distinguish the porphyrin signal from other fluorescent components in the specimen. Two different substances were administered to the tissue, Photofrin, a haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), a precursor to protoporphyrin IX and haem in the haem cycle. Both are substances under clinical trials for PDT of malignant tumours. Following administration of these compounds to the tissue, the potent photosensitizer and fluorescent compound Photofrin, or protoporphyrin IX, respectively, is accumulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrinsically photosensitive retinal ganglion cells.

PubMed

Do, Michael Tri Hoang; Yau, King-Wai

2010-10-01

Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors.

Low-resistivity photon-transparent window attached to photo-sensitive silicon detector

DOEpatents

Holland, Stephen Edward

2000-02-15

The invention comprises a combination of a low resistivity, or electrically conducting, silicon layer that is transparent to long or short wavelength photons and is attached to the backside of a photon-sensitive layer of silicon, such as a silicon wafer or chip. The window is applied to photon sensitive silicon devices such as photodiodes, charge-coupled devices, active pixel sensors, low-energy x-ray sensors and other radiation detectors. The silicon window is applied to the back side of a photosensitive silicon wafer or chip so that photons can illuminate the device from the backside without interference from the circuit printed on the frontside. A voltage sufficient to fully deplete the high-resistivity photosensitive silicon volume of charge carriers is applied between the low-resistivity back window and the front, patterned, side of the device. This allows photon-induced charge created at the backside to reach the front side of the device and to be processed by any circuitry attached to the front side. Using the inventive combination, the photon sensitive silicon layer does not need to be thinned beyond standard fabrication methods in order to achieve full charge-depletion in the silicon volume. In one embodiment, the inventive backside window is applied to high resistivity silicon to allow backside illumination while maintaining charge isolation in CCD pixels.

Metal-based phthalocyanines as a potential photosensitizing agent in photodynamic therapy for the treatment of melanoma skin cancer

NASA Astrophysics Data System (ADS)

Maduray, Kaminee; Odhav, B.

2014-03-01

Photodynamic therapy (PDT) is an emerging medical treatment that uses photosensitizers (drug) which are activated by laser light for the generation of cytotoxic free radicals and singlet oxygen molecules that cause tumor cell death. In the recent years, there has been a focus on using and improving an industrial colorant termed phthalocyanines as a prospective photosensitizer because of its unique properties. This in vitro study investigated the photodynamic effect of indium (InPcCl) and iron (FePcCl) phthalocyanine chlorides on human skin cancer cells (melanoma). Experimentally, 2 x 104 cells/ml were seeded in 24-well tissue culture plates and allowed to attach overnight, after which cells were treated with different concentrations (2 μg/ml - 100 μg/ml) of InPcCl and FePcCl. After 2 h, cells were irradiated with constant light doses of 2.5 J/cm2, 4.5 J/cm2 and 8.5 J/cm2 delivered from a diode laser. Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT Assay. At 24 h after PDT, irradiation with a light dose of 2.5 J/cm2 for each photosensitizing concentration of InPcCl and FePcCl produced a significant decrease in cell viability, but when the treatment light dose was further increased to 4.5 J/cm2 and 8.5 J/cm2 the cell survival was less than 55% for photosensitizing concentrations of InPcCl and FePcCl from 4 μg/ml to 100 μg/ml. This PDT study concludes that low concentrations on InPcCl and FePcCl activated with low level light doses can be used for the effective in vitro killing of melanoma cancer cells.

Photosensitive function of encapsulated dye in carbon nanotubes.

PubMed

Yanagi, Kazuhiro; Iakoubovskii, Konstantin; Matsui, Hiroyuki; Matsuzaki, Hiroyuki; Okamoto, Hiroshi; Miyata, Yasumitsu; Maniwa, Yutaka; Kazaoui, Said; Minami, Nobutsugu; Kataura, Hiromichi

2007-04-25

Single-wall carbon nanotubes (SWCNTs) exhibit resonant absorption localized in specific spectral regions. To expand the light spectrum that can be utilized by SWCNTs, we have encapsulated squarylium dye into SWCNTs and clarified its microscopic structure and photosensitizing function. X-ray diffraction and polarization-resolved optical absorption measurements revealed that the encapsulated dye molecules are located at an off center position inside the tubes and aligned to the nanotube axis. Efficient energy transfer from the encapsulated dye to SWCNTs was clearly observed in the photoluminescence spectra. Enhancement of transient absorption saturation in the S1 state of the semiconducting SWCNTs was detected after the photoexcitation of the encapsulated dye, which indicates that ultrafast (<190 fs) energy transfer occurred from the dye to the SWCNTs.

Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of pig and rat after local administration

NASA Astrophysics Data System (ADS)

Bisson, Jean F.; Notter, Dominique; Labrude, P.; Vigneron, C.; Guillemin, Francois H.

1996-01-01

Photodynamic therapy (PDT) consists in the administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study was to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After studying the normal bladder histology of pig and rat, not much described so far, we studied the diffusion and localization of hematoporphyrin derivative (HpD) in vitro on the pig bladder and the biodistribution of HpD in vivo in the rat bladder, two and four hours after intravesical administration, by spectrofluorimetry and fluorescence microscopy. We have the following results: (1) no diffusion through the pig bladder wall was detected; (2) the penetration depth of HpD into the pig bladder wall was 450 plus or minus 44 micrometers (n equals 8), including urothelium and chorion in totality and a small part of the muscles; (3) the penetration depth of HpD into the rat bladder wall was 55 plus or minus 9 micrometer (n equals 9) after two hours and 960 plus or minus 118 micrometer (n equals 9) after four hours, corresponding respectively to the totality of the urothelium and a small part of the chorion or almost completely in the bladder wall, a small part of the adventicia being excluded. In conclusion, intravesical instillation is feasible and, as superficial bladder cancer, especially carcinoma in situ particularly occur in the urothelium or in the chorion, a bladder instillation of two hours should be advantageous.

In vitro study of bactericidal effect of low-level laser therapy in the presence of photosensitizer on cariogenic bacteria

NASA Astrophysics Data System (ADS)

Zanin, Iriana C. J.; Brugnera, Aldo, Jr.; Goncalves, Reginaldo B.

2002-06-01

The aim of this in vitro study was to determine whether low-level laser light in the presence of a photosensitizer could kill Streptococcus mutans and Streptococcus sobrinus. Suspensions of these microorganisms were exposed to a gallium-aluminium-arsenide laser light (660 nm) in the presence of photosensitizer toluidine blue O. Viable microorganisms were counted on brain heart agar plates after incubation at 37 degree(s)C in partial atmosphere of 10% CO2 for 48 hours. Their exposure to the laser light in the absence of the dye or the dye in the absence of the laser light presented no significant effect on the viability of the microorganisms. However, a decrease in the number of viable microorganisms was only verified when they were exposed to both the laser light and the dye at the same time. Their total growth inhibition was achieved with a dye concentration of 100 mg/mL and a light energy density of 28.8 J/cm2, after being exposed to laser light for 900 seconds. In conclusion, these results imply that these bacteria can be killed by low-power laser light in the presence of the photosensitizer.

Photosensitization of DNA damage by a new cationic pyropheophorbide derivative: sequence-specific formation of a frank scission.

PubMed

Kanony, Claire; Fabiano-Tixier, Anne-Sylvie; Ravanat, Jean-Luc; Vicendo, Patricia; Paillous, Nicole

2003-06-01

Pyropheophorbides are red-absorbing porphyrin-like photosensitizers that may interact with DNA either by intercalation or by external binding with self-stacking according to the value of the nucleotide to chromophore molar ratio (N/C). This article reports on the nature and sequence selectivity of the DNA damage photoinduced by a water-soluble chlorhydrate of aminopyropheophorbide. First, this pyropheophorbide is shown to induce on irradiation the cleavage of phiX174 DNA by both Type-I and -II mechanisms, suggested by scavengers and D2O effects. These conclusions are then improved by sequencing experiments performed on a 20-mer oligodeoxynucleotide (ODN) irradiated at wavelengths >345 nm in the presence of the dye, N/C varying from 2.5 to 0.5. Oxidation of all guanine residues to the same extent is observed after piperidine treatment on both single- and double-stranded ODN. Moreover, unexpectedly, a remarkable sequence-selective cleavage occurring at a 5'-CG-3' site is detected before alkali treatment. This frank break is clearly predominant for a low nucleotide to chromophore molar ratio, corresponding to a self-stacking of the dye along the DNA helix. The electrophoretic properties of the band suggest that this lesion results from a sugar oxidation, which leads via a base release to a ribonolactone residue. The proposal is supported by high-performance liquid chromatography-matrix-assisted laser desorption-ionization mass spectrometry experiments that also reveal other sequence-selective frank scissions of lower intensity at 5'-GC-3' or other 5'-CG-3' sites. This sequence selectivity is discussed with regard to the binding selectivity of cationic porphyrins.

Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol.

PubMed

Búzová, Diana; Kasák, Peter; Miškovský, Pavol; Jancura, Daniel

2013-06-01

Hypericin (Hyp) is a promising photosensitizer for photodiagnostic and photodynamic therapy of cancer. However, Hyp has a large conjugated system and in aqueous solutions forms insoluble aggregates which do not possess biological activity. This makes intravenous injection of Hyp problematic and restricts its medical applications. To overcome this problem, Hyp is incorporated into drug delivery systems which can increase its solubility and bioavailability. One of the possibilities is utilization of polymeric micelles. The most used hydrophilic block for preparation of polymeric micelles is polyethylen glycol (PEG). PEG is a polymer which for its lack of immunogenicity, antigenicity and toxicity obtained approval for use in human medicine. In this work we have studied the solubilization of Hyp aggregates in the presence of PEG-PE and PEG-cholesterol micelles. The concentration of polymeric micelles which allows total monomerization of Hyp corresponds to the critical micellar concentration of these micelles (~10(-6) M). We have also investigated the effect of the molecular weight and concentration of PEG on the transition of aggregated Hyp to its monomeric form. PEGs with low molecular weight (< 1000 g/mol) do not significantly contribute to the solubilization of Hyp. However, PEGs with molecular weight > 2000 g/mol efficiently transform Hyp aggregates to the monomeric state of this photosensitizer.

Intrinsic photosensitizer fluorescence measured using multi-diameter single-fiber spectroscopy in vivo

NASA Astrophysics Data System (ADS)

van Leeuwen-van Zaane, Floor; Gamm, Ute A.; van Driel, Pieter B. A. A.; Snoeks, Thomas J.; de Bruijn, Henriette S.; van der Ploeg-van den Heuvel, Angelique; Sterenborg, Henricus J. C. M.; Löwik, Clemens W.; Amelink, Arjen; Robinson, Dominic J.

2014-01-01

Quantification of fluorescence in vivo is complicated by the influence of tissue optical properties on the collected fluorescence signal. When tissue optical properties in the measurement volume are quantified, one can obtain the intrinsic fluorescence, which equals the product of fluorophore absorption coefficient and quantum yield. We applied this method to in vivo single-fiber fluorescence spectroscopy measurements on mouse tongue, skin, liver, and oral squamous cell carcinoma, where we detected intrinsic fluorescence spectra of the photosensitizers chlorin e6 and Bremachlorin at t=[3,4.5,6,24,48] h incubation time. We observed a tissue-dependent maximum of 35% variation in the total correction factor over the visible wavelength range. Significant differences in spectral shape over time between sensitizers were observed. Although the wavelength position of the fluorescence intensity maximum for ce6 shifted to the red, Bremachlorin showed a blue shift. Furthermore, the Bremachlorin peak appeared to be broader than the ce6 fluorescence peak. Intrinsic fluorescence intensity, which can be related to photosensitizer concentration, was decreasing for all time points but showed significantly more Bremachlorin present compared to ce6 at long incubation times. Results from this study can be used to define an optimal treatment protocol for Bremachlorin-based photodynamic therapy.

Photosensitizer-Loaded Branched Polyethylenimine-PEGylated Ceria Nanoparticles for Imaging-Guided Synchronous Photochemotherapy.

PubMed

Yang, Zhang-You; Li, Hong; Zeng, Yi-Ping; Hao, Yu-Hui; Liu, Cong; Liu, Jing; Wang, Wei-Dong; Li, Rong

2015-11-04

A multifunctional theranostic platform based on photosensitizer (chlorin e6, Ce6)-loaded branched polyethylenimine-PEGylated ceria nanoparticles (PPCNPs-Ce6) was created for the development of effective cancer treatments involving the use of imaging-guided synchronous photochemotherapy. PPCNPs-Ce6 with high Ce6 photosensitizer loading (Ce6: cerium ∼40 wt %) significantly enhanced the delivery of Ce6 into cells and its accumulation in lysosomes, remarkably improving photodynamic therapeutic (PDT) efficacy levels compared to those in the administration of free Ce6 at ultralow drug doses (∼200 nM). Interestingly, PPCNPs-Ce6 efficiently induced HeLa cell death even at low concentrations (∼10 μM) without the use of laser irradiation and exhibit chemocytotoxicity. Inductively coupled plasma mass spectrometry (ICP-MS) and biology transmission electron microscopy (Bio-TEM) analyses demonstrated that ceria nanoparticles enter cells abundantly and accumulate in lysosomes or large vesicles. We then evaluated the effects of the different materials on lysosomal integrity and function, which revealed that PPCNPs-Ce6 catastrophically impaired lysosomal function compared to results with PPCNPs and Ce6. Studies of apoptosis revealed greater induction of apoptosis by PPCNPs-Ce6 treatment. This multifunctional nanocarrier also exhibited a high degree of solubility and stability in aqueous solutions, suggesting its applicability for extensive biomedical application.

Photosensitizer conjugated iron oxide nanoparticles for simultaneous in vitro magneto-fluorescent imaging guided photodynamic therapy.

PubMed

Nafiujjaman, Md; Revuri, Vishnu; Nurunnabi, Md; Cho, Kwang Jae; Lee, Yong-Kyu

2015-04-04

In this study, photosensitizer conjugated iron oxide nanoparticles were strategically designed and prepared for simultaneous PDT and dual-mode fluorescence/MR imaging. The MRI contrast agent Fe3O4 was modified by APTES to functionalize the surface and further to link with heparin-pheophorbide-A conjugates.

Blazed vector gratings fabricated using photosensitive polymer liquid crystals and control of polarization diffraction

NASA Astrophysics Data System (ADS)

Ono, Hiroshi; Kuzuwata, Mitsuru; Sasaki, Tomoyuki; Noda, Kohei; Kawatsuki, Nobuhiro

2014-03-01

The blazed vector grating possessing antisymmetric distributions of the birefringence were fabricated by exposing the line-focused linearly polarized ultraviolet light on the photosensitive polymer liquid crystals. The polarization states of the diffraction beams can be highly and widely controlled by designing the blazed structures, and the diffraction properties were well-explained by Jones calculus.

Fungicidal response of a novel natural photosensitizer (Beta vulgaris) on Candida albicans with low-power laser radiation

NASA Astrophysics Data System (ADS)

Mittal, Subhangi; Roy, Sukhdev; Srivastava, J. N.

2013-05-01

We report the efficacy of an aqueous extract of Beta vulgaris as a novel, natural photosensitizer for use in photodynamic therapy against Candidiasis disease. This study evaluates the effect of different laser wavelengths (He-Ne: 633 nm, Nd-YAG: 532 nm), power (17, 27 mW) and duration of exposure (5, 10, 15 min) in combination with the Beta vulgaris natural photosensitizer on the viability of Candida albicans causing Candidiasis disease. Although inhibition was observed in all cases, a maximum of 51.91% inhibition takes place with the combination of Beta vulgaris exposed to 532 nm at 27 mW for 15 min by the Agar well diffusion method. The study is important in optimizing different parameters and designing a low-power, compact, non-invasive and portable device for treatment.

Optically Defined Multifunctional Patterning of Photosensitive Thin-Film Silica Mesophases

NASA Astrophysics Data System (ADS)

Doshi, Dhaval A.; Huesing, Nicola K.; Lu, Mengcheng; Fan, Hongyou; Lu, Yunfeng; Simmons-Potter, Kelly; Potter, B. G.; Hurd, Alan J.; Brinker, C. Jeffrey

2000-10-01

Photosensitive films incorporating molecular photoacid generators compartmentalized within a silica-surfactant mesophase were prepared by an evaporation-induced self-assembly process. Ultraviolet exposure promoted localized acid-catalyzed siloxane condensation, which can be used for selective etching of unexposed regions; for ``gray-scale'' patterning of refractive index, pore size, surface area, and wetting behavior; and for optically defining a mesophase transformation (from hexagonal to tetragonal) within the film. The ability to optically define and continuously control both structure and function on the macro- and mesoscales is of interest for sensor arrays, nanoreactors, photonic and fluidic devices, and low-dielectric-constant films.

Organic photosensitive cells having a reciprocal-carrier exciton blocking layer

DOEpatents

Rand, Barry P [Princeton, NJ; Forrest, Stephen R [Princeton, NJ; Thompson, Mark E [Anaheim Hills, CA

2007-06-12

A photosensitive cell includes an anode and a cathode; a donor-type organic material and an acceptor-type organic material forming a donor-acceptor junction connected between the anode and the cathode; and an exciton blocking layer connected between the acceptor-type organic material of the donor-acceptor junction and the cathode, the blocking layer consisting essentially of a material that has a hole mobility of at least 10.sup.-7 cm.sup.2/V-sec or higher, where a HOMO of the blocking layer is higher than or equal to a HOMO of the acceptor-type material.

Autonomous cycling between excitatory and inhibitory coupling in photosensitive chemical oscillators

NASA Astrophysics Data System (ADS)

Yengi, Desmond; Tinsley, Mark R.; Showalter, Kenneth

2018-04-01

Photochemically coupled Belousov-Zhabotinsky micro-oscillators are studied in experiments and simulations. The photosensitive oscillators exhibit excitatory or inhibitory coupling depending on the surrounding reaction mixture composition, which can be systematically varied. In-phase or out-of-phase synchronization is observed with predominantly excitatory or inhibitory coupling, respectively, and complex frequency cycling between excitatory and inhibitory coupling is found between these extremes. The dynamical behavior is characterized in terms of the corresponding phase response curves, and a map representation of the dynamics is presented.

Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX.

PubMed

Bellnier, David A; Greco, William R; Loewen, Gregory M; Nava, Hector; Oseroff, Allan R; Dougherty, Thomas J

2006-06-01

Photodynamic therapy (PDT) uses a photosensitizer activated by light, in an oxygen-rich environment, to destroy malignant tumors. Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the photosensitizers Photofrin, Photochlor, and 5-ALA-induced protoporphyrin IX (PpIX). In some studies the concentrations of photosensitizer in blood, and occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these individual studies were pooled and analyzed. This is the first published review to compare head-to-head the PK of Photofrin and Photochlor. Blood and tissue specimens were obtained from patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and PpIX were measured using fluorescence analysis. A non-linear mixed effects modeling approach was used to analyze the PK data for Photochlor (up to 4 days post-infusion; two-compartment model) and a simpler multipatient-data-pooling approach was used to model PK data for both Photofrin and Photochlor (at least 150 days post-infusion; three-compartment models). Physiological parameters were standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to facilitate comparisons between Photofrin and Photochlor. Serum concentration-time profiles obtained for Photofrin and Photochlor showed long circulating half-lives, where both sensitizers could be found more than 3 months after intravenous infusion; however, estimated plasma clearances (standard man) were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2 ml/hour). Volumes of distribution of the central compartment (standard man) for both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively) of plasma volume, implying that both photosensitizers are almost 100% bound to serum components. Circulating levels of PpIX were generally quite low, falling below the level of instrument sensitivity within a few days after topical application of 5-ALA. We have modeled the PK of

Photodynamic therapy of cancer with the photosensitizer PHOTOGEM

NASA Astrophysics Data System (ADS)

Sokolov, Victor V.; Chissov, Valery I.; Filonenko, E. V.; Sukhin, Garry M.; Yakubovskaya, Raisa I.; Belous, T. A.; Zharkova, Natalia N.; Kozlov, Dmitrij N.; Smirnov, V. V.

1995-01-01

The first clinical trials of photodynamic therapy (PDT) in Russia were started in P. A. Hertzen Moscow Research Oncology Institute in October of 1992. Up to now, 61 patients with primary or recurrent malignant tumors of the larynx (3), trachea (1), bronchus (11), nose (1), mouth (3), esophagus (12), vagina and uterine cervix (3), bladder (2), skin (6), and cutaneous and subcutaneous metastases of breast cancer and melanomas (6) have been treated by PDT with the photosensitizer Photogem. At least partial tumor response was observed in all of the cases, but complete remission indicating no evident tumors has been reached in 51% of the cases. Among 29 patients with early and first stage cancer 14 patients had multifocal tumors. Complete remission of tumors in this group reached 86%.

Silica Integrated Optical Circuits Based on Glass Photosensitivity

NASA Technical Reports Server (NTRS)

Abushagur, Mustafa A. G.

1999-01-01

Integrated optical circuits play a major rule in the new photonics technology both in communication and sensing due to their small size and compatibility with integrated circuits. Currently integrated optical circuits (IOCs) are fabricated using similar manufacturing to those used in the semiconductor industry. In this study we are considering a new technique to fabricate IOCs which does not require layers of photolithography, depositing and etching. This method is based on the photosensitivity of germanosilicate glasses. Waveguides and other IOC devises can be patterned in these glasses by exposing them using UV lasers. This exposure by UV light changes the index of refraction of the germanosilicate glass. This technique enjoys both the simplicity and flexibility of design and fabrication with also the potential of being fast and low cost.

Influence of aqueous media properties on aggregation and solubility of four structurally related meso-porphyrin photosensitizers evaluated by spectrophotometric measurements.

PubMed

Sobczyński, J; Tønnesen, H H; Kristensen, S

2013-02-01

Porphyrin photosensitizers tend to aggregate in aqueous solutions even in the micromolar concentration range. This is a challenge during formulation of e.g., parenteral preparations for photodynamic cancer therapy, or preparations for local or topical administration in antimicrobial photodynamic therapy. Monomerization is essential to achieve biocompatible drug formulations of high bioavailability and physiological response (i.e., photoreactivity) and low toxicity. The aggregation and solubilization of four structurally related meso-tetraphenyl porphyrin photosensitizers with nonionic (4-hydroxy), anionic (4-sulphonate; 4-carboxy) and cationic (4-trimethylanilinium) substituents were evaluated in various vehicles by use of UV-Vis spectroscopy. Substituents, overall charge and charge distribution influenced the pKa-values and interaction of the porphyrins with different solvents, excipients and impurities. Modification of medium polarity and solubilization by the nonionic surfactant Tween 80 adjusted the acid-base equilibria and increased the solubility by reduction of porphyrin aggregation. The selected porphyrins were sensitive towards ionic strength, temperature and inorganic impurities to various extents. The results will be further used during development of parenteral and topical formulations of porphyrin photosensitizers for use in photodynamic therapy of cancer and bacterial infections.

Cascading of molecular logic gates for advanced functions: a self-reporting, activatable photosensitizer.

PubMed

Erbas-Cakmak, Sundus; Akkaya, Engin U

2013-10-18

Logical progress: Independent molecular logic gates have been designed and characterized. Then, the individual molecular logic gates were coerced to work together within a micelle. Information relay between the two logic gates was achieved through the intermediacy of singlet oxygen. Working together, these concatenated logic gates result in a self-reporting and activatable photosensitizer. GSH=glutathione. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Singlet oxygen-based electrosensing by molecular photosensitizers

NASA Astrophysics Data System (ADS)

Trashin, Stanislav; Rahemi, Vanoushe; Ramji, Karpagavalli; Neven, Liselotte; Gorun, Sergiu M.; de Wael, Karolien

2017-07-01

Enzyme-based electrochemical biosensors are an inspiration for the development of (bio)analytical techniques. However, the instability and reproducibility of the reactivity of enzymes, combined with the need for chemical reagents for sensing remain challenges for the construction of useful devices. Here we present a sensing strategy inspired by the advantages of enzymes and photoelectrochemical sensing, namely the integration of aerobic photocatalysis and electrochemical analysis. The photosensitizer, a bioinspired perfluorinated Zn phthalocyanine, generates singlet-oxygen from air under visible light illumination and oxidizes analytes, yielding electrochemically-detectable products while resisting the oxidizing species it produces. Compared with enzymatic detection methods, the proposed strategy uses air instead of internally added reactive reagents, features intrinsic baseline correction via on/off light switching and shows C-F bonds-type enhanced stability. It also affords selectivity imparted by the catalytic process and nano-level detection, such as 20 nM amoxicillin in μl sample volumes.

Singlet oxygen-based electrosensing by molecular photosensitizers

PubMed Central

Trashin, Stanislav; Rahemi, Vanoushe; Ramji, Karpagavalli; Neven, Liselotte; Gorun, Sergiu M.; De Wael, Karolien

2017-01-01

Enzyme-based electrochemical biosensors are an inspiration for the development of (bio)analytical techniques. However, the instability and reproducibility of the reactivity of enzymes, combined with the need for chemical reagents for sensing remain challenges for the construction of useful devices. Here we present a sensing strategy inspired by the advantages of enzymes and photoelectrochemical sensing, namely the integration of aerobic photocatalysis and electrochemical analysis. The photosensitizer, a bioinspired perfluorinated Zn phthalocyanine, generates singlet-oxygen from air under visible light illumination and oxidizes analytes, yielding electrochemically-detectable products while resisting the oxidizing species it produces. Compared with enzymatic detection methods, the proposed strategy uses air instead of internally added reactive reagents, features intrinsic baseline correction via on/off light switching and shows C-F bonds-type enhanced stability. It also affords selectivity imparted by the catalytic process and nano-level detection, such as 20 nM amoxicillin in μl sample volumes.

A supramolecular photosensitizer system based on the host-guest complexation between water-soluble pillar[6]arene and methylene blue for durable photodynamic therapy.

PubMed

Yang, Kui; Wen, Jia; Chao, Shuang; Liu, Jing; Yang, Ke; Pei, Yuxin; Pei, Zhichao

2018-06-05

A supramolecular photosensitizer system WP6-MB was synthesized based on water-soluble pillar[6]arene and the photosensitizer methylene blue (MB) via host-guest interaction. MB can complex with WP6 directly with a high complex constant without further modification. In particular, WP6-MB can reduce the dark toxicity of MB remarkably. Furthermore, it can efficiently overcome photobleaching and extend the time for singlet oxygen production of MB upon light irradiation, which is significant for durable photodynamic therapy.

Multilayer photosensitive structures based on porous silicon and rare-earth-element compounds: Study of spectral characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirsanov, N. Yu.; Latukhina, N. V., E-mail: natalat@yandex.ru; Lizunkova, D. A.

2017-03-15

The spectral characteristics of the specular reflectance, photosensitivity, and photoluminescence (PL) of multilayer structures based on porous silicon with rare-earth-element (REE) ions are investigated. It is shown that the photosensitivity of these structures in the wavelength range of 0.4–1.0 μm is higher than in structures free of REEs. The structures with Er{sup 3+} ions exhibit a luminescence response at room temperature in the spectral range from 1.1 to 1.7 μm. The PL spectrum of the erbium impurity is characterized by a fine line structure, which is determined by the splitting of the {sup 4}I{sub 15/2} multiplet of the Er{sup 3+}more » ion. It is shown that the structures with a porous layer on the working surface have a much lower reflectance in the entire spectral range under study (0.2–1.0 μm).« less

Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy

PubMed Central

Denis, Tyler GSt; Hamblin, Michael R

2013-01-01

Photodynamic therapy (PDT) was discovered in 1900 by Raab, and has since emerged as a promising tool for treating diseases characterized by unwanted cells or hyperproliferating tissue (e.g., cancer or infectious disease). PDT consists of the light excitation of a photosensitizer (PS) in the presence of O2 to yield highly reactive oxygen species. In recent years, PDT has been improved by the synthesis of targeted bioconjugates between monoclonal antibodies and PS, and by investigating PS biodistribution and PD. Here, we provide a comprehensive review of major developments in PS-immunoconjugate-based PDT and the bioanalysis of these agents, with a specific emphasis on anticancer and antimicrobial PDT. PMID:23641699

Potential of systemic photosensitizers for PDT of skin malignancies

NASA Astrophysics Data System (ADS)

Philipp, Carsten M.; Müller, Ute; Urban, Peter; Berlien, H.-Peter

2008-04-01

Usually systemic photosensitizers (PS) require a long period of incubation (48-96h) after systemic admission. On the other hand clearing from healthy skin needs weeks or months. Severe side effects on skin are possible in case of uncontrolled light exposure. Topical PDT may solve this problem, but deep portions may not be sufficiently sensitized, resulting in a survival of some tumor cell population after PDT and recurrence. The same problem counts for actinic keratosis and Bowen's disease, but with even worse consequences as a resulting infiltrating growing squamous cell carcinoma (SCC) is likely to produce metastatic lesions. Light dosimetry is crucial also. Wavelenght, fluence and total energy may influence outcome of any PDT substantially. 17 patients with Bowen's disease or BCC where treated using a novel systemic PS (Fotolon ®) and 665nm light from a diode laser. Follow up time ranges between 2.5 and 1 years after treatment. 2 patients received a second PDT, in 15 patients one treatment was efficient. We found a remissions in 1, local control in 2 and no evidence of disease in 14 patients. Significant fluorescence was noted in all lesions. With a light protection protocol for only 48 hours no severe side effects where seen. One patient developed mild redness of sunlight exposed skin sites 24h after being discharged from light protection protocol. In comparison with currently available topical PS Fotolon ® offers some important advantages as secure photosenzitation of deep portions, single treatment, high selectivity combined with a high cure rate. In comparison with currently available systemic PS Fotolon ® offers short incubation time, high selectivity and short time of elimination, while efficiency was comparable to HPD (hematoporphyrin-derivate) PDT combined with ALA-5 PDT and without need for additional local PS-application for PDD.

A novel photosensitization treatment for the inactivation of fungal spores and cells mediated by curcumin.

PubMed

Al-Asmari, Fahad; Mereddy, Ram; Sultanbawa, Yasmina

2017-08-01

The global concerns regarding the emergence of fungicide-resistant strains and the impact of the excessive use of fungicidal practises on our health, food, and environment have increased, leading to a demand for alternative clean green technologies as treatments. Photosensitization is a treatment that utilises a photosensitiser, light and oxygen to cause cell damage to microorganisms. The effect of photosensitization mediated by curcumin on Aspergillus niger, Aspergillus flavus, Penicillium griseofulvum, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans and Zygosaccharomyces bailii was investigated using three methods. The viability of spores/cells suspended in aqueous buffer using different concentrations of curcumin solution (100-1000μM) and light dose (0, 24, 48, 72 and 96J/cm 2 ) were determined. Spraying curcumin solution on inoculated surfaces of agar plates followed by irradiation and soaking spores/cells in curcumin solution prior to irradiation was also investigated. In aqueous mixtures, photosensitised spores/cells of F. oxysporum and C. albicans were inhibited at all light doses and curcumin concentrations, while inactivation of A. niger, A. flavus P. griseofulvum, P. chrysogenum and Z. bailii were highly significant (P<0.001) reduced by 99%, 88.9%, 78%, 99.7% and 99.2% respectively. On the surface of agar plates, spores/cells exposed to a light dose of 360J/cm 2 sprayed with curcumin at 800μM showed complete inhibition for A. niger, F. oxysporum, C. albicans and Z. bailii, while A. flavus P. griseofulvum, and P. chrysogenum reduced by 75%, 80.4% and 88.5% respectively. Soaking spores/cells with curcumin solution prior to irradiation did not have a significant effect on the percentage reduction. These observations suggest that a novel photosensitization mediated curcumin treatment is effective against fungal spores/cells and the variation of percentage reduction was dependent on curcumin concentration, light dosage and fungal species

Self-assembly of Nano-rods in Photosensitive Phase Separation

NASA Astrophysics Data System (ADS)

Liu, Ya; Kuksenok, Olga; Maresov, Egor; Balazs, Anna

2012-02-01

Computer simulations reveal how photo-induced chemical reactions in polymeric mixtures can be exploited to create long-range order in materials whose features range from the sub-micron to the nanoscale. The process is initiated by shining a spatially uniform light on a photosensitive AB binary blend, which thereby undergoes both a reversible chemical reaction and phase separation. When a well-collimated, higher intensity light is rastered over the sample, the system forms defect-free, spatially periodic structures. We now build on this approach by introducing nanorods that have a preferential affinity for one the phases in a binary mixture. By rastering over the sample with the higher intensity light, we can create ordered arrays of rods within periodically ordered materials in essentially one processing step.

Multispectral confocal microscopy images and artificial neural nets to monitor the photosensitizer uptake and degradation in Candida albicans cells

NASA Astrophysics Data System (ADS)

Romano, Renan A.; Pratavieira, Sebastião.; da Silva, Ana P.; Kurachi, Cristina; Guimarães, Francisco E. G.

2017-07-01

This study clearly demonstrates that multispectral confocal microscopy images analyzed by artificial neural networks provides a powerful tool to real-time monitoring photosensitizer uptake, as well as photochemical transformations occurred.

Visible light-driven water oxidation promoted by host-guest interaction between photosensitizer and catalyst with a high quantum efficiency.

PubMed

Li, Hua; Li, Fei; Zhang, Biaobiao; Zhou, Xu; Yu, Fengshou; Sun, Licheng

2015-04-08

A highly active supramolecular system for visible light-driven water oxidation was developed with cyclodextrin-modified ruthenium complex as the photosensitizer, phenyl-modified ruthenium complexes as the catalysts, and sodium persulfate as the sacrificial electron acceptor. The catalysts were found to form 1:1 host-guest adducts with the photosensitizer. Stopped-flow measurement revealed the host-guest interaction is essential to facilitate the electron transfer from catalyst to sensitizer. As a result, a remarkable quantum efficiency of 84% was determined under visible light irradiation in neutral aqueous phosphate buffer. This value is nearly 1 order of magnitude higher than that of noninteraction system, indicating that the noncovalent incorporation of sensitizer and catalyst is an appealing approach for efficient conversion of solar energy into fuels.

A photosensitizer delivered by bispecific antibody redirected T lymphocytes enhances cytotoxicity against EpCAM-expressing carcinoma cells upon light irradiation.

PubMed

Blaudszun, André-René; Moldenhauer, Gerhard; Schneider, Marc; Philippi, Anja

2015-01-10

Recently conducted clinical trials have provided impressive evidence that chemotherapy resistant metastatic melanoma and several hematological malignancies can be cured using adoptive T cell therapy or T cell-recruiting bispecific antibodies. However, a significant fraction of patients did not benefit from these treatments. Here we have evaluated the feasibility of a novel combination therapy which aims to further enhance the killing potential of bispecific antibody-redirected T lymphocytes by using these cells as targeted delivery system for photosensitizing agents. For a first in vitro proof-of-concept study, ex vivo activated human donor T cells were loaded with a poly(styrene sulfonate) (PSS)-complex of the model photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP). In the absence of light and when loading with the water-soluble PSS/mTHPP-complex occurred at a tolerable concentration, viability and cytotoxic function of loaded T lymphocytes were not impaired. When "drug-enhanced" T cells were co-cultivated with EpCAM-expressing human carcinoma cells, mTHPP was transferred to target cells. Notably, in the presence of a bispecific antibody, which cross-links effector and target cells thereby inducing the cytolytic activity of cytotoxic T lymphocytes, significantly more photosensitizer was transferred. Consequently, upon irradiation of co-cultures, redirected drug-loaded T cells were more effective in killing A549 lung and SKOV-3 ovarian carcinoma cells than retargeted unloaded T lymphocytes. Particularly, the additive approach using redirected unloaded T cells in combination with appropriate amounts of separately applied PSS/mTHPP was less efficient as well. Thus, by loading T lymphocytes with a stimulus-sensitive anti-cancer drug, we were able to enhance the cytotoxic capacity of carrier cells. Photosensitizer boosted T cells could open new perspectives for adoptive T cell therapy as well as targeted photodynamic therapy. Copyright © 2014

On the factors influencing the performance of solar reactors for water disinfection with photosensitized singlet oxygen.

PubMed

Manjón, Francisco; Villén, Laura; García-Fresnadillo, David; Orellana, Guillermo

2008-01-01

Two solar reactors based on compound parabolic collectors (CPCs) were optimized for water disinfection by photosensitized singlet oxygen (1O2) production in the heterogeneous phase. Sensitizing materials containing Ru(II) complexes immobilized on porous silicone were produced, photochemically characterized, and successfully tested for the inactivation of up to 10(4) CFU mL(-1) of waterborne Escherichia coli (gram-negative) or Enterococcus faecalis (gram-positive) bacteria. The main factors determining the performance of the solar reactors are the type of photosensitizing material, the sensitizer loading, the CPC collector geometry (fin- vs coaxial-type), the fluid rheology, and the balance between concurrent photothermal--photolytic and 1O2 effects on the microorganisms' inactivation. In this way, at the 40 degrees N latitude of Spain, water can be disinfected on a sunny day (0.6-0.8 MJ m(-2) L(-1) accumulated solar radiation dose in the 360-700 nm range, typically 5-6 h of sunlight) with a fin-type reactor containing 0.6 m2 of photosensitizing material saturated with tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) (ca. 2.0 g m(-2)). The optimum rheological conditions require laminar-to-transitional water flow in both prototypes. The fin-type system showed better inactivation efficiency than the coaxial reactor due to a more important photolytic contribution. The durability of the sensitizing materials was tested and the operational lifetime of the photocatalyst is at least three months without any reduction in the bacteria inactivation efficiency. Solar water disinfection with 1O2-generating films is demonstrated to be an effective technique for use in isolated regions of developing countries with high yearly average sunshine.

Molecular design of light-harvesting photosensitizers: effect of varied linker conjugation on interfacial electron transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Jianbing; Swierk, John R.; Hedstrom, Svante

2016-06-30

Here, interfacial electron transfer dynamics of a series of photosensitizers bound to TiO 2 via linkers of varying conjugation strength are explored by spectroscopic and computational techniques. Injection and recombination depend on the extent of conjugation in the linker, where the LUMO delocalization determines the injection dynamics but both the HOMO and HOMO–1 are involved in recombination.

Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers

NASA Astrophysics Data System (ADS)

Chissov, Valery I.; Sokolov, Victor V.; Trakhtenberg, A. K.; Mamontov, A. S.; Vaschakmadze, L. A.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Belous, T. A.; Gladunov, V. K.; Aristarkhova, E. I.; Zharkova, Natalia N.; Menenkov, V. D.

1996-01-01

The paper presents the results of photodynamic therapy (PDT) of early-stage cancer of lung (17 patients), esophagus (8 patients) and stomach (10 patients). Fifteen patients had second primary tumors. New drugs photoheme and photosens were used as photosensitizers. Complete remission was obtained in 87%. The patients are followed up without relapses to 2.5 years.

Effect of dye localization and self-interactions on the photosensitized generation of singlet oxygen by rose bengal bound to bovine serum albumin.

PubMed

Turbay, María Beatriz Espeche; Rey, Valentina; Argañaraz, Natalia M; Morán Vieyra, Faustino E; Aspée, Alexis; Lissi, Eduardo A; Borsarelli, Claudio D

2014-12-01

The spectroscopic and photophysical properties of rose bengal (RB) encased in bovine serum albumin (BSA) have been examined to evaluate the photosensitized generation of singlet molecular oxygen ((1)O2). The results show that RB photophysical and photosensitizing properties are highly modulated by the average number of dye molecules per protein (n). At n ≪ 1, the dye molecule is tightly located into the hydrophobic nanocavity site I of the BSA molecule with a binding constant Kb = 0.15 ± 0.01 μM(-1). The interaction with surrounding amino acids induces heterogeneous decay of both singlet and triplet excited states of RB and partially reduce its triplet quantum yield as compared with that in buffer solution. However, despite of the diffusive barrier imposed by the protein nanocavity to (3)O2, the quenching of (3)RB(∗):BSA generates (1)O2 with quantum yield ΦΔ = 0.35 ± 0.05. In turns, the intraprotein generated (1)O2 is able to diffuse through the bulk solution, where is dynamically quenched by BSA itself with an overall quenching rate constant of 7.3 × 10(8) M(-1) s(-1). However, at n>1, nonspecific binding of up to ≈ 6RB molecules per BSA is produced, allowing efficient static quenching of excited states of RB preventing photosensitization of (1)O2. These results provide useful information for development of dye-protein adducts suitable for using as potential intracellular photosensitizers. Copyright © 2014 Elsevier B.V. All rights reserved.

A TiO₂ nanoparticle system for sacrificial solar H₂ production prepared by rational combination of a hydrogenase with a ruthenium photosensitizer.

PubMed

Reisner, Erwin; Armstrong, Fraser A

2011-01-01

A hybrid system comprising a hydrogenase and a photosensitizer co-attached to a nanoparticle serves as a rational model for fast dihydrogen (H(2)) production using visible light. This chapter describes a stepwise procedure for preparing TiO(2) nanoparticles functionalized with a hydrogenase from Desulfomicrobium baculatum (Db [NiFeSe]-H) and a tris(bipyridyl)ruthenium photosensitizer (RuP). Upon irradiation with visible light, these particles produce H(2) from neutral water at room temperature in the presence of a sacrificial electron donor - a test-system for the cathodic half reaction of water splitting. In particular, we describe how a hydrogenase and a photosensitizer with desired properties, including strong adsorption on TiO(2), can be selected by electrochemical methods. The catalyst Db [NiFeSe]-H is selected for its high H(2) production activity even when H(2) and traces of O(2) are present. Adsorption of Db [NiFeSe]-H and RuP on TiO(2) electrodes results in high electrochemical and photocatalytic activities that translate into nanoparticles exhibiting efficient light harvesting, charge separation, and sacrificial H(2) generation.

Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery.

PubMed

Li, Juanjuan; Meng, Xuan; Deng, Jian; Lu, Di; Zhang, Xin; Chen, Yanrui; Zhu, Jundong; Fan, Aiping; Ding, Dan; Kong, Deling; Wang, Zheng; Zhao, Yanjun

2018-05-23

Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT's antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.

Drug Discovery of Antimicrobial Photosensitizers Using Animal Models

PubMed Central

Sharma, Sulbha K.; Dai, Tianhong; Kharkwal, Gitika B.; Huang, Ying-Ying; Huang, Liyi; Bil De Arce, Vida J.; Tegos, George P.; Hamblin, Michael R.

2012-01-01

Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form a long-lived triplet state that can interact with molecular oxygen to produce reactive oxygen species such as singlet oxygen and hydroxyl radical that kill the microbial cells. To obtain effective PS for treatment of infections it is necessary to use cationic PS with positive charges that are able to bind to and penetrate different classes of microbial cells. Other drug design criteria require PS with high absorption coefficients in the red/near infra-red regions of the spectrum where light penetration into tissue is maximum, high photostability to minimize photobleaching, and devising compounds that will selectively bind to microbial cells rather than host mammalian cells. Several molecular classes fulfill many of these requirements including phenothiazinium dyes, cationic tetrapyrroles such as porphyrins, phthalocyanines and bacteriochlorins, cationic fullerenes and cationic derivatives of other known PS. Larger structures such as conjugates between PS and cationic polymers, cationic nanoparticles and cationic liposomes that contain PS are also effective. In order to demonstrate in vivo efficacy it is necessary to use animal models of localized infections in which both PS and light can be effectively delivered into the infected area. This review will cover a range of mouse models we have developed using bioluminescent pathogens and a sensitive low light imaging system to non-invasively monitor the progress of the infection in real time. Effective aPDT has been demonstrated in acute lethal infections and chronic biofilm infections; in infections caused by Gram-positive, Gram-negative bacteria and fungi; in infections in wounds, third degree burns

ProTEK PSB as Biotechnology Photosensitive Protection Mask on 3C-SiC-on-Si in MEMS Sensor

NASA Astrophysics Data System (ADS)

Marsi, N.; Majlis, B. Y.; Mohd-Yasin, F.; Hamzah, A. A.; Mohd Rus, A. Z.

2016-11-01

This project presents the fabrication of MEMS employing a cubic silicon carbide (3C- SiC) on silicon wafer using newly developed ProTEK PSB as biotechnology photosensitive protection mask. This new biotechnology can reduce the number of processes and simplify the process flow with minimal impact on overall undercut performance. The 680 pm thick wafer is back-etched, leaving the 3C-SiC thin film with a thickness of 1.0 μm as the flexible diaphragm to detect pressure. The effect of the new coating of ProTEK PSB on different KOH solvents were investigated depending on various factors such as development time, final cure temperature and the thickness of the ProTEK PSB deposited layer. It is found that 6.174 μm thickness of ProTEK PSB offers some possibility of reducing the processing time compared to silicon nitride etch masks in KOH (55%wt, 80°C). The new ProTEK PSB biotechnology photosensitive protection mask indicates good stability and sustains its performance in different treatments under KOH and IPA for 8 hours. This work also revealed that the fabrication of MEMS sensors using the new biotechnology photosensitive protection mask provides a simple assembly approach and reduces manufacturing costs. The MEMS sensor can operate up to 500 °C as indicated under the sensitivity of 0.826 pF/MPa with nonlinearity and hysteresis of 0.61% and 3.13%, respectively.

Formulation of benzoporphyrin derivatives in Pluronics.

PubMed

Chowdhary, Rubinah K; Chansarkar, Namrata; Sharif, Isha; Hioka, Noboru; Dolphin, David

2003-03-01

This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents.

Liquid crystal nanoparticles for delivery of photosensitizers for photodynamic therapy

NASA Astrophysics Data System (ADS)

Nag, Okhil K.; Naciri, Jawad; Delehanty, James B.

2018-02-01

The main principle of photodynamic therapy (PDT) is to kill malignant cells by generation of reactive oxygen species (ROS). PDT appeared highly effective when ROS can be produced in subcellular location such as plasma membrane. The plasma membrane maintains the structural integrity of the cell and regulates multiple important cellular processes, such as endocytosis, trafficking, and apoptotic pathways, could be one of the best points to kill the cancer cells. Previously, we have developed a plasma membrane-targeted liquid crystal nanoparticle (LCNP) formulation that can be loaded with dyes or drugs. Here we highlight the utility of this LCNP for membrane targeted delivery and imaging for a photosensitizer (PS) for PDT applications.

Aluminum–phthalocyanine chloride associated to poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as a new third-generation photosensitizer for anticancer photodynamic therapy

PubMed Central

Muehlmann, Luis Alexandre; Ma, Beatriz Chiyin; Longo, João Paulo Figueiró; Almeida Santos, Maria de Fátima Menezes; Azevedo, Ricardo Bentes

2014-01-01

Photodynamic therapy is generally considered to be safer than conventional anticancer therapies, and it is effective against different kinds of cancer. However, its clinical application has been significantly limited by the hydrophobicity of photosensitizers. In this work, a system composed of the hydrophobic photosensitizer aluminum–phthalocyanine chloride (AlPc) associated with water dispersible poly(methyl vinyl ether-co-maleic anhydride) nanoparticles is described. AlPc was associated with nanoparticles produced by a method of solvent displacement. This system was analyzed for its physicochemical characteristics, and for its photodynamic activity in vitro in cancerous (murine mammary carcinoma cell lineage 4T1, and human mammary adenocarcinoma cells MCF-7) and noncancerous (murine fibroblast cell lineage NIH/3T3, and human mammary epithelial cell lineage MCF-10A) cell lines. Cell viability and the elicited mechanisms of cell death were evaluated after the application of photodynamic therapy. This system showed improved photophysical and photochemical properties in aqueous media in comparison to the free photosensitizer, and it was effective against cancerous cells in vitro. PMID:24634582

Novel porphyrin conjugates with a potent photodynamic antitumor effect: differential efficacy of mono- and bis-beta-cyclodextrin derivatives in vitro and in vivo.

PubMed

Kralova, Jarmila; Synytsya, Alla; Pouckova, Pavla; Koc, Michal; Dvorak, Michal; Kral, Vladimir

2006-01-01

In the present study we investigated the photosensitizing properties of two novel mono- and bis-cyclodextrin tetrakis (pentafluorophenyl) porphyrin derivatives in several tumor cell lines and in BALB/c mice bearing subcutaneously transplanted syngeneic mouse mammary carcinoma 4T1. Both studied sensitizers were localized mainly in lysosomes and were found to induce cell death by triggering apoptosis in human leukemic cells HL-60. In 4T1 and other cell lines both apoptotic and necrotic modes of cell death occurred depending on drug and light doses. Mono-cyclodextrin porphyrin derivative P(beta-CD)1 exhibited stronger in vitro phototoxic effect than bis-cyclodextrin derivative P(beta-CD)2. However, in vivo P(beta-CD)2 displayed faster tumor uptake with maximal accumulation 6 h after application, leading to complete and prolonged elimination of subcutaneous tumors within 3 days after irradiation (100 J cm(-2)). In contrast, P(beta-CD)1 uptake was slower (48 h) and the reduction of tumor mass was only transient, reaching the maximum at the 12 h interval when a favorable tumor-to-skin ratio appeared. Thus, P(beta-CD)2 represents a new photosensitizing drug displaying fast and selective tumor uptake, strong antitumor activity and fast elimination from the body.

Spectral properties of singlet-oxygen luminescence in the IR Region at the 1Δ g → 3Σ g transition in the presence of fullerene as a photosensitizer

NASA Astrophysics Data System (ADS)

Kiselev, V. M.; Bagrov, I. V.

2017-10-01

The spectral properties of singlet-oxygen luminescence at the 1Δ g → 3Σ g transition observed using fullerene as a photosensitizer are analyzed. It is shown that the use of C60 and C70 fullerenes for singlet-oxygen generation exhibits all the main spectral regularities observed for other photosensitizers. The results of investigations in this field are summarized.

Bax Translocation Mediated Mitochondrial Apoptosis and Caspase Dependent Photosensitizing Effect of Ficus religiosa on Cancer Cells

PubMed Central

Thankayyan R, Santhosh Kumar; Sithul, Hima; Sreeharshan, Sreeja

2012-01-01

The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE) in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide) double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9). Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS) by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and partial Caspase

Efficacy of gallium phthalocyanine as a photosensitizing agent in photodynamic therapy for the treatment of cancer

NASA Astrophysics Data System (ADS)

Maduray, Kaminee; Odhav, Bharti

2012-12-01

Photodynamic therapy is a revolutionary treatment aimed at treating cancers without surgery or chemotherapy. It is based on the discovery that certain chemicals known as photosensitizing agents (e.g. porphyrins, phthalocyanines, etc.) can kill cancerous cells when exposed to low level laser light at a specific wavelength. The present study investigates the cellular uptake and photodynamic effect of gallium (III) phthalocyanine chloride (GaPcCl) on Caco-2 cancer cells. Caco-2 cells were treated with different concentrations of GaPcCl for 2 h before treatment with a diode laser (λ = 661 nm, laser power = 90 mW) delivering a light dose of 2.5 J/cm2, 4.5 J/cm2 or 8.5 J/cm2. After 24 h, the cell viability of post-irradiated cells was measured using the MTT assay. Cellular uptake studies were performed by photosensitizing cells with GaPcCl for 30 min, 2 h, 10 h, 12 h, 18 h and 24 h before lysing the treated cells into solution to measure the GaPcCl fluorescence emission at an excitation wavelength of 600 nm. Results showed an increase in fluorescence intensity of emission peaks at longer incubation times, indicating a greater cellular uptake of GaPcCl by Caco-2 cells at 24 h in comparison to 30 min. GaPcCl at a concentration of 100 μg/ml activated with a laser light dose of 8.5 J/cm2 reduced the cell viability of Caco-2 cells to 27%. This concludes that GaPcCl activated with low level laser light can be used as a photosensitizing agent for the in vitro PDT treatment of colon cancer.

Glutathione-capped gold nanoclusters as photosensitizers. Visible light-induced hydrogen generation in neutral water.

PubMed

Chen, Yong-Siou; Kamat, Prashant V

2014-04-23

Glutathione-capped metal nanoclusters (Aux-GSH NCs) which exhibit molecular-like properties are employed as a photosensitizer for hydrogen generation in a photoelectrochemical cell (PEC) and a photocatalytic slurry reactor. The reversible reduction (E(0) = -0.63 V vs RHE) and oxidation (E(0) = 0.97 and 1.51 V vs RHE) potentials of these metal nanoclusters make them suitable for driving the water-splitting reaction. When a mesoscopic TiO2 film sensitized by Aux-GSH NCs is used as the photoanode with a Pt counter electrode in aqueous buffer solution (pH = 7), we observe significant photocurrent activity under visible light (400-500 nm) excitation. Additionally, sensitizing Pt/TiO2 nanoparticles with Aux-GSH NCs in an aqueous slurry system and irradiating with visible light produce H2 at a rate of 0.3 mmol of hydrogen/h/g of Aux-GSH NCs. The rate of H2 evolution is significantly enhanced (∼5 times) when a sacrificial donor, such as EDTA, is introduced into the system. Using metal nanoclusters as a photosensitizer for hydrogen generation lays the foundation for the future exploration of other metal nanoclusters with well-controlled numbers of metal atoms and capping ligands.

Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans

PubMed Central

Asadi, Shahrzad; Sismanopoulos, Nikolaos; Butcher, Alan; Fu, Xueyan; Katsarou-Katsari, Alexandra; Antoniou, Christina; Theoharides, Theoharis C.

2012-01-01

Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell “stabilizer”, is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD2. Que and cromolyn also inhibit histamine, leukotrienes and PGD2 from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption. PMID:22470478

New photosensitizers for photodynamic therapy

PubMed Central

Abrahamse, Heidi; Hamblin, Michael R.

2016-01-01

Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. PMID:26862179

New photosensitizers for photodynamic therapy.

PubMed

Abrahamse, Heidi; Hamblin, Michael R

2016-02-15

Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. © 2016 Authors; published by Portland Press Limited.

A Dual Anticancer Efficacy Molecule: A Selective Dark Cytotoxicity Photosensitizer.

PubMed

Chen, Jyun-Wei; Chang, Cheng-Chung

2016-11-09

Unlike traditional binary nanostructures that construct chemotherapy drugs and photodynamic therapy photosensitizers, we introduce a molecule with a chemo-photodynamic dual therapy function. A water-soluble aggregation-induced emission enhancement (AIEE) fluorogen, NV-12P, was designed and synthesized based on asymmetric 1,6-disubstituted naphthalene and can generate particular reactive oxygen species to undergo type I photodynamic therapy under irradiation. Furthermore, this compound can specifically localize in mitochondria and, after biological evaluation, can cause mitochondrial dysfunction and potent cytotoxicity to cancer cells but not normal cells. We conclude that this compound is a potential dual-toxic efficacy molecule because it exhibits selective dark cytotoxicity and efficient photodamage in cancer cells. Additionally, we also supported the optimal combinational treatment course for the best chemo-phototherapy efficacy.

Photosensitivity of p-type black Si field emitter arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mingels, S., E-mail: smingels@uni-wuppertal.de; Porshyn, V.; Lützenkirchen-Hecht, D.

We have investigated the properties of black Si field emitter arrays under strong electric fields and laser illumination. A low onset field of 1.8 MV/m for an emission current of 1 nA was obtained. A pronounced saturation region of the dark and photo-enhanced current was observed, which provided a short-term stability of 0.1% at 0.4 μA and 0.7% at 1.0 μA, respectively. As maximum value for the photosensitivity, an on-off current switching ratio of 43 reaching about 13 μA was achieved at a laser power of 15 mW. Electron spectra in the dark and under laser illumination are presented, showing a current and light-sensitivemore » voltage drop across the emitters as well as hints for hot electron emission.« less

Versatile Polymer Nanoparticles as Two-Photon-Triggered Photosensitizers for Simultaneous Cellular, Deep-Tissue Imaging, and Photodynamic Therapy.

PubMed

Guo, Liang; Ge, Jiechao; Liu, Qian; Jia, Qingyan; Zhang, Hongyan; Liu, Weimin; Niu, Guangle; Liu, Sha; Gong, Jianru; Hackbarth, Steffen; Wang, Pengfei

2017-06-01

Clinical applications of current photodynamic therapy (PDT) photosensitizers (PSs) are often limited by their absorption in the UV-vis range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep-seated tumors. Alternatively, two-photon excited PS (TPE-PS) using NIR light triggered is one the most promising candidates for PDT improvement. Herein, multimodal polymer nanoparticles (PNPs) from polythiophene derivative as two-photon fluorescence imaging as well as two-photon-excited PDT agent are developed. The prepared PNPs exhibit excellent water dispersibility, high photostability and pH stability, strong fluorescence brightness, and low dark toxicity. More importantly, the PNPs also possess other outstanding features including: (1) the high 1 O 2 quantum yield; (2) the strong two-photon-induced fluorescence and efficient 1 O 2 generation; (3) the specific accumulation in lysosomes of HeLa cells; and (4) the imaging detection depth up to 2100 µm in the mock tissue under two-photon. The multifunctional PNPs are promising candidates as TPE-PDT agent for simultaneous cellular, deep-tissue imaging, and highly efficient in vivo PDT of cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radical production from photosensitization of imidazoles, benzophenone and 4-benzoylbenzoic acid

NASA Astrophysics Data System (ADS)

Corral Arroyo, Pablo; González, Laura; Steimer, Sarah; Volkamer, Rainer; George, Christian; Bartels-Rausch, Thorsten; Ammann, Markus

2016-04-01

Reactions promoted by light are key in atmospheric chemistry. Some of them occur in the condensed phase of aerosols which may contain light absorbing organic compounds that provoke photochemical reactions such as humic like material (GEORGE 2005). Our aim is to understand the role these reactions play in atmospheric photochemistry. This work explores the radical reactions initiated by UV light in mixtures of citric acid (CA) and imidazole-2-carboxaldehyde (IC), benzophenone and 4-Benzoylbenzoic acid (BBA) using NO as a probe molecule for HO2, by means of coated wall flow tube experiments. The loss of NO was measured by a chemiluminescence detector (CLD), also configured for the distinction of the products (HONO or NO2). The dependence of the NO loss on the initial NO concentration, the photosensitizer concentration in the film, relative humidity, light intensity, oxygen molar fraction were investigated as well as the HONO and NO2 yields. We found a clear correlation between the loss of NO above the film and the molar ratio of photosensitizer/CA, and also between the NO loss and the light intensity. The variation of the observed NO loss with oxygen corroborates a mechanism, in which the triplet excited state of the photosensitizer is reduced likely by the predominant donor in the system, citric acid, to a reduced ketyl radical. This reactive species is transferring an electron to molecular oxygen, which in turn leads to production of HO2 radicals, which are released to the gas phase. Therefore, in absence of gas phase oxidants, the loss of NO in the gas phase could be related to the production of HO2 radicals in the condensed phase. Relative humidity had a strong impact on the HO2 output, which shows a maximum value at intermediate humidity around 30%, likely due to different competing effects of dilution and reactant mobility. The observed NO2/HONO ratio was around 1.4 consistent with the secondary chemistry of HO2 in presence of NO in the gas phase, indicating no

Solid-phase fullerene-like nanostructures as singlet oxygen photosensitizers in liquid media

NASA Astrophysics Data System (ADS)

Belousova, I. M.; Danilov, O. B.; Kiselev, V. M.; Kislyakov, I. M.; Kris'ko, T. K.; Murav'eva, T. D.; Videnichev, D. A.

2007-04-01

Singlet oxygen generation by fullerene and astralen containing surfaces and powders under visible irradiation was studied in water and organic liquids by means of 1Δ g state luminescence and chemical scavenger transmittance measurements. The chemical method, pioneered for solid photosensitizers of 10 II, allowed to measure the singlet oxygen concentration in the aqueous medium down to 10 8 cm -3. The singlet oxygen sensitizing by the solid-phase fullerene-containing systems was found to be 100 times less effective then by fullerene in solution. The results obtained confirm the applicability of these structures in biology and medicine.

Improvement in device performance from a mixture of a liquid crystal and photosensitive acrylic prepolymer with the photoinduced vertical alignment method

PubMed Central

Ho, Czung-Yu; Lin, Fa-Hsin; Tao, Yu-Tai; Lee, Jiunn-Yih

2011-01-01

In a multicomponent nematic liquid crystal (NLC) mixture of a liquid crystal (negative-type NLC) and a photosensitive acrylic prepolymer, photopolymerization upon UV irradiation induces the separation of the LC and photosensitive acrylic prepolymer layers, thereby leading to a vertical arrangement of LC molecules. In this study, we propose a simple vertical alignment method for LC molecules, by adding a chiral smectic A (SmA∗) liquid crystal having homeotropic texture characteristics to an NLC mixture solution. Measurements of electro-optical properties revealed that the addition of the SmA∗ LC not only strengthened the anchoring force of the copolymer alignment film surface, but also significantly enhanced the contrast ratio (∼73%), response time and grayscale switching performance of the device. PMID:27877462

A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light.

PubMed

Turan, Ilke Simsek; Yildiz, Deniz; Turksoy, Abdurrahman; Gunaydin, Gurcan; Akkaya, Engin U

2016-02-18

The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Benzoporphyrin derivative and light-emitting diode for use in photodynamic therapy: Applications of space light-emitting diode technology

NASA Astrophysics Data System (ADS)

Whelan, Harry T.; Houle, John M.; Bajic, Dawn M.; Schmidt, Meic H.; Reichert, Kenneth W.; Meyer, Glenn A.

1998-01-01

Photodynamic therapy (PDT) is a cancer treatment modality that recently has been applied as adjuvant therapy for brain tumors. PDT consists of intravenously injecting a photosensitizer, which preferentially accumulates in tumor cells, into a patient and then activating the photosensitizer with a light source. This results in free radical generation followed by cell death. The development of more effective light sources for PDT of brain tumors has been facilitated by applications of space light-emitting diode array technology; thus permitting deeper tumor penetration of light and use of better photosensitizers. Currently, the most commonly used photosensitizer for brain tumor PDT is Photofrin®. Photofrin® is a heterogeneous mixture of compounds derived from hematoporphyrin. Photofrin® is activated with a 630 nm laser light and does destroy tumor cells in animal models and humans. However, treatment failure does occur using this method. Most investigators attribute this failure to the limited penetration of brain tissue by a 630 nm laser light and to the fact that Photofrin® has only a minor absorption peak at 630 nm, meaning that only a small fraction of the chemical is activated. Benzoporphyrin Derivative Monoacid Ring A (BPD) is a new, second generation photosensitizer that can potentially improve PDT for brain tumors. BPD has a major absorption peak at 690 nm, which gives it two distinct advantages over Photofrin®. First, longer wavelengths of light penetrate brain tissue more easily so that larger tumors could be treated, and second, the major absorption peak means that a larger fraction of the drug is activated upon exposure to light. In the first part of this project we have studied the tumoricidal effects of BPD in vitro using 2A9 canine glioma and U373 human glioblastoma cell cultures. Using light emitting diodes (LED) with a peak emission of 688 nm as a light source, cell kill of up to 86 percent was measured in these cell lines by tumor DNA synthesis

Challenge toward breakage of RLS trade-off for EUV lithography by Photosensitized Chemically Amplified Resist (PSCAR) with flood exposure

NASA Astrophysics Data System (ADS)

Nagahara, Seiji; Carcasi, Michael; Nakagawa, Hisashi; Buitrago, Elizabeth; Yildirim, Oktay; Shiraishi, Gosuke; Terashita, Yuichi; Minekawa, Yukie; Yoshihara, Kosuke; Tomono, Masaru; Mizoguchi, Hironori; Estrella, Joel; Nagai, Tomoki; Naruoka, Takehiko; Dei, Satoshi; Hori, Masafumi; Oshima, Akihiro; Vockenhuber, Michaela; Ekinci, Yasin; Meeuwissen, Marieke; Verspaget, Coen; Hoefnagels, Rik; Rispens, Gijsbert; Maas, Raymond; Nakashima, Hideo; Tagawa, Seiichi

2016-03-01

This paper proposes a promising approach to break the resolution (R), line-edge-roughness (LER), and sensitivity (S) trade-off (RLS trade-off) relationships that limit the ultimate lithographic performance of standard chemically amplified resists (CAR). This is accomplished in a process that uses a Photosensitized Chemically Amplified Resist (PSCAR) in combination with a flood-exposure in an in-line track connected to a pattern exposure tool. PSCAR is a modified CAR which contains a photosensitizer precursor (PP) in addition to other standard CAR components such as a protected polymer, a photo acid generator (PAG) and a quencher. In this paper, the PSCAR concept and the required conditions in resist formulation are carefully explained. In the PSCAR process, the sensitivity improvement is accomplished by PAG decomposition to selectively generate more acid at the pattern exposed areas during the flood exposure. The selective photosensitization happens through the excitation of the photosensitizer (PS) generated by the deprotection of the PP at the pattern exposed areas. A higher resist chemical gradient which leads to an improved resolution and lower LER values is also predicted using the PSCAR simulator. In the PSCAR process, the improved chemical gradient can be realized by dual acid quenching steps with the help of increased quencher concentration. Acid quenching first happens simultaneously with acid catalytic PP to PS reactions. As a result, a sharpened PS latent image is created in the PSCAR. This image is subsequently excited by the flood exposure creating additional acid products at the pattern exposed areas only. Much the same as in the standard CAR system, unnecessary acid present in the non-pattern exposed areas can be neutralized by the remaining quencher to therefore produce sharper acid latent images. EUV exposure results down to 15 nm half pitch (HP) line/space (L/S) patterns using a PSCAR resist indicate that the use of PSCAR has the potential to

Bodipy-C60 triple hydrogen bonding assemblies as heavy atom-free triplet photosensitizers: preparation and study of the singlet/triplet energy transfer.

PubMed

Guo, Song; Xu, Liang; Xu, Kejing; Zhao, Jianzhang; Küçüköz, Betül; Karatay, Ahmet; Yaglioglu, Halime Gul; Hayvali, Mustafa; Elmali, Ayhan

2015-07-01

Supramolecular triplet photosensitizers based on hydrogen bonding-mediated molecular assemblies were prepared. Three thymine-containing visible light-harvesting Bodipy derivatives ( B-1 , B-2 and B-3 , which show absorption at 505 nm, 630 nm and 593 nm, respectively) were used as H-bonding modules, and 1,6-diaminopyridine-appended C 60 was used as the complementary hydrogen bonding module ( C-1 ), in which the C 60 part acts as a spin converter for triplet formation. Visible light-harvesting antennae with methylated thymine were prepared as references ( B-1-Me , B-2-Me and B-3-Me ), which are unable to form strong H-bonds with C-1 . Triple H-bonds are formed between each Bodipy antenna ( B-1 , B-2 and B-3 ) and the C 60 module ( C-1 ). The photophysical properties of the H-bonding assemblies and the reference non-hydrogen bond-forming mixtures were studied using steady state UV/vis absorption spectroscopy, fluorescence emission spectroscopy, electrochemical characterization, and nanosecond transient absorption spectroscopy. Singlet energy transfer from the Bodipy antenna to the C 60 module was confirmed by fluorescence quenching studies. The intersystem crossing of the latter produced the triplet excited state. The nanosecond transient absorption spectroscopy showed that the triplet state is either localized on the C 60 module (for assembly B-1·C-1 ), or on the styryl-Bodipy antenna (for assemblies B-2·C-1 and B-3·C-1 ). Intra-assembly forward-backward (ping-pong) singlet/triplet energy transfer was proposed. In contrast to the H-bonding assemblies, slow triplet energy transfer was observed for the non-hydrogen bonding mixtures. As a proof of concept, these supramolecular assemblies were used as triplet photosensitizers for triplet-triplet annihilation upconversion.

Nanodiamonds + bacteriochlorin as an infrared photosensitizer for deep-lying tumor diagnostics and therapy

NASA Astrophysics Data System (ADS)

Sharova, A. S.; Maklygina, YU S.; Lisichkin, G. V.; Mingalev, P. G.; Loschenov, V. B.

2016-08-01

The spectroscopic properties of potentially perspective nanostructure: diamond nanoparticles with a surface layer of IR-photosensitizer, bacteriochlorin, were experimentally investigated in this study. Such specific structure of the object encourages enhancement of the drug tropism to the tumor, as well as increasing of photodynamic penetration depth. The size distribution spectra of diamond nanoparticles; diamond nanoparticles, artificially covered with bacteriochlorin molecules layer, in aqueous solution, were obtained during the study. Based on the absorption and fluorescence spectra analysis, the benefits of functional nanostructure as a drug for deep-lying tumor diagnostics and therapy were reviewed.

Impact of natural photosensitizer extraction solvent upon light absorbance in dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Suhaimi, Suriati; Mohamed Siddick, Siti Zubaidah; Ahmad Hambali, Nor Azura Malini; Retnasamy, Vithyacharan; Abdul Wahid, Mohamad Halim; Mohamad Shahimin, Mukhzeer

2017-02-01

Natural pigmentations of Ardisia, Bawang Sabrang, Harum Manis mango, Oxalis Triangularis and Rosella were used to study the general trend in performance of dyes as a photosensitizer in the application of dye-sensitized solar cells (DSSCs) based on optical light absorbance and photoelectrochemical characteristics. From the Ultraviolet-Visible Spectrophotometer with the recorded absorption measurements in the range between 400 nm to 800 nm, the dyes extracted from Rosella and Oxalis Triangularis in water solvent exhibited the conversion efficiency up to 0.68% and 0.67%, respectively. The light absorbance peak for dye extracted from Ardisia, Bawang Sabrang, Oxalis Triangularis and Rosella in water and ethanol solvent resulted in the range between 500 nm to 650 nm, while the Harum Manis mango resulted in the broader spectra in both water and ethanol solvent. The light absorbance spectra of each the dyes shows shifted wavelength spectrum when the extracted dye is adsorbed onto TiO2 film surface that might influenced the absorption of light by TiO2 particle in the visible region. The capabilities of the dyes to absorb light when bonded onto the TiO2 photoanode was found to be significant with the current-voltage conversion of the cell. The results demonstrates just the tip of the vastness of natural dyes' (native to tropical region) feasibility and applicability as a photosensitizer.

Physical Stability, Autoxidation, and Photosensitized Oxidation of ω-3 Oils in Nanoemulsions Prepared with Natural and Synthetic Surfactants.

PubMed

Uluata, Sibel; McClements, D Julian; Decker, Eric A

2015-10-28

The food industry is interested in the utilization of nanoemulsions stabilized by natural emulsifiers, but little research has been conducted to determine the oxidative stability of such emulsions. In this study, two natural (lecithin and quillaja saponin) and two synthetic (Tween 80 and sodium dodecyl sulfate) surfactants were used to fabricate omega-3 nanoemulsion using high pressure homogenization (microfluidization). Initially, all the nanoemulsions contained small (d from 45 to 89 nm) and anionic (ζ-potential from -8 to -65 mV) lipid droplets (pH 7). The effect of pH, ionic strength, and temperature on the physical stability of the nanoemulsion system was examined. Nanoemulsion stabilized with Tween 80, quillaja saponin, or sodium dodecyl sulfate (SDS) exhibited no major changes in particle size or visible creaming in the pH range of 3 to 8. All nanoemulsions were relatively stable to salt addition (0 to 500 mM NaCl, pH 7.0). Nanoemulsions stabilized with SDS and quillaja saponin were stable to heating (30 to 90 °C). The impact of surfactant type on lipid oxidation was determined in the presence and absence of the singlet oxygen photosensitizers, riboflavin, and rose bengal. Riboflavin and rose bengal accelerated lipid oxidation when compare to samples without photosensitizers. Lipid hydroperoxide formation followed the order Tween 80 > SDS > lecithin > quillaja saponin, and propanal formation followed the order lecithin > Tween 80 > SDS > quillaja saponin at 37 °C for autoxidation. The same order of oxidative stability was observed in the presence of photosensitized oxidation promoted by riboflavin. Quillaja saponin consistently produced the most oxidatively stable emulsions, which could be due to its high free radical scavenging capacity.

Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

PubMed

Shirmanova, Marina; Yuzhakova, Diana; Snopova, Ludmila; Perelman, Gregory; Serebrovskaya, Ekaterina; Lukyanov, Konstantin; Turchin, Ilya; Subochev, Pavel; Lukyanov, Sergey; Kamensky, Vladislav; Zagaynova, Elena

2015-01-01

The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.

Is colour modulation an independent factor in human visual photosensitivity?

PubMed

Parra, Jaime; Lopes da Silva, Fernando H; Stroink, Hans; Kalitzin, Stiliyan

2007-06-01

Considering that the role of colour in photosensitive epilepsy (PSE) remains unclear, we designed a study to determine the potential of different colours, colour combinations and white light to trigger photoparoxysmal responses (PPRs) under stringent controlled conditions. After assessing their photosensitivity to stroboscopic white light and black and white patterns, we studied 43 consecutive PSE patients (mean age 19 years, 34 women), using a specially designed colour stimulator. Stimuli included: pulse trains between 10 and 30 Hz of white light and of all primary colours, and also isoluminant alternating time-sequences of colours. Illuminance was kept constant at 100 lux. A progressive stepwise increase of the modulation-depth (MD) of the stimuli was used to determine PPRs threshold. Whereas all the 43 patients were found to be sensitive during the stroboscopic and pattern protocol, only 25 showed PPRs (Waltz's score >2) at least in one session when studied with the colour stimulator. Coloured stimuli elicited PPRs in all these patients, whereas white light did so only in 17 patients. Of the primary colours, red elicited more PPRs (54 in 22 patients) and at a lower MD (max Z-score 0.93 at 10 Hz). Of the alternating sequences, the red-blue was the most provocative stimulus, especially below 30 Hz (100% of patients, max Z-score: 1.65 at 15 Hz). Blue-green was the least provocative stimulus, since it elicited only seven PPRs in seven (28%) patients (max Z-score 0.44 at 10 Hz). Sensitivity to alternating colours was not correlated to sensitivity to individual colours. We conclude that colour sensitivity follows two different mechanisms: one, dependent on colour modulation, plays a role at lower frequencies (<30 Hz). Another, dependent on single-colour light intensity modulation correlates to white light sensitivity and is activated at higher frequencies. Our results suggest that the prescription of spectacles with coloured lenses, tailored to the patient, can be an

First Quantification of Imidazoles in Ambient Aerosol Particles: Potential Photosensitizers, Brown Carbon Constituents, and Hazardous Components.

PubMed

Teich, Monique; van Pinxteren, Dominik; Kecorius, Simonas; Wang, Zhibin; Herrmann, Hartmut

2016-02-02

Imidazoles are widely discussed in recent literature. They have been studied as a secondary product of the reaction of dicarbonyls with nitrogen containing compounds in a number of laboratory studies, potentially acting as photosensitizers triggering secondary organic aerosol growth and are forming constituents of light absorbing brown carbon. Despite the knowledge from laboratory studies, no quantitative information about imidazoles in ambient aerosol particles is available. Within the present study, five imidazoles (1-butylimidazole, 1-ethylimidazole, 2-ethylimidazole, imidazol-2-carboxaldehyde, and 4(5)-methylimidazole) were successfully identified and quantified for the first time in ambient aerosol samples from different environments in Europe and China. Their concentrations range between 0.2 and 14 ng/m(3). 4(5)-Methylimidazole was found to be the most abundant imidazole. The occurrence of imidazoles seems to be favored at sites with strong biomass burning influence or connected to more polluted air masses. No connection was found between aerosol particle pH and imidazole concentration. Our work corroborates the laboratory studies by showing that imidazoles are present in ambient aerosol samples in measurable amounts. Moreover, it further motivates to explore the potential photosensitizing properties of small alkyl-substituted imidazoles.

Comparison of Riboflavin and Toluidine Blue O as Photosensitizers for Photoactivated Disinfection on Endodontic and Periodontal Pathogens In Vitro.

PubMed

Nielsen, Henrik Krarup; Garcia, Javier; Væth, Michael; Schlafer, Sebastian

2015-01-01

Photoactivated disinfection has a strong local antimicrobial effect. In the field of dentistry it is an emerging adjunct to mechanical debridement during endodontic and periodontal treatment. In the present study, we investigate the effect of photoactivated disinfection using riboflavin as a photosensitizer and blue LED light for activation, and compare it to photoactivated disinfection with the widely used combination of toluidine blue O and red light. Riboflavin is highly biocompatible and can be activated with LED lamps at hand in the dental office. To date, no reports are available on the antimicrobial effect of photoactivated disinfection using riboflavin/blue light on oral microorganisms. Planktonic cultures of eight organisms frequently isolated from periodontal and/or endodontic lesions (Aggregatibacter actinomycetemcomitans, Candida albicans, Enterococcus faecalis, Escherischia coli, Lactobacillus paracasei, Porphyromonas gingivalis, Prevotella intermedia and Propionibacterium acnes) were subjected to photoactivated disinfection with riboflavin/blue light and toluidine blue O/red light, and survival rates were determined by CFU counts. Within the limited irradiation time of one minute, photoactivated disinfection with riboflavin/blue light only resulted in minor reductions in CFU counts, whereas full kills were achieved for all organisms when using toluidine blue O/red light. The black pigmented anaerobes P. gingivalis and P. intermedia were eradicated completely by riboflavin/blue light, but also by blue light treatment alone, suggesting that endogenous chromophores acted as photosensitizers in these bacteria. On the basis of our results, riboflavin cannot be recommended as a photosensitizer used for photoactivated disinfection of periodontal or endodontic infections.

FIBER OPTICS: Role of point defects in the photosensitivity of hydrogen-loaded phosphosilicate glass

NASA Astrophysics Data System (ADS)

Larionov, Yu V.

2010-08-01

It is shown that point defect modifications in hydrogen-loaded phosphosilicate glass (PSG) do not play a central role in determining its photosensitivity. Photochemical reactions that involve a two-step point defect modification and pre-exposure effect are incapable of accounting for photoinduced refractive index changes. It seems likely that a key role in UV-induced refractive index modifications is played by structural changes in the PSG network. Experimental data are presented that demonstrate intricate network rearrangement dynamics during UV exposure of PSG.

Dispersion of the Photosensitizer 5,10,15,20-Tetrakis(4-Sulfonatophenyl)-porphyrin by the Amphiphilic Polymer Poly(vinylpirrolidone) in Highly Porous Solid Materials Designed for Photodynamic Therapy.

PubMed

Díaz, Claudia; Catalán-Toledo, José; Flores, Mario E; Orellana, Sandra L; Pesenti, Héctor; Lisoni, Judit; Moreno-Villoslada, Ignacio

2017-08-03

The ability of the amphiphilic and biocompatible poly(vinylpyrrolidone) to avoid self-aggregation of the photosensitizer 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin in aqueous solution in the presence of the biocompatible polycation chitosan, polymer that induces the dye self-aggregation, is shown. This is related to the tendency of the dye to undergo preferential solvation by the amphiphilic polymer. Importantly, the dispersant ability of this polymer is transferred to the solid state. Thus, aerogels made of the biocompatible polymers chitosan and chondroitin sulfate, and containing the photosensitizer dispersed by the amphiphilic polymer have been synthesized. Production of reactive oxygen species by the aerogel containing the amphiphilic polymer was faster than when the polymer was absent, correlating with the relative concentration of dyes dispersed as monomers. The aerogels presented here constitute low cost biocompatible materials bearing a conventional photosensitizer for photodynamic therapy, easy to produce, store, transport, and manage in clinical practice.

Photodegradation of environmental mutagens by visible irradiation in the presence of xanthene dyes as photosensitizers.

PubMed

Odo, Junichi; Torimoto, Sei-ichi; Nakanishi, Suguru; Niitani, Tomoya; Aoki, Hiroyuki; Inoguchi, Masahiko; Yamasaki, Yu

2012-01-01

The photodegradation of environmental mutagens, such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), and 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), was investigated by visible irradiation in the presence of xanthene dyes as photosensitizers. Although the environmental mutagens themselves were very stable during visible irradiation under the conditions in this study, they were effectively photodegraded in the presence of the xanthene dyes (erythrosine, rose bengal, and phloxine). Moreover, photodegradation of the mutagens was further enhanced for xanthene dyes loaded onto a water-soluble diethylaminoethyl (DEAE)-dextran anion-exchanger via ionic interactions (xanthene-dyeDEX). Photodegradation was inhibited by O2 removal from the reaction solution. In ESR spin-trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a trapping reagent, signals characteristic of DMPO-•OH (hydroxyl radical) were observed in the presence of xanthene-dyeDEX. These results suggest that reactive oxygen species derived from O2, such as singlet molecular oxygen (•1O2) and/or •OH, were active participants in photodegradation of the mutagens in the presence of xanthene dyes or xanthene-dyeDEX.

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

PubMed Central

Daiutolo, Brittany V.; Tyburski, Ashley; Clark, Shannon W.

2016-01-01

Abstract The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle (p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT (p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia (p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days (p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH. PMID:26472135

Naphthalocyanine-complexes as potential photosensitizers for PDT of tumors

NASA Astrophysics Data System (ADS)

Shopova, Maria; Woehrle, Dieter; Mantareva, Vanya; Mueller, Silke

1999-07-01

In the present paper information about the synthesis and results on the pharmacokinetic and experimental photodynamic therapy (PDT) of naphthalocyanines are given. The photodynamic activity of differently substituted zinc(II)- and silicon(IV)-naphthalocyanines using liposomes or Cremophor EL as drug-delivery systems is shown on different tumor models. For the evaluation of the phototherapeutic effect different assessment criteria were used, including light and electron microscope observations. The main conclusions which can be arrived at on the basis of our findings are the following: silicon(IV)-naphthalocyanine seems to be not a very effective tumor sensitizer, especially in the treatment o pigmented melanoma, while zinc(II)-naphthalocyanines appear to be very promising for PDT of tumors. Their selective targeting and slow clearance from tumor tissue, fast clearance from skin and pronounced phototherapeutic effect on different tumor models and especially at melanotic tumors, even after application of low drug doses, make this group of photosensitizers very attractive for successful PDT of cancer.

The photosensitizer talaporfinum caused microvascular embolization for photodynamic therapy

NASA Astrophysics Data System (ADS)

Li, Liming; Aizawa, Katsuo

2005-07-01

Photodynamic therapy (PDT) has been evolving rapidly in the recent years. A second-generation Photosensitizer mono-1-aspartyl chlorine 6 (Talaporfin / Npe6 / ME2906, Japan Meiji Seika, Ltd.) has been sanctified for the lung cancer clinical PDT by the Japan Ministry of Health, Labor and Welfare. In this paper, Talaporfin was injected to the implant cancer of a mouse a Talaporfin dose of 5mg/kg through intravenous. After 6 hours, the fluorescence images of the mouse were observed with a microscope and a 664 nm diode laser. Effects of therapy were clarified using the different irradiation energies of the laser (50, 100, 200 J/cm2). Both in plasma and in cancer, the concentrations of Talaporfin were analyzed using High Performance Liquid Chromatography (HPLC). Authors find that the higher concentrations of Talaporfin in plasma, the better PDD effect. It is experimentally verified that local microvascular embolisms in the cancer are formed for photodynamic therapy after the Talaporfin injection and the laser irradiation.

Complex dynamics and enhanced photosensitivity in a modified Belousov-Zhabotinsky reaction

NASA Astrophysics Data System (ADS)

Li, Nan; Zhao, Jinpei; Wang, Jichang

2008-06-01

This study presents an experimental investigation of nonlinear dynamics in a modified Belousov-Zhabotinsky (BZ) reaction, in which the addition of 1,4-benzoquinone induced various complex behaviors such as mixed-mode oscillations and consecutive period-adding bifurcations. In addition, the presence of 1,4-benzoquinone significantly enhanced the photosensitivity of the ferroin-catalyzed BZ system, in which light-induced transitions between simple and complex oscillations have been achieved. Mechanistic study suggests that the influence of benzoquinone may arise from its interactions with the metal catalyst ferroin/ferriin, where cyclic voltammograms illustrate that the presence of benzoquinone causes an increase in the redox potential of ferroin/ferriin couple, which may consequently alternate the oxidation and reduction paths of the catalyst.

Fabrication and investigation of photosensitive MoOx/n-CdTe heterojunctions

NASA Astrophysics Data System (ADS)

Solovan, M. M.; Gavaleshko, N. M.; Brus, V. V.; Mostovyi, A. I.; Maryanchuk, P. D.; Tresso, E.

2016-10-01

MoOx/n-CdTe photosensitive heterostructures were prepared by the deposition of molybdenum oxide thin films onto n-type single-crystal CdTe substrates by DC reactive magnetron sputtering. The obtained heterojunctions possessed sharply defined rectifying properties with the rectification ration RR ˜ 106. The temperature dependences of the height of the potential barrier and series resistance of the MoOx/CdTe heterojunctions were investigated. The dominating current transport mechanisms through the heterojunctions were determined at forward and reverse biases. The analysis of capacitance-voltage (C-V) characteristics, measured at different frequencies of the small amplitude AC signal and corrected by the effect of the series resistance, provided evidence of the presence of electrically charged interface states, which significantly affect the measured capacitance.

Free-standing coating patterns fabricated by ultraviolet contact lithography using photosensitive sol-gel coatings

NASA Astrophysics Data System (ADS)

Xiang, Youlai; Du, Ai; Li, Xiaoguang; Sun, Wei; Wu, Shuai; Li, Tiemin; Liu, Mingfang; Zhou, Bin

2017-07-01

Photosensitive ZrO2-SiO2 hybrid sol-gel coatings containing large contents of chelating rings were prepared by using the zirconium n-butoxide (TBOZ) and methyltriethoxysilane (MTES) as hybrid precursors, and benzoylacetone (BZAC) as chelating agent. The change of ultraviolet (UV) absorption spectra, chemical composition, and optical properties of ZrO2-SiO2 hybrid sol-gel coatings were analyzed before and after UV exposure and calcination. The refractive index of the ZrO2-SiO2 hybrid gel coatings decreased from 1.673 to 1.561 with the increase of the molar content of MTES in precursors. The sol-gel coating patterns with the periods of 20.24 μm, 10.11 μm and 3.99 μm on the PAMS substrates were firstly obtained by using the photosensitive ZrO2-SiO2 hybrid sol-gel films as fundamental materials through a process of UV contact lithography with photo masks and etching with ethanol. Finally, the free-standing gel coating patterns supported by copper grids, with the period of 12.70 μm and line width of 4.93 μm, and the period of 14.20 μm and line width of 3.82 μm, were obtained by removing the PAMS thermal degradation sacrifice layer after being calcined at 330 °C. Micrometer-periodic free-standing gel coating patterns with different structure have potential applications in the laser physical experiments.

Inorganic photosensitizer coupled Gd-based upconversion luminescent nanocomposites for in vivo magnetic resonance imaging and near-infrared-responsive photodynamic therapy in cancers.

PubMed

Zhang, Ling'e; Zeng, Leyong; Pan, Yuanwei; Luo, Song; Ren, Wenzhi; Gong, An; Ma, Xuehua; Liang, Hongze; Lu, Guangming; Wu, Aiguo

2015-03-01

Inorganic photosensitizer coupled Gd-based upconversion luminescent (UCL) nanocomposites have potential application for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT) of cancers using the light stability and biocompatibility of TiO2 inorganic photosensitizer. However, TiO2 inorganic photosensitizer could only be excited by ultraviolet (UV) light, which was harmful and weakly penetrable in tissues. In this work, folic acid (FA)-targeted NaGdF4:Yb/Tm@SiO2@TiO2 nanocomposites (FA-Gd-Si-Ti NPs) were constructed and synthesized for both in vivo MRI and near infrared (NIR)-responsive inorganic PDT, in which TiO2 component could be excited by NIR light due to the UCL performance of NaGdF4:Yb/Tm component converting NIR to UV light. The results showed the as-prepared FA-Gd-Si-Ti NPs had good biocompatibility in vitro and in vivo. Moreover, MR study indicated that FA-Gd-Si-Ti NPs were good T1-weighted MRI contrast agents with high longitudinal relaxivity (r1) of 4.53 mm(-1) s(-1), also in vivo MRI of nude mice showed "bright" signal in MCF-7 tumor. Under the irradiation of 980 nm laser at the power density of 0.6 W/cm(2) for 20 min, the viability of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease from about 90 % to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7 tumor-bearing nude mice model showed that the inhibition ratio of tumors injected with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment, compared with that of nude mice in control group. Based on the deep penetration of NIR light and the good biocompatibility of TiO2 inorganic photosensitizer, the as-prepared FA-Gd-Si-Ti NPs could have potential applications in both MRI and NIR-responsive PDT of cancers in deep tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Photosensitive biosensor array system using optical addressing without an addressing circuit on array biochips

NASA Astrophysics Data System (ADS)

Ahn, Chang-Geun; Ah, Chil Seong; Kim, Tae-Youb; Park, Chan Woo; Yang, Jong-Heon; Kim, Ansoon; Sung, Gun Yong

2010-09-01

This paper introduces a photosensitive biosensor array system with a simple photodiode array that detects photocurrent changes caused by reactions between probe and target molecules. Using optical addressing, the addressing circuit on the array chip is removed for low-cost application, and real cell addressing is achieved using an externally located computer-controllable light-emitting diode array module. The fabricated biosensor array chip shows a good dynamic range of 1-100 ng/mL under prostate-specific antigen detection, with an on-chip resolution of roughly 1 ng/mL.

Halogen atom effect on the photophysical properties of substituted aza-BODIPY derivatives.

PubMed

De Simone, B C; Mazzone, G; Pirillo, J; Russo, N; Sicilia, E

2017-01-18

The influence of halogen atom substitution (Br and I), in different amounts and positions in an aza-BODIPY skeleton, on the photophysical properties of some aza-BODIPY derivatives has been investigated by using density functional theory and its time-dependent extension. The heavy atom effect on excitation energies, singlet-triplet energy gaps and spin-orbit matrix elements has been considered. The maximum absorption within the therapeutic window has been confirmed for all the aza-BODIPY derivatives. The feasible intersystem spin crossing pathways for the population of the lowest triplet state, that will depend on the values of the spin-orbit matrix elements, the energy gap as well as the orbital composition of the involved states have been found to most likely involve the S 1 and T 1 or T 2 states. The outcomes of computations support the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy.

Intracellular photoinduced oxidative stress by zinc phthalocyanine photosensitization: a study of the early events in real time using confocal microscopy

NASA Astrophysics Data System (ADS)

Alexandratou, Eleni; Yova, Dido; Handris, Panagiotis; Kletsas, Dimitris; Loukas, Spyros

2003-10-01

Oxidative stress has been implicated in several biological and pathological aspects. Reactive oxygen species (ROS) have been proposed to act as signal transduction molecules activating reactions leading to cell rescue or to cell apoptosis/necrosis. In the present study, oxidative stress was induced by photosensitization of zinc phthalocyanine (ZnPc) in human fibroblasts using a photodynamic dose that did not lead to apoptosis or necrosis. The induction of oxidative stress was performed at the microscope stage in preassigned time. The cascade of phenomena evoked was studied in real time and at the single cell level using confocal laser scanning microscopy. Using specific vital fluorescent probes, alterations induced by oxidative stress in mitochondria membrane potential, in intracellular pH and in calcium concentration were recorded. Image processing and analysis techniques were used to quantify the observed changes. Subcellular localization of the photosensitizer was studied in order to determine the primary and immediate ROS target. It was found that ZnPc is mainly localized in the mitochondria region.

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation.

PubMed

Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

2018-01-01

Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA's phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans . We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

PubMed Central

Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

2018-01-01

Background Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. Results A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans. We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and

Polymer-lipid-PEG hybrid nanoparticles as photosensitizer carrier for photodynamic therapy.

PubMed

Pramual, Sasivimon; Lirdprapamongkol, Kriengsak; Svasti, Jisnuson; Bergkvist, Magnus; Jouan-Hureaux, Valérie; Arnoux, Philippe; Frochot, Céline; Barberi-Heyob, Muriel; Niamsiri, Nuttawee

2017-08-01

Polymer-lipid-PEG hybrid nanoparticles were investigated as carriers for the photosensitizer (PS), 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,23H-porphine (pTHPP) for use in photodynamic therapy (PDT). A self-assembled nanoprecipitation technique was used for preparing two types of core polymers poly(d,l-lactide-co-glycolide) (PLGA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) with lipid-PEG as stabilizer. The resulting nanoparticles had an average particle size of 88.5±3.4nm for PLGA and 215.0±6.3nm for PHBV. Both nanoparticles exhibited a core-shell structure under TEM with high zeta potential and loading efficiency. X-ray powder diffraction analysis showed that the encapsulated pTHPP molecules in polymeric nanoparticles no longer had peaks of free pTHPP in the crystalline state. The pTHPP molecules encapsulated inside the polymeric core demonstrated improved photophysical properties in terms of singlet oxygen generation and cellular uptake rate in a FTC-133 human thyroid carcinoma cell line, compared to non-encapsulated pTHPP. The pTHPP-loaded polymer-lipid-PEG nanoparticles showed better in vitro phototoxicity compared to free pTHPP, in both time- and concentration-dependent manners. Overall, this study provides detailed analysis of the photophysical properties of pTHPP molecules when entrapped within either PLGA or PHBV nanoparticle cores, and demonstrates the effectiveness of these systems for delivery of photosensitizers. The two polymeric systems may have different potential benefits, when used with cancer cells. For instance, the pTHPP-loaded PLGA system requires only a short time to show a PDT effect and may be suitable for topical PDT, while the delayed photo-induced cytotoxic effect of the pTHPP-loaded PHBV system may be more suitable for cancer solid tumors. Hence, both pTHPP-encapsulated polymer-lipid-PEG nanoparticles can be considered promising delivery systems for PDT cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel Methods to Incorporate Photosensitizers Into Nanocarriers for Cancer Treatment by Photodynamic Therapy

PubMed Central

Wang, Shouyan; Fan, Wenzhe; Kim, Gwangseong; Hah, Hoe Jin; Lee, Yong-Eun Koo; Kopelman, Raoul; Ethirajan, Manivannan; Gupta, Anurag; Goswami, Lalit N.; Pera, Paula; Morgan, Janet; Pandey, Ravindra K.

2013-01-01

Objective A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). Materials and Methods HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. Results HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 ± 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. Conclusions Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT. Lasers Surg. Med. 43:686–695, 2011. PMID:22057496

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

NASA Astrophysics Data System (ADS)

Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

1995-03-01

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones.

PubMed

Melo, Wanessa C M A; Santos, Mariana Bastos Dos; Marques, Beatriz de Carvalho; Regasini, Luis Octávio; Giannini, Maria José Soares Mendes; Almeida, Ana Marisa Fusco

2017-06-01

Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95μgmL -1 ) incubated by 15min and irradiated with LED 450nm with 24Jcm -2 . Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Mild skin photosensitivity in cancer patients following injection of Photochlor (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a; HPPH) for photodynamic therapy.

PubMed

Bellnier, David A; Greco, William R; Nava, Hector; Loewen, Gregory M; Oseroff, Allan R; Dougherty, Thomas J

2006-01-01

To measure skin photosensitivity in cancer patients infused with the new second-generation photodynamic sensitizer Photochlor (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a). A major disadvantage of using the clinically approved photosensitizer Photofrin is potentially prolonged and sometimes severe cutaneous phototoxicity. Forty-eight patients enrolled in Phases 1 and 2 clinical trials underwent two or more exposures to four graded doses (44.4, 66.6, 88.8 or 133.2 J/cm2) of artificial solar-spectrum light (SSL) before and after administration of Photochlor at a dose of 2.5, 3, 4, 5 or 6 mg/m2 . The most severe skin response, experienced by only six of the subjects, was limited to erythema without edema and could only be elicited by exposure to the highest light dose. Conversely, eight subjects had no discernible reaction to SSL at any light dose. For nearly all the patients, the peak skin response was obtained when the interval between sensitizer injection and exposure to SSL was 1 day and, generally, their sensitivity to SSL decreased with increasing sensitizer-light interval. For example, a 2-day sensitizer-SSL interval resulted in less severe reactions than those obtained with the 1-day interval in 79% of the subjects, while 90% of the subjects exposed to SSL 3 days after Photochlor infusion had responses that were less severe than those obtained with either the 1- or 2-day sensitizer-SSL interval. Photochlor, at clinically effective antitumor doses, causes only mild skin photosensitivity that declines rapidly over a few days.

Photoinactivation of Gram positive and Gram negative bacteria with the antimicrobial peptide (KLAKLAK)(2) conjugated to the hydrophilic photosensitizer eosin Y.

PubMed

Johnson, Gregory A; Muthukrishnan, Nandhini; Pellois, Jean-Philippe

2013-01-16

We test the hypothesis that the antimicrobial peptide (KLAKLAK)(2) enhances the photodynamic activity of the photosensitizer eosin Y upon conjugation. The conjugate eosin-(KLAKLAK)(2) was obtained by solid-phase peptide synthesis. Photoinactivation assays were performed against the Gram-negative bacteria Escherichia coli , Pseudomonas aeruginosa , and multidrug resistant Acinetobacter baumannii AYE, as well as the Gram-positive bacteria Staphylococcus aureus , and Staphylococcus epidermidis . Partitioning assays were performed with E. coli and S. aureus . Photohemolysis and photokilling assays were also performed to assess the photodynamic activity of the conjugate toward mammalian cells. Eosin-(KLAKLAK)(2) photoinactivates 99.999% of 10(8) CFU/mL of most bacteria tested at a concentration of 1 μM or below. In contrast, neither eosin Y nor (KLAKLAK)(2) cause any significant photoinactivation under similar conditions. The increase in photodynamic activity of the photosensitizer conferred by the antimicrobial peptide is in part due to the fact that (KLAKLAK)(2) promotes the association of eosin Y to bacteria. Eosin-(KLAKLAK)(2) does not significantly associate with red blood cells or the cultured mammalian cell lines HaCaT, COS-7, and COLO 316. Consequently, little photodamage or photokilling is observed with these cells under conditions for which bacterial photoinactivation is achieved. The peptide (KLAKLAK)(2) therefore significantly enhances the photodynamic activity of eosin Y toward both Gram-positive and Gram-negative bacteria while interacting minimally with human cells. Overall, our results suggest that antimicrobial peptides such as (KLAKLAK)(2) might serve as attractive agents that can target photosensitizers to bacteria specifically.

Photosensitized Protein-Damaging Activity, Cytotoxicity, and Antitumor Effects of P(V)porphyrins Using Long-Wavelength Visible Light through Electron Transfer.

PubMed

Hirakawa, Kazutaka; Ouyang, Dongyan; Ibuki, Yuko; Hirohara, Shiho; Okazaki, Shigetoshi; Kono, Eiji; Kanayama, Naohiro; Nakazaki, Jotaro; Segawa, Hiroshi

2018-05-21

Photodynamic therapy (PDT) is a less-invasive treatment for cancer through the administration of less-toxic porphyrins and visible-light irradiation. Photosensitized damage of biomacromolecules through singlet oxygen ( 1 O 2 ) generation induces cancer cell death. However, a large quantity of porphyrin photosensitizer is required, and the treatment effect is restricted under a hypoxic cellular condition. Here we report the phototoxic activity of P(V)porphyrins: dichloroP(V)tetrakis(4-methoxyphenyl)porphyrin (CLP(V)TMPP), dimethoxyP(V)tetrakis(4-methoxyphenyl)porphyrin (MEP(V)TMPP), and diethyleneglycoxyP(V)tetrakis(4-methoxyphenyl)porphyrin (EGP(V)TMPP). These P(V)porphyrins damaged the tryptophan residue of human serum albumin (HSA) under the irradiation of long-wavelength visible light (>630 nm). This protein photodamage was barely inhibited by sodium azide, a quencher of 1 O 2 . Fluorescence lifetimes of P(V)porphyrins with or without HSA and their redox potentials supported the electron-transfer-mediated oxidation of protein. The photocytotoxicity of these P(V)porphyrins to HeLa cells was also demonstrated. CLP(V)TMPP did not exhibit photocytotoxicity to HaCaT, a cultured human skin cell, and MEP(V)TMPP and EGP(V)TMPP did; however, cellular DNA damage was barely observed. In addition, a significant PDT effect of these P(V) porphyrins on a mouse tumor model comparable with the traditional photosensitizer was also demonstrated. These findings suggest the cancer selectivity of these P(V)porphyrins and lower carcinogenic risk to normal cells. Electron-transfer-mediated oxidation of biomacromolecules by P(V)porphyrins using long-wavelength visible light should be advantageous for PDT of hypoxic tumor.

Fructose as a novel photosensitizer: Characterization of reactive oxygen species and an application in degradation of diuron and chlorpyrifos.

PubMed

Nayak, Shaila; Muniz, Juan; Sales, Christopher M; Tikekar, Rohan V

2016-02-01

The objective of this study was to identify reactive oxygen species (ROS) generated from the exposure of fructose solution to the 254 nm ultraviolet (UV) light and evaluate whether fructose can be used as a photosensitizer for accelerated photo-degradation of diuron and chlorpyrifos. We demonstrated that hydrogen peroxide, singlet oxygen ((1)O2) and acidic photolysis products were generated upon UV exposure of fructose. Consistent with these findings, UV induced degradation of chlorpyrifos and diuron was accelerated by the presence of 500 mM fructose. The average first order photo-degradation rate constants in the absence and presence of 500 mM fructose were 0.92 and 2.07 min(-1) respectively for diuron and 0.04 and 0.07 min(-1) for chlorpyrifos. The quantum yields (ɸ) for direct photo-degradation of diuron and chlorpyrifos were 0.003 and 0.001 respectively. In the presence of 500 mM fructose, these values increased to 0.006 and 0.002 respectively. Thus, fructose may be an effective photosensitizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative photodynamic therapy cytotoxicity of mannose-conjugated chlorin and talaporfin sodium in cultured human and rat cells.

PubMed

Shinoda, Yo; Takahashi, Tsutomu; Akimoto, Jiro; Ichikawa, Megumi; Yamazaki, Hiromi; Narumi, Atsushi; Yano, Shigenobu; Fujiwara, Yasuyuki

2017-01-01

Photodynamic therapy (PDT) is a Food and Drug Administration authorized method for cancer treatment, which uses photosensitizer and laser photo-irradiation to generate reactive oxygen species to induce cell death in tumors. Photosensitizers have been progressively developed, from first to third generation, with improvements in cell specificity, reduced side effects and toxicity, increased sensitivity for irradiation and reduced persistence of photosensitizer in healthy cells. These improvements have been achieved by basic comparative experiments between current and novel photosensitizers using cell lines; however, photosensitizers should be carefully evaluated because they may have cell type specificity. In the present study, we compared a third-generation photosensitizer, β-mannose-conjugated chlorin (β-M-chlorin), with the second generation, talaporfin sodium (NPe6), using seven different rat and human cell lines and a neuronal/glial primary culture prepared from rat embryos. NPe6 was more effective than β-M-chlorin in human-derived cell lines, and β-M-chlorin was more effective than NPe6 in rat primary cultures and rat-derived cell lines, except for the rat pheochromocytoma cell line, PC12. These differences of phototoxicity in different cell types are not because of differences in photosensitivity between the photosensitizers, but rather are associated with different distribution and accumulation rates in the different cell types. These data suggest that evaluation of photosensitizers for PDT should be carried out using as large a variety of cell types as possible because each photosensitizer may have cell type specificity.

A Highly Efficient and Photostable Photosensitizer with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Anticancer Therapy.

PubMed

Wu, Wenbo; Mao, Duo; Hu, Fang; Xu, Shidang; Chen, Chao; Zhang, Chong-Jing; Cheng, Xiamin; Yuan, Youyong; Ding, Dan; Kong, Deling; Liu, Bin

2017-09-01

Photodynamic therapy (PDT), which relies on photosensitizers (PS) and light to generate reactive oxygen species to kill cancer cells or bacteria, has attracted much attention in recent years. PSs with both bright emission and efficient singlet oxygen generation have also been used for image-guided PDT. However, simultaneously achieving effective 1 O 2 generation, long wavelength absorption, and stable near-infrared (NIR) emission with low dark toxicity in a single PS remains challenging. In addition, it is well known that when traditional PSs are made into nanoparticles, they encounter quenched fluorescence and reduced 1 O 2 production. In this contribution, these challenging issues have been successfully addressed through designing the first photostable photosensitizer with aggregation-induced NIR emission and very effective 1 O 2 generation in aggregate state. The yielded nanoparticles show very effective 1 O 2 generation, bright NIR fluorescence centered at 820 nm, excellent photostability, good biocompatibility, and negligible dark in vivo toxicity. Both in vitro and in vivo experiments prove that the nanoparticles are excellent candidates for image-guided photodynamic anticancer therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hybrid TiO2 -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions.

PubMed

Gilson, Rebecca C; Black, Kvar C L; Lane, Daniel D; Achilefu, Samuel

2017-08-28

Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS-producing hybrid nanoparticle-based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO 2 nanoparticle afforded TiO 2 -N3. Upon exposure of TiO 2 -N3 to light, the N3 injected electrons into TiO 2 to produce three- and four-fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO 2 at 160 mmHg. TiO 2 -N3 maintained three-fold higher hydroxyl radicals than TiO 2 under hypoxic conditions via N3-facilitated electron-hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO 2 from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins.

PubMed

Luiza Andreazza, Nathalia; Vevert-Bizet, Christine; Bourg-Heckly, Geneviève; Sureau, Franck; José Salvador, Marcos; Bonneau, Stephanie

2016-08-20

Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake. Copyright © 2016. Published by Elsevier B.V.

Influence of temperature on the myocardial cells death by an extracellular talaporfin sodium-induced photosensitization reaction

NASA Astrophysics Data System (ADS)

Ogawa, Emiyu; Takenoya, Hiromi; Arai, Tsunenori

2016-03-01

We have proposed to apply the photosensitization reaction in myocardium interstitial fluid using talaporfin sodium to realize less-heated electrical conduction block for a tachyarrhythmia treatment: PD Ablation®. The cytotoxicity of the extracellular photosensitization reaction efficiency may change by the talaporfin sodium binding with serum proteins. These binding would change with solution temperature. We investigated the binding behavior of talaporfin sodium with human serum albumin (HSA), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) changing solution temperature from 17 to 37°C. We also studied the photocytotoxicity change by solution temperature of 17 and 37°C measuring cell lethality by WST assay using fetal bovine serum. The binding ratio of talaporfin sodium with HDL and LDL decreased 6.3% and 12.8% with temperature increasing from 17 to 37°C. There was no significant difference in the case of HSA. The cell lethality was increased about 30% with temperature increasing from 17 to 37°C. The myocardium tissue temperature increase was reported that less than 5°C in the case of our PD Ablation®. We think that the photocytotoxicity change by these temperature increasing would be negligible in our PD Ablation®. We suggest that the temperature maintaining would be necessary to keep the photocytotoxicity efficiency in the case of the open surgery that would cause the tissue surface temperature decreasing.

Cell diversity and network dynamics in photosensitive human brain organoids.

PubMed

Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z; Sherwood, John L; Min Yang, Sung; Berger, Daniel R; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin P; Boyden, Edward S; Lichtman, Jeff W; Williams, Ziv M; McCarroll, Steven A; Arlotta, Paola

2017-05-04

In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.

Imidazoacridinone Derivatives as Efficient Sensitizers in Photoantimicrobial Chemotherapy

PubMed Central

Taraszkiewicz, Aleksandra; Grinholc, Mariusz; Bielawski, Krzysztof P.; Kawiak, Anna

2013-01-01

The objective of this study was to investigate a new potential photosensitizer (PS) in the photodynamic inactivation (PDI) of microorganisms in vitro (11 reference strains and 13 clinical isolates, representing common Gram-positive and Gram-negative human pathogens), with special emphasis on Candida albicans. We studied the light-induced cytotoxicity of the imidazoacridinone derivative C1330 toward fungal cells grown in planktonic form. We examined the influence of various parameters (time of incubation, PDI quencher effect, and C1330 accumulation in C. albicans cells) on the efficacy of light-dependent cytotoxicity. Additionally, we checked for the potential cyto- and phototoxic activity of C1330 against human dermal keratinocytes. In our research, we used a broadband incoherent blue light source (380 to 470 nm) with an output power of 100 mW/cm2. In vitro studies showed that the C1330 action against C. albicans was a light-dependent process. C1330 was an efficient photosensitizer in the photodynamic inactivation of C. albicans, which reduced the growth of planktonic cells by 6.1 log10 units. Efficient accumulation of PS in the nucleus and vacuoles was observed after 30 min of incubation, which correlated with the highest photokilling efficacy. Significant changes in intracellular structure were observed upon illumination of C1330-incubated C. albicans cells. In the case of the human HaCaT cell line, approximately 40% of cells survived the treatment, which indicates the potential benefit of further study of the application of C1330 in photoantimicrobial chemotherapy. These data suggest that PDI may be a viable approach for the treatment of localized C. albicans infections. PMID:23563951

Silicon(IV) phthalocyanines substituted axially with different nucleoside moieties. Effects of nucleoside type on the photosensitizing efficiencies and in vitro photodynamic activities.

PubMed

Zheng, Bi-Yuan; Shen, Xiao-Min; Zhao, Dong-Mei; Cai, Yi-Bin; Ke, Mei-Rong; Huang, Jian-Dong

2016-06-01

A series of new silicon(IV) phthalocyanines (SiPcs) di-substituted axially with different nucleoside moieties have been synthesized and evaluated for their singlet oxygen quantum yields (ΦΔ) and in vitro photodynamic activities. The adenosine-substituted SiPc shows a lower photosensitizing efficiency (ΦΔ=0.35) than the uridine- and cytidine-substituted analogs (ΦΔ=0.42-0.44), while the guanosine-substituted SiPc exhibits a weakest singlet oxygen generation efficiency with a ΦΔ value down to 0.03. On the other hand, replacing axial adenosines with chloro-modified adenosines and purines can result in the increase of photogenerating singlet oxygen efficiencies of SiPcs. The formed SiPcs 1 and 2, which contain monochloro-modified adenosines and dichloro-modified purines respectively, appear as efficient photosensitizers with ΦΔ of 0.42-0.44. Both compounds 1 and 2 present high photocytotoxicities against HepG2 and BGC823 cancer cells with IC50 values ranging from 9nM to 33nM. The photocytotoxicities of these two compounds are remarkably higher than the well-known anticancer photosensitizer, chlorin e6 (IC50=752nM against HepG2 cells) in the same condition. As revealed by confocal microscopy, for both cell lines, compound 1 can essentially bind to mitochondria, while compound 2 is just partially localized in mitochondria. In addition, the two compounds induce cell death of HepG2 cells likely through apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Flexible and fragmentable tandem photosensitive nanocrystal skins

NASA Astrophysics Data System (ADS)

Akhavan, S.; Uran, C.; Bozok, B.; Gungor, K.; Kelestemur, Y.; Lesnyak, V.; Gaponik, N.; Eychmüller, A.; Demir, H. V.

2016-02-01

We proposed and demonstrated the first account of large-area, semi-transparent, tandem photosensitive nanocrystal skins (PNSs) constructed on flexible substrates operating on the principle of photogenerated potential buildup, which avoid the need for applying an external bias and circumvent the current-matching limitation between junctions. We successfully fabricated and operated the tandem PNSs composed of single monolayers of colloidal water-soluble CdTe and CdHgTe nanocrystals (NCs) in adjacent junctions on a Kapton polymer tape. Owing to the usage of a single NC layer in each junction, noise generation was significantly reduced while keeping the resulting PNS films considerably transparent. In each junction, photogenerated excitons are dissociated at the interface of the semi-transparent Al electrode and the NC layer, with holes migrating to the contact electrode and electrons trapped in the NCs. As a result, the tandem PNSs lead to an open-circuit photovoltage buildup equal to the sum of those of the two single junctions, exhibiting a total voltage buildup of 128.4 mV at an excitation intensity of 75.8 μW cm-2 at 350 nm. Furthermore, we showed that these flexible PNSs could be bent over 3.5 mm radius of curvature and cut out in arbitrary shapes without damaging the operation of individual parts and without introducing any significant loss in the total sensitivity. These findings indicate that the NC skins are promising as building blocks to make low-cost, flexible, large-area UV/visible sensing platforms with highly efficient full-spectrum conversion.We proposed and demonstrated the first account of large-area, semi-transparent, tandem photosensitive nanocrystal skins (PNSs) constructed on flexible substrates operating on the principle of photogenerated potential buildup, which avoid the need for applying an external bias and circumvent the current-matching limitation between junctions. We successfully fabricated and operated the tandem PNSs composed of

A Novel Photosensitizer 3¹,13¹-phenylhydrazine -Mppa (BPHM) and Its in Vitro Photodynamic Therapy against HeLa Cells.

PubMed

Li, Wenting; Tan, Guanghui; Cheng, Jianjun; Zhao, Lishuang; Wang, Zhiqiang; Jin, Yingxue

2016-04-29

Photodynamic therapy (PDT) has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa) has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-3¹,13¹ bisphenylhydrazone modified methyl pyropheophorbide-a (BPHM) was designed and synthesized with the consideration that phenylhydrazone structure may extend absorption wavelength of methyl pyro-pheophorbide-a (Mppa), and make the photosensitizer potential in deep tumor treatment. The synthesis, spectral properties and in vitro photodynamic therapy (PDT) against human HeLa cervical cancer cell line was studied. Methyl thiazolyl tetrazolium (MTT) assay showed the title compound could achieve strong inhibition of cervical cancer cell viability under visible light (675 nm, 25 J/cm²). Cell uptake experiments were performed on HeLa cells. Morphological changes were examined and analyzed by fluorescent inverted microscope. In addition, the mechanism of the photochemical processes of PDT was investigated, which showed that the formation of singlet oxygen after treatment with PDT played a moderate important role.

Photosensitized rose Bengal-induced phototoxicity on human melanoma cell line under natural sunlight exposure.

PubMed

Srivastav, Ajeet K; Mujtaba, Syed Faiz; Dwivedi, Ashish; Amar, Saroj K; Goyal, Shruti; Verma, Ankit; Kushwaha, Hari N; Chaturvedi, Rajnish K; Ray, Ratan Singh

2016-03-01

Rose Bengal (RB) is an anionic water-soluble xanthene dye, which used for many years to assess eye cornea and conjunctiva damage. RB showed strong absorption maxima (λmax) under visible light followed by UV-B and UV-A. RB under sunlight exposure showed a time-dependent photodegradation. Our results show that photosensitized RB generates (1)O2 via Type-II photodynamic pathway and induced DNA damage under sunlight/UV-R exposure. 2'dGuO degradation, micronuclei formation, and single- and double-strand breakage were the outcome of photogenotoxicity caused by RB. Quenching studies with NaN3 advocate the involvement of (1)O2 in RB photogenotoxicity. RB induced linoleic acid photoperoxidation, which was parallel to (1)O2-mediated DNA damage. Oxidative stress in A375 cell line (human melanoma cell line) was detected through DCF-DA assay. Photosensitized RB decreased maximum cellular viability under sunlight followed by UV-B and UV-A exposures. Apoptosis was detected as a pattern of cell death through the increased of caspase-3 activity, decreased mitochondrial membrane potential, and PS translocation through inner to outer plasma membrane. Increased cytosolic levels of Bax also advocate the apoptotic cell death. We propose a p53-mediated apoptosis via increased expression of Bax gene and protein. Thus, the exact mechanism behind RB phototoxicity was the involvement of (1)O2, which induced oxidative stress-mediated DNA and membrane damage, finally apoptotic cell death under natural sunlight exposure. The study suggests that after the use of RB, sunlight exposure may avoid to prevent from its harmful effects. Copyright © 2015. Published by Elsevier B.V.

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

NASA Astrophysics Data System (ADS)

Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M.; Deng, Wei

2018-02-01

We developed light-triggered liposomes incorporating gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized by adjusting the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of HSPC: PE-NH2: gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of these liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox loaded liposomes were applied to human colorectal cancer cells, HCT116, and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity, compared to the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may have improved therapeutic efficacy in photodynamic therapy and chemotherapy.

All-Optical Micro Motors Based on Moving Gratings in Photosensitive Media

NASA Technical Reports Server (NTRS)

Curley, M.; Sarkisov, S. S.; Fields, A.; Smith, C.; Kukhtarev, N.; Kulishov, M. B.; Adamovsky, Grigory

2001-01-01

An all-optical micromotor with a rotor driven by a traveling wave of surface deformation of a stator being in contact with the rotor is being studied. Instead of an ultrasonic wave produced by an electrically driven piezoelectric actuator as in ultrasonic motors, the wave is a result of a photo-induced surface deformation of a photosensitive material produced by an incident radiation. A thin piezoelectric polymer will deform more easily LiNbO3 or metal when irradiated with light. The type of photosensitive material studied are piezoelectric polymers with and without coatings for connecting electrodes. In order to be considered as a possible candidate for micromotors, the material should exhibit surface deformation produced by a laser beam of the order of 10 microns. This is compared to the deformations produced by static holographic gratings studied in photorefractive crystals of LiNbO3 using high vertical resolution surface profilometer Dektak 3 and surface interferometer WYKO. An experimental setup showing the oscillations has been developed. The setup uses a chopped beam from an Argon ion laser to produce the deformation while a probe beam is reflected by the thin film into a fiber which is then detected on an oscilloscope. A ramp voltage signal generator will drive the piezoelectric film in another experiment to determine the resonance of the film. A current is generated when light is incident upon the film and this current can be measured. The reverse process has already been demonstrated in other piezoelectric actuators. Changing voltage, polarity, and frequency of the signal can easily generate vibrations similar to those when light is incident on the film. This can be compared to the effects of laser interaction with light absorbing fluids such as solutions of 2,9,16,23-Tetrakis(phenylthio)-29H, 31 H-phthalocyanine in chlorobenzene in capillary tubes, The possibility of using a liquid with the piezoelectric film would be a novel idea for a micromotor since

Novel fully-BODIPY functionalized cyclotetraphosphazene photosensitizers having high singlet oxygen quantum yields

NASA Astrophysics Data System (ADS)

Şenkuytu, Elif; Eçik, Esra Tanrıverdi

2017-07-01

Novel fully-BODIPY functionalized dendrimeric cyclotetraphosphazenes (FBCP 1 and 2) have been synthesized and characterized by 1H, 13C and 31P NMR spectroscopies. The photophysical and photochemical properties of FBCP 1 and 2 are investigated in dichloromethane solution. The effectiveness of singlet oxygen generation was measured for FBCP 1 and 2 by UV-Vis spectra monitoring of the solution of 1,3-diphenylisobenzofuran (DPBF), which is a well-known trapping molecule used in detection of singlet oxygen. FBCP 1 and 2 show high molar extinction coefficients in the NIR region, good singlet oxygen quantum yields and appropriate photo degradation. The data presented in the work indicate that the dendrimeric cyclotetraphosphazenes are effective singlet oxygen photosensitizers that might be used for various areas of applications such as photodynamic therapy and photocatalysis.

One- and two-photon photosensitized singlet oxygen production: characterization of aromatic ketones as sensitizer standards.

PubMed

Arnbjerg, Jacob; Paterson, Martin J; Nielsen, Christian B; Jørgensen, Mikkel; Christiansen, Ove; Ogilby, Peter R

2007-07-05

Singlet molecular oxygen, O2(a1Deltag), can be efficiently produced in a photosensitized process using either one- or two-photon irradiation. The aromatic ketone 1-phenalenone (PN) is an established one-photon singlet oxygen sensitizer with many desirable attributes for use as a standard. In the present work, photophysical properties of two other aromatic ketones, pyrene-1,6-dione (PD) and benzo[cd]pyren-5-one (BP), are reported and compared to those of PN. Both PD and BP sensitize the production of singlet oxygen with near unit quantum efficiency in a nonpolar (toluene) and a polar (acetonitrile) solvent. With their more extensive pi networks, the one-photon absorption spectra for PD and BP extend out to longer wavelengths than that for PN, thus providing increased flexibility for sensitizer excitation over the range approximately 300-520 nm. Moreover, PD and BP have much larger two-photon absorption cross sections than PN over the range 655-840 nm which, in turn, results in amounts of singlet oxygen that are readily detected in optical experiments. One- and two-photon absorption spectra of PD and BP obtained using high-level calculations model the salient features of the experimental data well. In particular, the ramifications of molecular symmetry are clearly reflected in both the experimental and calculated spectra. The use of PD and BP as standards for both the one- and two-photon photosensitized production of singlet oxygen is expected to facilitate the development of new sensitizers for application in singlet-oxygen-based imaging experiments.

Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

PubMed Central

2016-01-01

Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA–protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions. PMID:27654267

High aspect ratio patterning of photosensitive polyimide with low thermal expansion coefficient and low dielectric constant

NASA Astrophysics Data System (ADS)

Dick, Andrew R.; Bell, William K.; Luke, Brendan; Maines, Erin; Mueller, Brennen; Rawlings, Brandon; Kohl, Paul A.; Grant Willson, C.

2016-07-01

A photosensitive polyimide system based on amine catalyzed imidization of a precursor poly(amic ester) is described. The material is based on the meta ethyl ester of pyromellitic dianhydride and 2,2' bis(trifluoromethyl)benzidine. It acts as a negative tone resist when formulated with a photobase generator. The material exhibits a dielectric constant of 3.0 in the gigahertz range, a coefficient of thermal expansion of 6±2 ppm/K, and can be patterned to aspect ratios of >2 when formulated with a highly quantum efficient cinnamide type photobase generator.

Viscosity reduction of isotonic solutions of the photosensitizer TPCS2a by cyclodextrin complexation.

PubMed

Tovsen, Marianne Lilletvedt; Tho, Ingunn; Tønnesen, Hanne Hjorth

2018-02-01

Meso-tetraphenyl chlorin disulphonate (TPCS 2a ) is a photosensitizer (PS) particularly developed and patented for use in the technology of photochemical internalization (PCI) against cancer. TPCS 2a is known to aggregate in aqueous media even at low concentrations (≥0.1 µM) and to form a high-viscosity network at clinically relevant concentrations (mM). The aim of this work was to evaluate the effect of two hydroxypropylated cyclodextrin derivatives of beta and gamma type, respectively i.e. HPβCD and HPγCD, on the aggregation and solubilization of TPCS 2a in isotonic solutions. Samples containing micromolar concentrations of TPCS 2a were studied spectrophotometrically, while samples containing a clinical relevant concentration (10 mM = 9 mg/ml) of TPCS 2a were evaluated by dynamic viscosity measurements. HPβCD was determined to be a more suitable solubilizer of TPCS 2a than HPγCD in aqueous media both in the absence and presence of salt. The complexation stoichiometry between TPCS 2a /HPβCD at micromolar to millimolar concentrations of TPCS 2a was determined to be 1:3 and 1:2 in the absence and presence of isotonic NaCl, respectively. The network of TPCS 2a (10 mM) was broken down in the presence of 3% w/v (= 20 mM) HPβCD, i.e. a 1:2 molar ratio between TPCS 2a and the cyclodextrin. Formation of the inclusion complex resulted in low viscosity samples both in water and in the presence of isotonic NaCl or phosphate buffered saline (PBS) at 25 °C and 37 °C.

The Photosensitivity of Rhodopsin Bleaching and Light-Induced Increases of Fundus Reflectance in Mice Measured In Vivo With Scanning Laser Ophthalmoscopy

PubMed Central

Zhang, Pengfei; Goswami, Mayank; Zawadzki, Robert J.; Pugh, Edward N.

2016-01-01

Purpose To quantify bleaching-induced changes in fundus reflectance in the mouse retina. Methods Light reflected from the fundus of albino (Balb/c) and pigmented (C57Bl/6J) mice was measured with a multichannel scanning laser ophthalmoscopy optical coherence tomography (SLO-OCT) optical system. Serial scanning of small retinal regions was used for bleaching rhodopsin and measuring reflectance changes. Results Serial scanning generated a saturating reflectance increase centered at 501 nm with a photosensitivity of 1.4 × 10−8 per molecule μm2 in both strains, 2-fold higher than expected were irradiance at the rod outer segment base equal to that at the retinal surface. The action spectrum of the reflectance increase corresponds to the absorption spectrum of mouse rhodopsin in situ. Spectra obtained before and after bleaching were fitted with a model of fundus reflectance, quantifying contributions from loss of rhodopsin absorption with bleaching, absorption by oxygenated hemoglobin (HbO2) in the choroid (Balb/c), and absorption by melanin (C57Bl/6J). Both mouse strains exhibited light-induced broadband reflectance changes explained as bleaching-induced reflectivity increases at photoreceptor inner segment/outer segment (IS/OS) junctions and OS tips. Conclusions The elevated photosensitivity of rhodopsin bleaching in vivo is explained by waveguide condensing of light in propagation from rod inner segment (RIS) to rod outer segment (ROS). The similar photosensitivity of rhodopsin in the two strains reveals that little light backscattered from the sclera can enter the ROS. The bleaching-induced increases in reflectance at the IS/OS junctions and OS tips resemble results previously reported in human cones, but are ascribed to rods due to their 30/1 predominance over cones in mice and to the relatively minor amount of cone M-opsin in the regions scanned. PMID:27403994

Effective photosensitization-based inactivation of Gram (-) food pathogens and molds using the chlorophyllin-chitosan complex: towards photoactive edible coatings to preserve strawberries.

PubMed

Buchovec, Irina; Lukseviciute, Viktorija; Marsalka, Arunas; Reklaitis, Ignas; Luksiene, Zivile

2016-04-01

This study is focused on the novel approaches to enhance the inactivation of the Gram (-) food pathogen Salmonella enterica and harmful molds in vitro and on the surface of strawberries using the chlorophyllin-chitosan complex. Salmonella enterica (∼1 × 10(7) CFU mL(-1)) was incubated with chlorophyllin 1.5 × 10(-5) M (Chl, food additive), chitosan 0.1% (CHS, food supplement) or the chlorophyllin-chitosan complex (1.5 × 10(-5) M Chl-0.1% CHS) and illuminated with visible light (λ = 405 nm, light dose 38 J cm(-2)) in vitro. Chlorophyllin (Chl)-based photosensitization inactivated Salmonella just by 1.8 log. Chitosan (CHS) alone incubated for 2 h with Salmonella reduced viability 2.15 log, whereas photoactivated Chl-CHS diminished bacterial viability by 7 log. SEM images indicate that the Chl-CHS complex under these experimental conditions covered the entire bacterial surface. Significant cell membrane disintegration was the main lethal injury induced in Gram (-) bacteria by this treatment. Analysis of strawberry decontamination from surface-inoculated Salmonella indicated that photoactivated Chl-CHS (1.5 × 10(-5) M Chl-0.1% CHS, 30 min incubation, light dose 38 J cm(-2)) coatings diminished the pathogen population on the surface of strawberries by 2.2 log. Decontamination of strawberries from naturally distributed yeasts/molds revealed that chitosan alone reduced the population of yeasts/molds just by 0.4 log, Chl-based photosensitization just by 0.9 log, whereas photoactivated Chl-CHS coatings reduced yeasts/molds on the surface of strawberries by 1.4 log. Electron paramagnetic resonance spectroscopy confirmed that no additional photosensitization-induced free radicals have been found in the strawberry matrix. Visual quality (color, texture) of the treated strawberries was not affected either. In conclusion, photoactive Chl-CHS exhibited strong antimicrobial action against more resistant to photosensitization Gram (-) Salmonella enterica in comparison with

Indole-3-acetic acid: a potential new photosensitizer for photodynamic therapy of acne vulgaris.

PubMed

Na, Jung-Im; Kim, So-Young; Kim, Jeong-Hye; Youn, Sang-Woong; Huh, Chang-Hun; Park, Kyoung-Chan

2011-03-01

ALA (5-aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole-3-acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment. Free radical formation was measured after visible light irradiation of IAA. Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT. To evaluate the histological changes, skin biopsies were performed on nude mice skin after IAA PDT. To evaluate the clinical efficacy of IAA PDT, 14 acne patients were treated with the following IAA PDT regimen: three times each with a 15 minutes incubation period and a 2-week interval. The number of inflammatory lesions and the amount of sebum secretion were then assessed. IAA produced free radicals with green light irradiation. Importantly, IAA lost its photosensitizing ability after exposure to certain amount of light. This implies IAA PDT would not require post-procedure photo-protection. The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT. In addition, IAA PDT treated skin showed destruction of follicular ostia epithelium. Interestingly, there was no significant difference between a 4 hours and a 30 minutes incubation, which means that longer absorption time is not necessary for IAA PDT. In the clinical study, inflammatory lesions and sebum secretion were significantly reduced. The procedure was painless and no adverse effect was observed. Photo-protection was not performed and there were no further phototoxic responses. IAA PDT has therapeutic effects on acne via its antimicrobial activities, its sebum-reducing effect and through relieving follicular occlusion. It is a very simple and safe treatment option for acne. Copyright © 2011 Wiley-Liss, Inc.

Biomcompatible gold nanorods conjugated with photosensitizers assisted for photostability and photodestructive ability

NASA Astrophysics Data System (ADS)

Kuo, Wen-Shuo; Chen, Shean-Jen

2012-02-01

Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PDT and PTT proved to be efficiently killing cancer cells as compared to PDT or PTT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability.

Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

NASA Astrophysics Data System (ADS)

Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

1996-04-01

Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

Photosensitizing Electron Transfer Processes of Fullerenes, Carbon Nanotubes, and Carbon Nanohorns.

PubMed

Ito, Osamu

2017-03-01

In this account, studies on the photosensitizing electron transfer of nanocarbons, such as fullerenes, single-walled carbon nanotubes (SWCNTs), and carbon nanohorns (CNH), performed in our laboratory for about 15 years in the early 21st century have been briefly reviewed. These novel nanocarbons act as excellent electron acceptors, when they are linked to light-absorbing electron donors, such as porphyrins or phthalocyanines. For such molecule-nanocarbon hybrids, the direct confirmation of fast, transient, electron-transfer phenomena must be performed with time-resolved spectroscopic methods, such as transient absorption spectral measurements, in addition to fluorescence time-profile measurements in the wide-wavelength regions. Careful use of these methods affords useful information to understand photoinduced electron-transfer mechanisms. In addition, kinetic data obtained by these methods can assist in the construction of light-active devices, such as photovoltaic cells and solar H 2 -generation systems. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigation of the photosensitivity of LiNbO3:BaFeO3 crystal

NASA Astrophysics Data System (ADS)

Darwish, Abdalla M.; Koplitz, Brent D.; Jackson, E.; Jalbout, F.; Jalbout, A.; Aggarwal, Mohan D.

2002-01-01

Ferromagnetic resonance (FMR) absorptions from six fine particle-samples of barium ferrite were studied over a temperature range of -195 degree(s)C to 500 degree(s)C. It was found that the shape of the FMR absorption signal is affected by the particle shape and crystalline anisotropy of each sample. From this analysis, the first magnetic anisotropy constant K1 was estimated approximately as a function of temperature. The estimation suggested that the value of K1 was sensitive to the condition of preparation of fine powders. In addition the photosensitivity of the LiNbO3:BaFe doped crystal was enhanced, suggesting the importance of Barium Ferrite powder as a potential candidate with NOL materials.

Arrays of Regenerated Fiber Bragg Gratings in Non-Hydrogen-Loaded Photosensitive Fibers for High-Temperature Sensor Networks

PubMed Central

Lindner, Eric; Chojetztki, Christoph; Brueckner, Sven; Becker, Martin; Rothhardt, Manfred; Vlekken, Johan; Bartelt, Hartmut

2009-01-01

We report about the possibility of using regenerated fiber Bragg gratings generated in photosensitive fibers without applying hydrogen loading for high temperature sensor networks. We use a thermally induced regenerative process which leads to a secondary increase in grating reflectivity. This refractive index modification has shown to become more stable after the regeneration up to temperatures of 600 °C. With the use of an interferometric writing technique, it is possible also to generate arrays of regenerated fiber Bragg gratings for sensor networks. PMID:22408510

Model studies on the photosensitized isomerization of bixin.

PubMed

Montenegro, Mariana A; Rios, Alessandro de O; Mercadante, Adriana Z; Nazareno, Mónica A; Borsarelli, Claudio D

2004-01-28

The photosensitized isomerization reaction of the natural cis carotenoid bixin (methyl hydrogen 9'-cis-6, 6'-diapocarotene-6, 6'-dioate) with rose bengal or methylene blue as the sensitizer in acetonitrile/methanol (1:1) solution was studied using UV-vis spectroscopy, high-performance liquid chromatography (HPLC), and time-resolved spectroscopic techniques, such as laser-flash photolysis and singlet oxygen phosphorescence detection. In both N(2)- and air-saturated solutions, the main product formed was all-trans-bixin. The observed isomerization rate constants, k(obs), decreased in the presence of air or with increase in the bixin concentration, suggesting the participation of the excited triplet state of bixin, (3)Bix, as precursor of the cis--> trans process. On the other hand, bixin solutions in the absence of sensitizer and/or light did not degrade, indicating that the ground state of bixin is stable to thermal isomerization at room temperature. Time-resolved spectroscopic experiments confirmed the formation of the excited triplet state of bixin and its deactivation by ground state bixin and molecular oxygen quenching processes. The primary isomerization products only degraded in the presence of air and under prolonged illumination conditions, probably due to the formation of oxidation products by reaction with singlet molecular oxygen. An energy-transfer mechanism was used to explain the observed results for the bixin transformations, and the consequences for food color are discussed.

Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum*

PubMed Central

Ramos, Rogério Rodrigo; Kozusny-Andreani, Dora Inês; Fernandes, Adjaci Uchôa; Baptista, Mauricio da Silva

2016-01-01

BACKGROUND Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring. PMID:27192510

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity.

PubMed

Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M; Deng, Wei

2017-01-01

We developed light-triggered liposomes incorporating 3-5 nm hydrophobic gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized for varying the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl- sn -glycero-3-phosphoethanolamine- N -(hexanoylamine):gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy.

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

PubMed Central

Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M; Deng, Wei

2017-01-01

We developed light-triggered liposomes incorporating 3–5 nm hydrophobic gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized for varying the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(hexanoylamine):gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy. PMID:28203076

Efficient photodynamic therapy against gram-positive and gram-negative bacteria using THPTS, a cationic photosensitizer excited by infrared wavelength.

PubMed

Schastak, Stanislaw; Ziganshyna, Svitlana; Gitter, Burkhard; Wiedemann, Peter; Claudepierre, Thomas

2010-07-20

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to kill antibiotic-resistant bacteria uses light in combination with a photosensitizer to induce a phototoxic reaction. Concentrations of 1, 10 and 100microM of tetrahydroporphyrin-tetratosylat (THPTS) and different incubation times (30, 90 and 180min) were used to measure photodynamic efficiency against two Gram-positive strains of S.aureus (MSSA and MRSA), and two Gram-negative strains of E.coli and P.aeruginosa. We found that phototoxicity of the drug is independent of the antibiotic resistance pattern when incubated in PBS for the investigated strains. Also, an incubation with 100microM THPTS followed by illumination, yielded a 6lg (> or =99.999%) decrease in the viable numbers of all bacteria strains tested, indicating that the THPTS drug has a high degree of photodynamic inactivation. We then modulated incubation time, photosensitizer concentration and monitored the effect of serum on the THPTS activity. In doing so, we established the conditions to obtain the strongest bactericidal effect. Our results suggest that this new and highly pure synthetic compound should improve the efficiency of photodynamic therapy against multiresistant bacteria and has a significant potential for clinical applications in the treatment of nosocomial infections.

Photodynamic therapy with two different photosensitizers as a supplement to instrumentation/irrigation procedures in promoting intracanal reduction of Enterococcus faecalis.

PubMed

Souza, Letícia C; Brito, Patrícia R R; de Oliveira, Julio C Machado; Alves, Flávio R F; Moreira, Edson J L; Sampaio-Filho, Hélio R; Rôças, Isabela N; Siqueira, José F

2010-02-01

This in vitro study aimed to investigate the antibacterial effects of photodynamic therapy (PDT) with methylene blue (MB) or toluidine blue (TB) (both at 15 microg/mL) as a supplement to instrumentation/irrigation of root canals experimentally contaminated with Enterococcus faecalis. Seventy extracted teeth had their root canals contaminated with an endodontic strain of E. faecalis for 7 days, instrumented with nickel-titanium instruments and irrigated either with 2.5% NaOCl or with 0.85% NaCl, and then randomly distributed into four experimental groups: MB/NaOCl (PDT with MB and NaOCl as the irrigant), TB/NaOCl (PDT with TB and NaOCl as the irrigant), MB/NaCl (PDT with MB and NaCl as the irrigant), and TB/NaCl (PDT with TB and NaCl as the irrigant). For PDT, the photosensitizer remained in the canal for 2 minutes before exposed to red light emitted from a diode laser for 4 minutes. Samples were taken before and after instrumentation/irrigation and following the specific PDT procedure for each group, plated onto Mitis-salivarius agar and the colony forming units counted. Regardless of the irrigant used (NaOCl or NaCl), instrumentation significantly reduced bacterial counts in comparison to the baseline (p < 0.001). NaOCl as the irrigant was significantly more effective than NaCl, and this difference persisted after PDT, irrespective of the photosensitizer used (p < 0.05). PDT with either MB or TB did not significantly enhance disinfection after chemomechanical preparation using NaOCl as irrigant (p > 0.05). No significant differences were observed between the two photosensitizers (p > 0.05). These in vitro results suggest that PDT with either MB or TB may not exert a significant supplemental effect to instrumentation/irrigation procedures with regard to intracanal disinfection. Further adjustments in the PDT protocol may be required to enhance predictability in bacterial elimination before clinical use is recommended. Copyright 2010 American Association of

Lethal photosensitization of wound-associated microbes using indocyanine green and near-infrared light.

PubMed

Omar, Ghada S; Wilson, Michael; Nair, Sean P

2008-07-01

The increase in resistance to antibiotics among disease-causing bacteria necessitates the development of alternative antimicrobial approaches such as the use of light-activated antimicrobial agents (LAAAs). Light of an appropriate wavelength activates the LAAA to produce cytotoxic species which can then cause bacterial cell death via loss of membrane integrity, lipid peroxidation, the inactivation of essential enzymes, and/or exertion of mutagenic effects due to DNA modification. In this study, the effect of the LAAA indocyanine green excited with high or low intensity light (808 nm) from a near-infrared laser (NIR) on the viability of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa was investigated. All species were susceptible to killing by the LAAA, the bactericidal effect being dependent on both the concentration of indocyanine green and the light dose. Indocyanine green photosensitization using both high (1.37 W cm(-2)) and low (0.048 W cm(-2)) intensity NIR laser light was able to achieve reductions of 5.6 log10 (>99.99%) and 6.8 log10 (>99.99%) in the viable counts of Staph. aureus and Strep. pyogenes (using starting concentrations of 106-107 CFU ml(-1)). Kills of 99.99% were obtained for P. aeruginosa (initial concentration 108-109 CFU ml(-1)) photosensitized by the high intensity light (1.37 W cm(-2)); while a kill of 80% was achieved using low intensity irradiation (0.07 W cm(-2)). The effects of L-tryptophan (a singlet oxygen scavenger) and deuterium oxide (as an enhancer of the life span of singlet oxygen) on the survival of Staph. aureus was also studied. L-tryptophan reduced the proportion of Staph. aureus killed; whereas deuterium oxide increased the proportion killed suggesting that singlet oxygen was involved in the killing of the bacteria. These findings imply that indocyanine green in combination with light from a near-infrared laser may be an effective means of eradicating bacteria from wounds and burns.

Photosensitive adhesive bonding process of magnetooptic waveguides with Si guiding layer for optical nonreciprocal devices

NASA Astrophysics Data System (ADS)

Choowitsakunlert, Salinee; Takagiwa, Kenji; Kobashigawa, Takuya; Hosoya, Nariaki; Silapunt, Rardchawadee; Yokoi, Hideki

2018-05-01

A photosensitive adhesive bonding process for a magnetooptic waveguide for an optical isolator employing a nonreciprocal guided-radiation mode conversion is investigated at 1.55 µm. The magnetooptic waveguide is a straight rib type, and it is fabricated by bonding the Si guiding layer to a magnetic garnet. In the fabrication process, an adhesive material is diluted to obtain a certain thickness before depositing on a silicon-on-insulator (SOI) substrate. The relationship between the percent dilution ratio and the thickness of the adhesive layer is considered. The smallest gap thickness is found to be 0.66 µm at a dilution ratio of 2%.

Dosimetry of UV radiation with special respect to presence of photosensitizers or other chemical agents

NASA Astrophysics Data System (ADS)

Ronto, Gyorgyi; Csik, Gabriella; Gaspar, S.

1994-02-01

A method has been developed for measuring the biologically effective dose (BED) of solar radiation. The method applies phage T7 as a biosensor in a monitoring system. The work presents a series of dose measurements caused by direct and global irradiation. Comparisons are made of the results obtained in the same time in different places in Hungary in 1992 and 1993. A doubling of the measured BED was found which can not be explained with the ozone depletion only. An interpretation of phage T7 dose as well as transformation of the results into MED are presented. The influence of the photosensitization as an additive damage is discussed as well.

Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

PubMed

Haupt, Sara; Malik, Zvi; Ehrenberg, Benjamin

2014-01-01

Photodynamic therapy (PDT) of cancer involves inflicting lethal damage to the cells of malignant tumors, primarily by singlet oxygen that is generated following light-absorption in a photosensitizer molecule. Dysfunction of cells is manifested in many ways, including peroxidation of cellular components, membrane rupture, depolarization of electric potentials, termination of mitochondrial activity, onset of apoptosis and necrosis and eventually cell lysis. These events do not necessarily occur in linear fashion and different types of damage to cell components occur, most probably, in parallel. In this report we measured the relative rates of damage to two cellular membranes: the plasma membrane and the mitochondrial membrane. We employed photosensitizers of diverse hydrophobicities and used different incubation procedures, which lead to their different intra-cellular localizations. We monitored the damage that was inflicted on these membranes, by employing optical probes of membrane integrity, in a multi-color FACS experiment. The potentiometric indicator JC-1 monitored the electric cross-membrane potential of the mitochondria and the fluorometric indicator Draq7 monitored the rupture of the plasma membrane. We show that the electric depolarization of the mitochondrial membrane and the damage to the enveloping plasma membrane proceed with different kinetics that reflect the molecular character and intracellular location of the sensitizer: PpIX that is synthesized in the cells from ALA causes rapid mitochondrial damage and very slow damage to the plasma membrane, while externally added PpIX has an opposite effect. The hydrophilic sensitizer HypS4 can be taken up by the cells by different incubation conditions, and these affect its intracellular location, and as a consequence either the plasma membrane or the mitochondria is damaged first. A similar correlation was found for additional extracellularly-provided photosensitizers HP and PpIX.

Controlled Vectorial Electron Transfer and Photoelectrochemical Applications of Layered Relay/Photosensitizer-Imprinted Au Nanoparticle Architectures on Electrodes.

PubMed

Metzger, Tzuriel S; Tel-Vered, Ran; Willner, Itamar

2016-03-23

Two configurations of molecularly imprinted bis-aniline-bridged Au nanoparticles (NPs) for the specific binding of the electron acceptor N,N'-dimethyl-4,4'-bipyridinium (MV(2+) ) and for the photosensitizer Zn(II)-protoporphyrin IX (Zn(II)-PP-IX) are assembled on electrodes, and the photoelectrochemical features of the two configurations are discussed. Configuration I includes the MV(2+) -imprinted Au NPs matrix as a base layer, on which the Zn(II)-PP-IX-imprinted Au NPs layer is deposited, while configuration II consists of a bilayer corresponding to the reversed imprinting order. Irradiation of the two electrodes in the presence of a benzoquinone/benzohydroquinone redox probe yields photocurrents of unique features: (i) Whereas configuration I yields an anodic photocurrent, the photocurrent generated by configuration II is cathodic. (ii) The photocurrents obtained upon irradiation of the imprinted electrodes are substantially higher as compared to the nonimprinted surfaces. The high photocurrents generated by the imprinted Au NPs-modified electrodes are attributed to the effective loading of the imprinted matrices with the MV(2+) and Zn(II)-PP-IX units and to the effective charge separation proceeding in the systems. The directional anodic/cathodic photocurrents are rationalized in terms of vectorial electron transfer processes dictated by the imprinting order and by the redox potentials of the photosensitizer/electron acceptor units associated with the imprinted sites in the two configurations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-photon polymerization technique for microfabrication of CAD-designed 3D scaffolds from commercially available photosensitive materials.

PubMed

Ovsianikov, Aleksandr; Schlie, Sabrina; Ngezahayo, Anaclet; Haverich, Axel; Chichkov, Boris N

2007-01-01

We report on recent advances in the fabrication of three-dimensional (3D) scaffolds for tissue engineering and regenerative medicine constructs using a two-photon polymerization technique (2PP). 2PP is a novel CAD/CAM technology allowing the fabrication of any computer-designed 3D structure from a photosensitive polymeric material. The flexibility of this technology and the ability to precisely define 3D construct geometry allows issues associated with vascularization and patient-specific tissue fabrication to be directly addressed. The fabrication of reproducible scaffold structures by 2PP is important for systematic studies of cellular processes and better understanding of in vitro tissue formation. In this study, 2PP was applied for the generation of 3D scaffold-like structures, using the photosensitive organic-inorganic hybrid polymer ORMOCER (ORganically MOdified CERamics) and epoxy-based SU8 materials. By comparing the proliferation rates of cells grown on flat material surfaces and under control conditions, it was demonstrated that ORMOCER and SU8 are not cytotoxic. Additional tests show that the DNA strand breaking of GFSHR-17 granulosa cells was not affected by the presence of ORMOCER. Furthermore, gap junction conductance measurements revealed that ORMOCER did not alter the formation of cell-cell junctions, critical for functional tissue growth. The possibilities of seeding 3D structures with cells were analysed. These studies demonstrate the great potential of 2PP technique for the manufacturing of scaffolds with controlled topology and properties.

Silane and germane plasma diagnostics for depositing photosensitive a-SiGe:H films

NASA Technical Reports Server (NTRS)

Shing, Y. H.; Perry, J. W.; Allevato, C. E.

1988-01-01

Highly photosensitive a-SiGe:H films with a light-to-dark conductivity ratio of 8 x 103 and an optical bandgap of 1.40 eV have been produced by RF glow discharge using hydrogen dilution of SiH4 and GeH4 mixed gas plasma. The critical role of hydrogen dilution in GeH4 containing plasmas is to suppress the gas-phase polymerization and promote the incorporation of Ge into the film. It is observed that inelastic laser light scattering of the RF plasma is a sensitive method for monitoring the onset of the gas-phase polymerization. In situ coherent anti-Stokes Raman spectroscopy measurements have shown that the dissociation rate of GeH4 is a factor of three larger than that of SiH4.

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

PubMed Central

Wielaender, Franziska; Sarviaho, Riika; James, Fiona; Hytönen, Marjo K.; Cortez, Miguel A.; Kluger, Gerhard; Koskinen, Lotta L. E.; Arumilli, Meharji; Kornberg, Marion; Bathen-Noethen, Andrea; Tipold, Andrea; Rentmeister, Kai; Bhatti, Sofie F. M.; Hülsmeyer, Velia; Boettcher, Irene C.; Tästensen, Carina; Flegel, Thomas; Leeb, Tosso; Matiasek, Kaspar; Fischer, Andrea; Lohi, Hannes

2017-01-01

The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization. PMID:28223533

Inclusion of 5-[4-(1-dodecanoylpyridinium)]-10,15,20-triphenylporphine in supramolecular aggregates of cationic amphiphilic cyclodextrins: physicochemical characterization of the complexes and strengthening of the antimicrobial photosensitizing activity.

PubMed

Ferro, Stefania; Jori, Giulio; Sortino, Salvatore; Stancanelli, Rosanna; Nikolov, Peter; Tognon, Giuseppe; Ricchelli, Fernanda; Mazzaglia, Antonino

2009-09-14

Recent findings suggest that visible light-promoted photooxidative processes mediated by sensitizers of appropriate chemical structure could represent a useful tool for properly addressing the problem of the increasing occurrence of infectious diseases caused by multiantibiotic-resistant microbial pathogens. The monocationic meso-substituted porphyrin 5-[4-(1-dodecanoylpyridinium)]-10,15,20-triphenyl-porphine (TDPyP) complexed into supramolecular aggregates of cationic amphiphilic beta-cyclodextrin (SC(6)NH(2)) (mean diameter = 20 nm) appeared to be endowed with favorable properties to act as a photosensitizing agent, including a very high quantum yield (Phi(Delta) = 0.90) for the generation of the highly reactive oxygen species, singlet oxygen ((1)O(2)). Although the yield of (1)O(2) generation was comparable to that obtained after TDPyP incorporation into cationic unilamellar liposomes of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP) SC(6)NH(2)-bound TDPyP was more active than DOTAP-bound TDPyP in photosensitizing the inactivation of the Gram-positive methicillin-resistant bacterium Staphylococcus aureus (MRSA). At variance with DOTAP-bound TDPyP, photoactivated SC(6)NH(2)-bound TDPyP was efficient also in photokilling Gram-negative bacterial pathogens, such as Escherichia coli . These observations are in agreement with the well-known photobactericidal effect of positively charged porphyrin derivatives, which can be markedly enhanced after incorporation into carriers with multiple positive charges. In addition, transmission electron microscopy studies revealed that potentiation of the TDPyP-mediated photobactericidal effect by incorporation into SC(6)NH(2) is a consequence of the carrier's ability to promote an efficient crossing of the very tightly organized three-dimensional architecture of the bacterial outer wall by the embedded porphyrin so that a prompt interaction between the short-lived photogenerated (1)O(2) and the nearby

Photodynamic inactivation of Listeria innocua biofilms with food-grade photosensitizers: a curcumin-rich extract of Curcuma longa vs commercial curcumin.

PubMed

Bonifácio, D; Martins, C; David, B; Lemos, C; Neves, M G P M S; Almeida, A; Pinto, D C G A; Faustino, M A F; Cunha, Â

2018-03-22

The aim of this work is to assess the potential of curcumin in the photosensitization of biofilms of Listeria. Biofilms of Listeria innocua, were irradiated with blue light in the presence of a curcumin-rich extract of Curcuma longa or commercial curcumin. Similar experiments were conducted with planktonic cells, for comparison. A reduction of 4·9 log in the concentration of viable biofilm cells was obtained with 3·7 mg l -1 of commercial curcumin. Planktonic cells were much more susceptible (6·1 log reduction). A tetracationic porphyrin, used as a reference photosensitizer (PS), caused a very modest inactivation of the biofilm (1·1 log) and complete inactivation of the planktonic form (>8 log). Curcumin is an effective PS for the photodynamic control of Listeria biofilms and the inactivation efficiency attained with this natural compound is higher than with the porphyrin. This result may point to a better performance of type I PSs against bacterial biofilms by circumventing the limitations to singlet-oxygen diffusion imposed by the extracellular matrix. Curcumin represents a promising alternative to the control of bacteria and bacterial biofilms in food products particularly in the case of meat products in which turmeric is used as spice. © 2018 The Society for Applied Microbiology.

Solid state synthesis of chitosan and its unsaturated derivatives for laser microfabrication of 3D scaffolds

NASA Astrophysics Data System (ADS)

Akopova, T. A.; Demina, T. S.; Bagratashvili, V. N.; Bardakova, K. N.; Novikov, M. M.; Selezneva, I. I.; Istomin, A. V.; Svidchenko, E. A.; Cherkaev, G. V.; Surin, N. M.; Timashev, P. S.

2015-07-01

Chitosans with various degrees of deacetylation and molecular weights and their allyl substituted derivatives were obtained through a solvent-free reaction under shear deformation in an extruder. Structure and physical-chemical analysis of the samples were carried out using nuclear magnetic resonance (NMR), ultraviolet (UV) and infrared radiation (IR) spectroscopy. Photosensitive materials based on the synthesized polymers were successfully used for microfabrication of 3D well-defined architectonic structures by laser stereolithography. Study on the metabolic activity of NCTC L929 cultured in the presence of the cured chitosan extracts indicates that the engineered biomaterials could support adhesion, spreading and growth of adherent-dependent cells, and thus could be considered as biocompatible scaffolds.

Encapsulation efficacy of natural and synthetic photosensitizers by silica nanoparticles for photodynamic applications.

PubMed

Makhadmeh, Ghaseb Naser; Abdul Aziz, Azlan; Abdul Razak, Khairunisak; Abu Noqta, Osama

2015-12-01

This study analysed the physical effects of Cichorium Pumilum (CP), as a natural photosensitizer (PS), and Protoporphyrin IX (PpIX), as a synthetic PS, encapsulated with silica nanoparticles (SiNPs) in photodynamic therapy. The optimum concentrations of CP and PpIX, needed to destroy Red Blood Cells (RBC), were determined and the efficacy of encapsulated CP and PpIX were compared with naked CP and PpIX was verified. The results confirmed the applicability of CP and PpIX encapsulated in SiNPs on RBCs, and established a relationship between the encapsulated CP and PpIX concentration and the time required to rupture 50% of the RBCs (t50). The CP and PpIX encapsulated in SiNPs exhibited higher efficacy compared with that of naked CP and PpIX, respectively, and CP had less efficacy compared with PpIX.

In vitro and in vivo photosensitized inactivation of dermatophyte fungi by heterotricyclic dyes.

PubMed Central

Propst, C; Lubin, L

1978-01-01

The ability of three heterotricyclic dyes to photosensitize dermatophyte fungi was studied with Trichophyton mentagrophytes and Microsporum gypseum. In vitro studies showed that methylene blue, neutral red, and proflavine were capable of killing these fungi when used in conjunction with broad-spectrum light. Proflavine, however, killed both fungi most rapidly and was used for further studies. Fungal killing by proflavine plus light was dependent on dye concentration, pH, light wavelength, and light intensity. Based on the in vitro studies, a treatment regimen was developed for in vivo use on experimentally infected animals. When treatment of guinea pigs inoculated with T. mentagrophytes was begun during fungal invasion, lesion formation at inoculated sites was either prevented or substantially reduced. When treatment was begun after lesion formation, however, light-plus-dyed treated sites showed only slightly faster curing than untreated sites. PMID:669788

Masked red-emitting carbopyronine dyes with photosensitive 2-diazo-1-indanone caging group.

PubMed

Kolmakov, Kirill; Wurm, Christian; Sednev, Maksim V; Bossi, Mariano L; Belov, Vladimir N; Hell, Stefan W

2012-03-01

Caged near-IR emitting fluorescent dyes are in high demand in optical microscopy but up to now were unavailable. We discovered that the combination of a carbopyronine dye core and a photosensitive 2-diazo-1-indanone residue leads to masked near-IR emitting fluorescent dyes. Illumination of these caged dyes with either UV or visible light (λ < 420 nm) efficiently generates fluorescent compounds with absorption and emission at 635 nm and 660 nm, respectively. A high-yielding synthetic route with attractive possibilities for further dye design is described in detail. Good photostability, high contrast, and a large fluorescence quantum yield after uncaging are the most important features of the new compounds for non-invasive imaging in high-resolution optical microscopy. For use in immunolabelling the caged dyes were decorated with a (hydrophilic) linker and an (activated) carboxyl group.

A new near infrared photosensitizing nanoplatform containing blue-emitting up-conversion nanoparticles and hypocrellin A for photodynamic therapy of cancer cells

NASA Astrophysics Data System (ADS)

Jin, Shan; Zhou, Liangjun; Gu, Zhanjun; Tian, Gan; Yan, Liang; Ren, Wenlu; Yin, Wenyan; Liu, Xiaodong; Zhang, Xiao; Hu, Zhongbo; Zhao, Yuliang

2013-11-01

The utilization of up-conversion nanoparticles (UCNPs) for photodynamic therapy (PDT) has gained significant interest due to their unique ability to convert near infrared light to UV/visible light. Previous work mainly focused on the fabrication of green and red emitting UCNPs to load photosensitizers (PSs) for PDT. In this work, we firstly developed a new multifunctional nanoplatform combining blue-emitting UCNPs with blue-light excited PS (hypocrellin A, HA) as a NIR photosensitizing nanoplatform for PDT of cancer cells. Tween 20 coated NaYbF4:Tm, Gd@NaGdF4 UCNPs (Tween 20-UCNPs) with strong blue up-conversion luminescence and good water dispersibility were prepared for use as PS carriers. The blue emission band matched well with the efficient absorption band of HA, thereby facilitating the resonance energy transfer from UCNPs to HA and then activating HA to produce singlet oxygen (1O2). The in vitro study showed that these Tween 20-UCNPs@HA complexes could efficiently produce 1O2 to kill cancer cells under 980 nm NIR excitation. Moreover, these Gd3+ and Yb3+ containing nanoparticles also exhibited positive contrast effects in both T1 weighted magnetic resonance imaging (MRI) and computed tomography (CT) imaging, making them become a multifunctional platform for simultaneous PDT and bio-imaging.The utilization of up-conversion nanoparticles (UCNPs) for photodynamic therapy (PDT) has gained significant interest due to their unique ability to convert near infrared light to UV/visible light. Previous work mainly focused on the fabrication of green and red emitting UCNPs to load photosensitizers (PSs) for PDT. In this work, we firstly developed a new multifunctional nanoplatform combining blue-emitting UCNPs with blue-light excited PS (hypocrellin A, HA) as a NIR photosensitizing nanoplatform for PDT of cancer cells. Tween 20 coated NaYbF4:Tm, Gd@NaGdF4 UCNPs (Tween 20-UCNPs) with strong blue up-conversion luminescence and good water dispersibility were prepared for

Molecular orbital evaluation of charge flow dynamics in natural pigments based photosensitizers.

PubMed

Heera, Thekinneydath Rajan; Cindrella, Louis

2010-03-01

The relationship between structure and photo electrochemical property of ten natural pigments from plants, insects and microbes has been analyzed using density functional theory (DFT) at the B3LYP/6-31G(d) level. The essential parameters for their photoelectrochemical behaviour such as ground state geometries, electronic transition energies and oxidation potentials are computed. The attachment tendency of the anchoring groups, expressed as the deprotonation order, is determined by calculating the proton affinities at different sites of the molecules. A thorough analysis of the charge flow dynamics in the molecular orbitals (HOMO and LUMO) of these molecules has been carried out and presented to emphasize the role of these orbitals in effective charge separation, the important feature of photosensitizers for DSSC. This study highlights that the flexible spatial orientation provided by the bridging aliphatic unsaturation favours the oscillator strength and the hydroxyl anchor group attached to the ring of delocalized pi electron cloud acts as the effective anchor.

Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

NASA Astrophysics Data System (ADS)

Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

2015-01-01

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

PubMed Central

Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.

2015-01-01

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to un-targeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging. PMID:25519743

Phosphorus dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer-photosensitizer complexes: Cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue.

PubMed

Dabrzalska, Monika; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

2015-08-15

Dendrimers due to their unique architecture may play an important role in drug delivery systems including chemotherapy, gene therapy and recently, photodynamic therapy as well. We investigated two dendrimer-photosensitizer systems in context of potential use of these systems in photodynamic therapy. The mixtures of an anionic phosphorus dendrimer of the second generation and methylene blue were studied by UV-vis spectroscopy while that of a cationic phosphorus dendrimer (third generation) and rose bengal were investigated by spectrofluorimetric methods. Spectroscopic analysis of these two systems revealed the formation of dendrimer-photosensitizer complexes via electrostatic interactions as well as π stacking. The stoichiometry of the rose bengal-cationic dendrimer complex was estimated to be 7:1 and 9:1 for the methylene blue-anionic dendrimer complex. The results suggest that these polyanionic or polycationic phosphorus dendrimers can be promising candidates as carriers in photodynamic therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Combined Benzoporphyrin Derivative Monoacid Ring A Photodynamic Therapy and Pulsed Dye Laser for Port Wine Stain Birthmarks

PubMed Central

Tournas, Joshua A.; Lai, Jennifer; Truitt, Anne; Huang, Y.C.; Osann, Kathryn E.; Choi, Bernard; Kelly, Kristen M.

2009-01-01

Background Pulsed dye laser (PDL) is a commonly utilized treatment for port wine stain birthmarks (PWS) in the United States; however, results are variable and few patients achieve complete removal. Photodynamic therapy (PDT) is commonly used in China, but treatment associated photosensitivity lasts several weeks and scarring may occur. We propose an alternative treatment option, combined PDT+PDL and performed a proof-of-concept preliminary clinical trial. Methods Subjects with non-facial PWS were studied. Each subject had four test sites: control, PDL alone, PDT alone (benzoporphyrin derivative monoacid ring A photosensitizer with 576 nm light), and PDT+PDL. Radiant exposure time for PDT was increased in increments of 15 J/cm2. Authors evaluated photographs and chromametric measurements before and 12 weeks post-treatment. Results No serious adverse events were reported; epidermal changes were mild and self-limited. No clinical blanching was noted in control or PDT-alone sites. At PDT radiant exposures of 15 and 30 J/cm2, equivalent purpura and blanching was observed at PDL and PDT+PDL sites. At PDT radiant exposures over 30 J/cm2, greater purpura was noted at PDT+PDL sites as compared to PDL alone. Starting at 75 J/cm2, improved blanching was noted at PDT+PDL sites. Conclusions Preliminary results indicate that PDT+PDL is safe and may offer improved PWS treatment efficacy. Additional studies are warranted. PMID:19932451

Effect of gallium-arsenic laser on photosensitized periodontopathic anaerobic organisms: An in vitro study

PubMed Central

Mathur, Setu; Kothiwale, Shaila Veerappa; Nag, Buddhi Prakash; Mathur, Tanu; Bhansali, Ashoka; Khatri, Rohit Kumar

2016-01-01

Background: The mainstay of periodontal therapy is mechanical removal of subgingival plaque. There is considerable interest in supplementing it with the use of antibiotics and antiseptics. Many drawbacks are associated with these adjunctive pharmacological regimens such as development of resistance to antibiotics and disruption of microflora of the gastrointestinal tract. Hence, alternate means of killing subgingival bacteria are clearly desirable. One such method is the use of laser. Aim: This study aimed to investigate antibacterial capabilities of gallium-arsenic (Ga-As) laser on photosensitized periodontopathic organisms. The three bacteria selected for the study were Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia. Settings: The subjects for the study were selected from the patients visiting the Department of Periodontics, Karnataka Lingayat Education Society's Institute of Dental Sciences, Belgaum. Design: In vitro study design. Materials and Methods: Subgingival plaque samples collected from chronic periodontitis patients were cultured anaerobically for 72 h. Predetermined number of colonies of each bacterium was taken and was then divided into cases and control groups. Both groups were photosensitized using toluidine blue O (TBO) dye and the case groups were irradiated with Ga-As laser. Bacterial colonies were then serially diluted and were incubated for subculture. After incubation period, the number of viable bacterial count was performed. Statistical Analysis: Wilcoxon-signed rank test was carried out to determine significance of reduction on subsequent dilution within the bacterial group. Mann–Whitney U-test was performed to determine the significance of reduction between cases and control of particular bacterial group. Results: The results revealed substantial reduction in the viable bacterial count. F. nucleatum was found to be most sensitive to killing by laser irradiation followed by P. intermedia and then P

Overcoming Multidrug Resistance via Photodestruction of ABCG2-Rich Extracellular Vesicles Sequestering Photosensitive Chemotherapeutics

PubMed Central

Goler-Baron, Vicky; Assaraf, Yehuda G.

2012-01-01

Multidrug resistance (MDR) remains a dominant impediment to curative cancer chemotherapy. Efflux transporters of the ATP-binding cassette (ABC) superfamily including ABCG2, ABCB1 and ABCC1 mediate MDR to multiple structurally and functionally distinct antitumor agents. Recently we identified a novel mechanism of MDR in which ABCG2-rich extracellular vesicles (EVs) form in between attached neighbor breast cancer cells and highly concentrate various chemotherapeutics in an ABCG2-dependent manner, thereby sequestering them away from their intracellular targets. Hence, development of novel strategies to overcome MDR modalities is a major goal of cancer research. Towards this end, we here developed a novel approach to selectively target and kill MDR cancer cells. We show that illumination of EVs that accumulated photosensitive cytotoxic drugs including imidazoacridinones (IAs) and topotecan resulted in intravesicular formation of reactive oxygen species (ROS) and severe damage to the EVs membrane that is shared by EVs-forming cells, thereby leading to tumor cell lysis and the overcoming of MDR. Furthermore, consistent with the weak base nature of IAs, MDR cells that are devoid of EVs but contained an increased number of lysosomes, highly accumulated IAs in lysosomes and upon photosensitization were efficiently killed via ROS-dependent lysosomal rupture. Combining targeted lysis of IAs-loaded EVs and lysosomes elicited a synergistic cytotoxic effect resulting in MDR reversal. In contrast, topotecan, a bona fide transport substrate of ABCG2, accumulated exclusively in EVs of MDR cells but was neither detected in lysosomes of normal breast epithelial cells nor in non-MDR breast cancer cells. This exclusive accumulation in EVs enhanced the selectivity of the cytotoxic effect exerted by photodynamic therapy to MDR cells without harming normal cells. Moreover, lysosomal alkalinization with bafilomycin A1 abrogated lysosomal accumulation of IAs, consequently preventing

Radical production from photosensitization of imidazoles

NASA Astrophysics Data System (ADS)

Corral Arroyo, P.; Gonzalez, L.; Steimer, S.; Aellig, R.; Volkamer, R. M.; George, C.; Bartels-Rausch, T.; Ammann, M.

2015-12-01

Reactions promoted by light are key in atmospheric chemistry. Some of them occur in the condensed phase of aerosols containing light absorbing organic compounds (George et al., 2015). This work explores the radical reactions initiated by near-UV light in mixtures of citric acid (CA) and imidazole-2-carboxaldehyde (IC) using NO as a probe molecule for HO2, by means of coated wall flow tube experiments. Citric acid may act as H atom or electron donor in condensed phase radical cycles. IC may act as a photosensitizer. The loss of NO was measured by a chemiluminescence detector. The dependence of the NO loss on the NO concentration, the IC/CA ratio in the film, relative humidity, light intensity, oxygen molar fraction were investigated as well as the HONO and NO2 yields. We also added halide salts to investigate the effect of a competing electron donor in the system and the output of halogens to the gas phase. We found a correlation between the loss of NO above the film and the molar ratio of IC/CA and the light intensity. The variation of the NO loss with oxygen corroborates a mechanism, in which the triplet excited state of IC is reduced by citric acid, to a reduced ketyl radical that transfers an electron to molecular oxygen, which in turn leads to production of HO2 radicals. Therefore, the NO loss in the gas phase is related to the production of HO2 radicals. Relative humidity had a strong impact on the HO2 output, which shows a maximum production rate at around 30%. The addition of halide ions (X- = Cl-, Br-, I-) increases the HO2 output at low concentration and decrease it at higher concentration when X2- radical ions likely scavenge HO2. We could preliminarily quantify for the first time the contribution of these processes to the oxidative capacity in the atmosphere and conclude that their role is significant for aerosol aging and potentially a significant source of halogen compounds to the gas phase.

Photodynamic treatment with phenothiazinium photosensitizers kills both ungerminated and germinated microconidia of the pathogenic fungi Fusarium oxysporum, Fusarium moniliforme and Fusarium solani.

PubMed

de Menezes, Henrique Dantas; Tonani, Ludmilla; Bachmann, Luciano; Wainwright, Mark; Braga, Gilberto Úbida Leite; von Zeska Kress, Marcia Regina

2016-11-01

The search for alternatives to control microorganisms is necessary both in clinical and agricultural areas. Antimicrobial photodynamic treatment (APDT) is a promising light-based approach that can be used to control both human and plant pathogenic fungi. In the present study, we evaluated the effects of photodynamic treatment with red light and four phenothiazinium photosensitizers (PS): methylene blue (MB), toluidine blue O (TBO), new methylene blue N (NMBN) and the phenothiazinium derivative S137 on ungerminated and germinated microconidia of Fusarium oxysporum, F. moniliforme, and F. solani. APDT with each PS killed efficiently both the quiescent ungerminated microconidia and metabolically active germinated microconidia of the three Fusarium species. Washing away the unbound PS from the microconidia (both ungerminated and germinated) before red light exposure reduced but did not prevent the effect of APDT. Subcelullar localization of PS in ungerminated and germinated microconidia and the effects of photodynamic treatment on cell membranes were also evaluated in the three Fusarium species. APDT with MB, TBO, NMBN or S137 increased the membrane permeability in microconidia and APDT with NMBN or S137 increased the lipids peroxidation in microconidia of the three Fusarium species. These findings expand the understanding of photodynamic inactivation of filamentous fungi with phenothiazinium PS. Copyright © 2016 Elsevier B.V. All rights reserved.

Hepatic photosensitization in buffaloes intoxicated by Brachiaria decumbens in Minas Gerais state, Brazil.

PubMed

De Oliveira, C H S; Barbosa, J D; Oliveira, C M C; Bastianetto, E; Melo, M M; Haraguchi, M; Freitas, L G L; Silva, M X; Leite, R C

2013-10-01

The aim of this paper is to report the study of hepatogenous photosensitization in buffaloes during two outbreaks provoked by ingestion of Brachiaria decumbens in Minas Gerais state, Brazil. Ten young buffaloes in outbreak 1 and seven buffaloes in outbreak 2 were intoxicated by B. decumbens. Nine clinically healthy buffaloes raised under the same conditions as the sick animals served as the control group. All animals were subjected to clinical examination, and serum was collected to measure gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), direct bilirubin (DB), indirect bilirubin (IB) and total bilirubin (TB) as indicators of liver function and urea and creatinine as indicators of renal function. Histopathology of liver fragments from five different animals was carried out. During the outbreaks and every two months for one year, samples of grass from paddocks where the animals got sick were collected for quantitative evaluation of the saponin protodioscin, combined with observations of pasture characteristics and daily rainfall. Clinical signs included apathy, weight loss, restlessness, scar retraction of the ears and intense itching at the skin lesions, mainly on the rump, the tail head, neck and hindlimbs, similar to the signs observed in other ruminants. Only the GGT enzyme presented significantly different (P < 0.01) serum levels between intoxicated animals (n = 17) and healthy animals (n = 9), indicating liver damage in buffaloes bred in B. decumbens pastures. Microscopy of the liver showed foamy macrophages and lesions of liver disease associated with the presence of crystals in the bile ducts, which have also been found in sheep and cattle poisoned by grasses of the genus Brachiaria. During the outbreaks, protodioscin levels were higher than 3%, and shortly after, these levels were reduced to less than 0.80%, suggesting a hepatic injury etiology. The outbreaks took place at the beginning of the rainy season, and there was a positive

Enhanced photocatalytic hydrogen production from an MCM-41-immobilized photosensitizer-[Fe-Fe] hydrogenase mimic dyad.

PubMed

Wang, Wen; Yu, Tianjun; Zeng, Yi; Chen, Jinping; Yang, Guoqiang; Li, Yi

2014-11-01

A covalently linked photosensitizer-catalytic center dyad Ps-Hy, consisting of two bis(2-phenylpyridine)(2,2'-bipyridine)iridium(iii) chromophores (Ps) and a diiron hydrogenase mimic (Hy) was constructed by using click reaction. Ps-Hy was incorporated into K(+)-exchanged molecular sieve MCM-41 to form a composite (Ps-Hy@MCM-41), which has been successfully applied to the photochemical production of hydrogen. The catalytic activity of Ps-Hy@MCM-41 is ∼3-fold higher as compared with that of Ps-Hy in the absence of MCM-41. The incorporation of Ps-Hy into MCM-41 stabilizes the catalyst, and consequently, advances the photocatalysis. The present study provides a potential strategy for improving catalytic efficiency of artificial photosynthesis systems using mesoporous molecular sieves.

Analysis of photogem (hematoporphyrin derivative) and blood interaction

NASA Astrophysics Data System (ADS)

Corrêa, Thaila Quatrini; Pratavieira, Sebastião.; Bagnato, Vanderlei Salvador

2017-07-01

Sepsis is a potentially fatal condition that occurs when an infectious agent, such as bacteria, gets in a person's bloodstream. The infection affects the immune system, which then triggers a reaction that can cause uncontrolled inflammation in the body1 . All blood components may present the contamination. Once inoculated bacteria in a blood component, it can proliferate rapidly reaching high levels within few hours and, in a short period, it may lead to several basal changes in the individual and even death2 . Studies have shown an increase in the incidence of sepsis over the years, and it is mainly due to the growing resistance of microorganisms to antibiotics since these drugs are still sold and used improperly3 . The photodynamic inactivation (PDI) has been one of the most promising alternatives for microbiological control and other diseases. Its principle of action is based on a photosensitizer (PS) activated by light at the correct wavelength to oxidize organic substrates, resulting in cytotoxic effects4,5. The technique is being applied to a large variety of microorganisms and decontaminating blood. Some studies have investigated the action of PDI in blood6-9, and even then, there is a need to understand better what happens when we apply PS and light in blood in an attempt to eliminate the microorganisms. Photogem is a hematoporphyrin derivative that has been used with success in many clinical cases such as skin cancer and inactivation of bacteria10,11. Previous studies have shown that PDI using Photogem as a photosensitizing molecule is a good alternative for blood decontamination12,13. In the previous studies were observed hemolysis when red blood cells (RBCs) were submitted to PS concentration and light dose tested. This study has been conducted to further understand through absorption spectroscopy and fluorescence confocal microscope the PS-blood interaction. This is important because the PDI damage needs to be restricted to the bacteria and the blood

Time-resolved singlet oxygen luminescence detection under photodynamic therapy relevant conditions: comparison of ex vivo application of two photosensitizer formulations

NASA Astrophysics Data System (ADS)

Schlothauer, Jan C.; Hackbarth, Steffen; Jäger, Lutz; Drobniewski, Kai; Patel, Hemantbhai; Gorun, Sergiu M.; Röder, Beate

2012-11-01

Singlet oxygen plays a crucial role in photo-dermatology and photodynamic therapy (PDT) of cancer. Its direct observation by measuring the phosphorescence at 1270 nm, however, is still challenging due to the very low emission probability. It is especially challenging for the time-resolved detection of singlet oxygen kinetics in vivo which is of special interest for biomedical applications. Photosensitized generation of singlet oxygen, in pig ear skin as model for human skin, is investigated here. Two photosensitizers (PS) were topically applied to the pig ear skin and examined in a comparative study, which include the amphiphilic pheophorbide-a and the highly hydrophobic perfluoroalkylated zinc phthalocyanine (F64PcZn). Fluorescence microscopy indicates the exclusive accumulation of pheophorbide-a in the stratum corneum, while F64PcZn can also accumulate in deeper layers of the epidermis of the pig ear skin. The kinetics obtained with phosphorescence measurements show the singlet oxygen interaction with the PS microenvironment. Different generation sites of singlet oxygen correlate with the luminescence kinetics. The results show that singlet oxygen luminescence detection can be used as a diagnostic tool, not only for research, but also during treatment. The detection methodology is suitable for the monitoring of chemical quenchers' oxidation as well as O2 saturation at singlet oxygen concentration levels relevant to PDT treatment protocols.

Mechanistic investigation of doxycycline photosensitization by picosecond-pulsed and continuous wave laser irradiation of cells in culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shea, C.R.; Hefetz, Y.; Gillies, R.

1990-04-15

In order to elucidate the photophysical mechanisms of cellular phototoxicity sensitized by doxycycline, MGH-U1 human bladder carcinoma cells in vitro were treated with 20.7 microM doxycycline and irradiated with either a pulsed (lambda = 355 nm, pulse duration = 24 ps) or a continuous wave (lambda = 351 nm) laser. Cumulative radiant exposure and irradiance were systematically varied in experiments with both lasers. Phototoxicity was assessed by epifluorescence microscopy of unfixed cells using rhodamine 123 labeling of mitochondria. With the continuous wave source, the cumulative radiant exposure required for induction of phototoxic injury was independent of irradiance. With the 24-ps-pulsedmore » source, a significantly lower cumulative radiant exposure was required to induce the phototoxicity when the peak irradiance was 5.8 x 10(7) or 1.3 x 10(8) watts cm-2 compared with when peak irradiance was either lower (6.0 x 10(6) watts cm-2) or higher (7.6 x 10(8) watts cm-2). The measured fluorescence lifetimes of doxycycline in buffered saline solution were longer than the laser pulse duration of 24 ps. The increased efficiency of photosensitization at the optimal peak irradiance in the ps domain appears to result from sequential multiphoton absorption involving higher excited states of the singlet manifold. At the highest irradiance studied, on the other hand, reduced efficiency of photosensitization is attributed to increased photodegradation of doxycycline from higher excited states by processes such as photoionization. A model consistent with these observations is presented along with calculations, based on simple rate equations, that fit the essentials of the proposed model.« less

Singlet Oxygen Generation by UVA Light Exposure of Endogenous Photosensitizers

PubMed Central

Baier, Jürgen; Maisch, Tim; Maier, Max; Engel, Eva; Landthaler, Michael; Bäumler, Wolfgang

2006-01-01

UVA light (320–400 nm) has been shown to produce deleterious biological effects in tissue due to the generation of singlet oxygen by substances like flavins or urocanic acid. Riboflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), β-nicotinamide adenine dinucleotide (NAD), and β-nicotinamide adenine dinucleotide phosphate (NADP), urocanic acid, or cholesterol in solution were excited at 355 nm. Singlet oxygen was directly detected by time-resolved measurement of its luminescence at 1270 nm. NAD, NADP, and cholesterol showed no luminescence signal possibly due to the very low absorption coefficient at 355 nm. Singlet oxygen luminescence of urocanic acid was clearly detected but the signal was too weak to quantify a quantum yield. The quantum yield of singlet oxygen was precisely determined for riboflavin (ΦΔ = 0.54 ± 0.07), FMN (ΦΔ = 0.51 ± 0.07), and FAD (ΦΔ = 0.07 ± 0.02). In aerated solution, riboflavin and FMN generate more singlet oxygen than exogenous photosensitizers such as Photofrin, which are applied in photodynamic therapy to kill cancer cells. With decreasing oxygen concentration, the quantum yield of singlet oxygen generation decreased, which must be considered when assessing the role of singlet oxygen at low oxygen concentrations (inside tissue). PMID:16751234

X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield.

PubMed

Clement, Sandhya; Deng, Wei; Camilleri, Elizabeth; Wilson, Brian C; Goldys, Ewa M

2016-01-28

Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF3 nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8 keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79 ± 0.05 for the conjugate with 31 verteporfin molecules per CeF3 nanoparticle, the highest conjugation level used. From this result we estimate the singlet oxygen dose generated from CeF3-verteporfin conjugates for a therapeutic dose of 60 Gy of ionizing radiation at energies of 6 MeV and 30 keV to be (1.2 ± 0.7) × 10(8) and (2.0 ± 0.1) × 10(9) singlet oxygen molecules per cell, respectively. These are comparable with cytotoxic doses of 5 × 10(7)-2 × 10(9) singlet oxygen molecules per cell reported in the literature for photodynamic therapy using light activation. We confirmed that the CeF3-VP conjugates enhanced cell killing with 6 MeV radiation. This work confirms the feasibility of using X- or γ- ray activated nanoparticle-photosensitizer conjugates, either to supplement the radiation treatment of cancer, or as an independent treatment modality.

Structural Factors and Mechanisms Underlying the Improved Photodynamic Cell Killing with Silicon Phthalocyanine Photosensitizers Directed to Lysosomes Versus Mitochondria

PubMed Central

Rodriguez, Myriam E.; Zhang, Ping; Azizuddin, Kashif; Delos Santos, Grace B.; Chiu, Song-mao; Xue, Liang-yan; Berlin, Jeffery C.; Peng, Xinzhan; Wu, Hongqiao; Lam, Minh; Nieminen, Anna-Liisa; Kenney, Malcolm E.; Oleinick, Nancy L.

2012-01-01

The phthalocyanine photosensitizer Pc 4 has been shown to bind preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, especially Bcl-2, are photodamaged and apoptosis, as indicated by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase, is triggered. A series of analogs of Pc 4 were synthesized, and the results demonstrate that Pcs with the aminopropylsiloxy ligand of Pc 4 or a similar one on one side of the Pc ring and a second large axial ligand on the other side of the ring have unexpected properties, including enhanced cell uptake, greater monomerization resulting in greater intracellular fluorescence and three-fold higher affinity constants for liposomes. The hydroxyl-bearing axial ligands tend to reduce aggregation of the Pc and direct it to lysosomes, resulting in four to six times more killing of cells, as defined by loss of clonogenicity, than with Pc 4. Whereas Pc 4-PDT photodamages Bcl-2 and Bcl-xL, Pc 181-PDT causes much less photodamage to Bcl-2 over the same dose–response range relative to cell killing, with earlier cleavage of Bid and slower caspase-3-dependent apoptosis. Therefore, within this series of photosensitizers, these hydroxyl-bearing axial ligands are less aggregated than is Pc 4, tend to localize to lysosomes and are more effective in overall cell killing than is Pc 4, but induce apoptosis more slowly and by a modified pathway. PMID:19508642

Photodynamic effect of photosensitizer-loaded hollow silica nanoparticles for hepatobiliary malignancies: an in vitro and in vivo study

NASA Astrophysics Data System (ADS)

Deng, Xiaofeng; Xiong, Li; Wen, Yu; Liu, Zhongtao; Pei, Dongni; Huang, Yaxun; Miao, Xiongying

2014-03-01

Background and aims: Nanoparticles have been explored recently as an efficient delivery system for photosensitizers in photodynamic therapy. In this study, polyhematoporphyrin (C34H38N4NaO5,) was loaded into hollow silica nanoparticles (HSNP) by one-step wet chemical-based synthetic route. We evaluate the efficacy and safety of polyhematoporphyrin-loaded HSNP with hepatobiliary malignant cells and in vivo models. Methods: Human liver cancer, cholangiocarcinoma and gallbladder cancer cells were cultured with the HSNP and cellular viability was determined by MTT assay. Apoptotic and necrotic cells were measured by flow cytometry. Finally, we investigate its effect in vivo. Results: In MTT assay, the cell viability of QBC939, Huh-7, GBC-SD and HepG2 cells of the HSNP was 6.4+/-1.3%, 6.5+/-1.2%, 3.7+/-1.2% and 4.7+/-2.0%, respectively, which were significant different from that of free polyhematoporphyrin 62.4+/-4.7%, 62.5+/-6.0%, 33.4+/-6.5% and 44.3+/-1.9%. Flow cytometry demonstrated the laser-induced cell death with polyhematoporphyrin-loaded HSNP was much more severe. Similarly, in vivo results of each kind of cell revealed 14 days post-photoradiated, tumor sizes of the HSNP group were significantly smaller. Administration of the HSNP without illumination cannot cause killing effect both in vitro and in vivo experiments. Conclusions: HSNP is a desirable delivery system in photodynamic therapy for hepatobiliary malignacies, with improved aqueous solubility, stability and transport efficiency of photosensitizers.

Photosensitized Reduction of Carbon Dioxide in Solution Using Noble-Metal Clusters for Electron Transfer

NASA Astrophysics Data System (ADS)

Toshima, Naoki; Yamaji, Yumi; Teranishi, Toshiharu; Yonezawa, Tetsu

1995-03-01

Carbon dioxide was reduced to methane by visible-light irradiation of a solution composed of tris(bipyridine)ruthenium(III) as photosensitizer, ethylenediaminetetraacetic acid disodium salt as sacrificial reagent, methyl viologen as electron relay, and a colloidal dispersion of polymer-protected noble-metal clusters, prepared by alcohol-reduction, as catalyst. Among the noble-metal clusters examined, Pt clusters showed the highest activity for the formation of methane as well as hydrogen. In order to improve the activity, oxidized clusters and bimetallic clusters were also applied. For example, the CH4 yield in 3-h irradiation increased from 51 x 10-3 μmol with unoxidized Pt clusters to 72 x 10-3 μmol with partially oxidized ones. In the case of Pt/Ru bimetalic systems, the improvement of the catalytic activity by air treatment was much greater than in case of monometallic clusters.

In vitro phototoxic potential and photochemical properties of imidazopyridine derivative: a novel 5-HT4 partial agonist.

PubMed

Onoue, Satomi; Igarashi, Naoko; Yamauchi, Yukinori; Kojima, Takashi; Murase, Noriaki; Zhou, Yu; Yamada, Shizuo; Tsuda, Yoshiko

2008-10-01

Drug-induced phototoxic skin responses have been recognized as undesirable side effects, and as we previously proposed the determination of reactive oxygen species (ROS) from photo-irradiated compounds can be effective for the prediction of phototoxic potential. In this investigation, we evaluated the photosensitizing properties of imidazopyridine derivative, a novel 5-HT(4) partial agonist, using ROS assay and several analytical/biochemical techniques. Exposure of the compound to simulated sunlight resulted in the significant production of singlet oxygen, which is indicative of its phototoxic potential. In practice, an imidazopyridine derivative under UVA/B light exposure also showed significant photodegradation and even photobiochemical events; peroxidation of fatty acid and genetic damage after DNA-binding, which are considered as causative agents for phototoxic dermatitis. Interestingly, both photodegradation and lipoperoxidation were dramatically attenuated by the addition of radical scavengers, especially singlet oxygen quenchers, suggesting the possible involvement of ROS generation in the phototoxic pathways. In the 3T3 neutral red uptake phototoxicity test, imidazopyridine derivative also showed the phototoxic effect on 3T3 mouse fibroblast cells. These results suggest the phototoxic risk of newly synthesized imidazopyridine derivative and also verify the usefulness of ROS assay for phototoxicity prediction. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Controlled growth of larger heterojunction interface area for organic photosensitive devices

DOEpatents

Yang, Fan [Somerset, NJ; Forrest, Stephen R [Ann Arbor, MI

2009-12-29

An optoelectronic device and a method of fabricating a photosensitive optoelectronic device includes depositing a first organic semiconductor material on a first electrode to form a continuous first layer having protrusions, a side of the first layer opposite the first electrode having a surface area at least three times greater than an underlying lateral cross-sectional area; depositing a second organic semiconductor material directly on the first layer to form a discontinuous second layer, portions of the first layer remaining exposed; depositing a third organic semiconductor material directly on the second layer to form a discontinuous third layer, portions of at least the second layer remaining exposed; depositing a fourth organic semiconductor material on the third layer to form a continuous fourth layer, filling any exposed gaps and recesses in the first, second, and third layers; and depositing a second electrode on the fourth layer, wherein at least one of the first electrode and the second electrode is transparent, and the first and third organic semiconductor materials are both of a donor-type or an acceptor-type relative to second and fourth organic semiconductor materials, which are of the other material type.

Inactivation of bacteria via photosensitization of vitamin K3 by UV-A light.

PubMed

Xu, Fei; Vostal, Jaroslav G

2014-09-01

This study investigated inactivation of bacteria with ultraviolet light A irradiation in combination with vitamin K3 as a photosensitizer. Six bacteria including Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, and Escherichia coli suspended in vitamin K3 aqueous solution were exposed to ultraviolet light A. Five of six bacteria, with the exception of Pseudomonas aeruginosa, were reduced by eight logs with 1600 μM of vitamin K3 and 5.8 J cm(-2) UV-A irradiation. Pseudomonas aeruginosa was reduced by four logs under these conditions. Reactive oxygen species including singlet oxygen, hydroxyl radical and superoxide anion radical were generated in vitamin K3 aqueous solution under UV-A irradiation. These results suggest that vitamin K3 and UV-A irradiation may be effective for bacterial inactivation in environmental and medical applications. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Photosensitivity study of GeS2 chalcogenide glass under femtosecond laser pulses irradiation

NASA Astrophysics Data System (ADS)

Ayiriveetil, Arunbabu; Sabapathy, Tamilarasan; Kar, Ajoy K.; Asokan, Sundarrajan

2015-07-01

The present study discusses the photosensitivity of GeS2 chalcogenide glass in response to irradiation with femtosecond pulses at 1047 nm. Bulk GeS2 glasses are prepared by conventional melt quenching technique and the amorphous nature of the glass is confirmed using X-ray diffraction. Ultrafast laser inscription technique is used to fabricate the straight channel waveguides in the glass. Single scan and multi scan waveguides are inscribed in GeS2 glasses of length 0.65 cm using a master oscillator power amplifier Yb doped fiber laser (IMRA μjewel D400) with different pulse energy and translation speed. Diameters of the inscribed waveguides are measured and its dependence on the inscription parameters such as translation speed and pulse energy is studied. Butt coupling method is used to characterize the loss measurement of the inscribed optical waveguides. The mode field image of the waveguides is captured using CCD camera and compared with the mode field image of a standard SMF-28 fibers.

Photosensitized electron transfer processes in SiO2 colloids and sodium lauryl sulfate micellar systems: Correlation of quantum yields with interfacial surface potentials

PubMed Central

Laane, Colja; Willner, Itamar; Otvos, John W.; Calvin, Melvin

1981-01-01

The effectiveness of negatively charged colloidal SiO2 particles in controlling photosensitized electron transfer reactions has been studied and compared with that of the negatively charged sodium lauryl sulfate (NaLauSO4) micellar system. In particular, the photosensitized reduction of the zwitterionic electron acceptor propylviologen sulfonate (PVS0) with tris(2,2′-bipyridinium)ruthenium(II) [Ru(bipy)32+] as the sensitizer and triethanolamine as the electron donor is found to have a quantum yield of 0.033 for formation of the radical anion (PVS[unk]) in the SiO2 colloid compared with 0.005 in the homogeneous system and 0.0086 in a NaLauSO4 micellar solution. The higher quantum yields obtained with the SiO2 colloidal system are attributed to substantial stabilization against back reaction of the intermediate photoproducts—i.e., Ru(bipy)33+ and PVS[unk]—by electrostatic repulsion of the reduced electron acceptor from the negatively charged particle surface. The binding properties of the SiO2 particles and NaLauSO4 micelles were investigated by flow dialysis. The results show that the sensitizer binds to both interfaces and that the SiO2 interface is characterized by a much higher surface potential than the micellar interface (≈-170 mV vs. -85 mV). The effect of ionic strength on the surface potential was estimated from the Gouy-Chapman theory, and the measured quantum yields of photosensitized electron transfer were correlated with surface potential at different ionic strengths. This correlation shows that the quantum yield is not affected by surface potentials smaller than ≈-40 mV. At larger potentials, the quantum yield increases rapidly. The quantum yield obtained in the micellar system at different strengths fits nicely on the correlation curve for the colloid SiO2 system. These results indicate that the surface potential is the dominant factor in the quantum yield improvement for PVS0 reduction. PMID:16593095

High-sensitivity stress sensor based on Bragg grating in BDK-doped photosensitive polymer optical fiber

NASA Astrophysics Data System (ADS)

Wang, Tongxin; Luo, Yanhua; Peng, Gang-Ding; Zhang, Qijin

2012-02-01

Bragg grating in a single-mode photosensitive polymer optical fiber (POF) with benzil dimethyl ketal (BDK)-doped in core has been inscribed through the Sagnac ring interference method. The Bragg wavelength of grating is about 1570nm. The stress and strain response of fiber Bragg grating (FBG) has been studied respectively. By fitting the experimental result, the strain sensitivity of FBG in POF has been found to be almost same to that of conventional silica fiber Bragg gratings. However, the stress sensitivity of FBG in POF is measured to be 421pm/MPa, which is 28 times higher than FBG in silica fiber. And such high stress sensitivity makes Bragg grating in a single-mode BDK-doped POF appear to be very attractive for constructing stress sensor with high resolution.

High-temperature sustainability of strong fiber Bragg gratings written into Sb-Ge-codoped photosensitive fiber: decay mechanisms involved during annealing.

PubMed

Shen, Yonghang; He, Jinglei; Sun, Tong; Grattan, Kenneth T V

2004-03-15

An antimony--germanium- (Sb--Ge-) codoped fiber specially designed for the fabrication of fiber Bragg gratings (FBGs) with high temperature sustainability has been developed. The photosensitivity and the high-temperature sustainability of FBGs that have been written into this fiber were tested. The results obtained showed that the FBG written into this fiber has a very high temperature sustainability of 900 degrees C. A decay mechanism that involves cation hopping is presented to explain the observed high temperature sustainability of the grating written into this fiber.

Versatile digital micromirror device-based method for the recording of multilevel optical diffractive elements in photosensitive chalcogenide layers (AMTIR-1).

PubMed

Joerg, Alexandre; Vignaux, Mael; Lumeau, Julien

2016-08-01

A new alternative and versatile method for the production of diffractive optical elements (DOEs) with up to four phase levels in AMTIR-1 (Ge₃₃As₁₂Se₅₅) layers is demonstrated. The developed method proposes the use of the photosensitive properties of the layers and a specific in situ optical monitoring coupled with a reverse engineering algorithm to control the trigger points of the writing of the different diffractive patterns. Examples of various volume DOEs are presented.

Biodistribution detection of Photofrin porfimer sodium and benzoporphyrin derivative using a fiber optic sensor and ratio fluorometry

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; Papazoglou, Theodore G.; Papaioannou, Thanassis; Stavridi, Marigo; Pergadia, Vani R.; Fishbein, Michael C.; van der Veen, Maurits J.; Thomas, Reem; Grundfest, Warren S.

1994-03-01

Laser induced fluorescence spectroscopy (LIFS) was used to detect the presence of PHOTOFRINR porfimer sodium and Benzoporphyrin derivative-monoacid, ring A (BPD-MA) in various tissues. Lobund Wistar rats (n equals 49) inoculated with rat prostatic adenocarcinoma (PA-III) were injected with PHOTOFRINR porfimer sodium (7.5 - 0.25 mg/kg) and BPD (0.50 - 25 mg/kg) intravenously. A Helium-Cadmium laser (442 nm) was used as an excitation source. Our study showed that the amount of PHOTOFRINR porfimer sodium and BPD-MA which localizes in the metastatic lymph nodes is higher than in tumor and all other healthy tissues. Laser induced fluorescence spectroscopy may be a feasible method to detect the distribution of photosensitizers or other fluorescent compounds in vivo.

Explicit macroscopic singlet oxygen modeling for benzoporphyrin derivative monoacid ring A (BPD)-mediated photodynamic therapy.

PubMed

Kim, Michele M; Penjweini, Rozhin; Liang, Xing; Zhu, Timothy C

2016-11-01

Photodynamic therapy (PDT) is an effective non-ionizing treatment modality that is currently being used for various malignant and non-malignant diseases. In type II PDT with photosensitizers such as benzoporphyrin monoacid ring A (BPD), cell death is based on the creation of singlet oxygen ( 1 O 2 ). With a previously proposed empirical five-parameter macroscopic model, the threshold dose of singlet oxygen ([ 1 O 2 ] rx,sh ]) to cause tissue necrosis in tumors treated with PDT was determined along with a range of the magnitude of the relevant photochemical parameters: the photochemical oxygen consumption rate per light fluence rate and photosensitizer concentration (ξ), the probability ratio of 1 O 2 to react with ground state photosensitizer compared to a cellular target (σ), the ratio of the monomolecular decay rate of the triplet state photosensitizer (β), the low photosensitizer concentration correction factor (δ), and the macroscopic maximum oxygen supply rate (g). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated interstitially with a linear light source at 690nm with total energy released per unit length of 22.5-135J/cm and source power per unit length of 12-150mW/cm to induce different radii of necrosis. A fitting algorithm was developed to determine the photochemical parameters by minimizing the error function involving the range between the calculated reacted singlet oxygen ([ 1 O 2 ] rx ) at necrosis radius and the [ 1 O 2 ] rx,sh . [ 1 O 2 ] rx was calculated based on explicit dosimetry of the light fluence distribution, the tissue optical properties, and the BPD concentration. The initial ground state oxygen concentration ([ 3 O 2 ] 0 ) was set to be 40μM in this study. The photochemical parameters were found to be ξ=(55±40)×10 -3 cm 2 mW -1 s -1 , σ=(1.8±3)×10 -5 μM -1 , and g=1.7±0.7μMs -1 . We have taken the literature values for δ=33μM, and β=11.9μM. [ 1 O 2 ] rx has shown promise to be a more effective

From non-covalent binding to irreversible DNA lesions: nile blue and nile red as photosensitizing agents

PubMed Central

Gattuso, Hugo; Besancenot, Vanessa; Grandemange, Stéphanie; Marazzi, Marco; Monari, Antonio

2016-01-01

We report a molecular modeling study, coupled with spectroscopy experiments, on the behavior of two well known organic dyes, nile blue and nile red, when interacting with B-DNA. In particular, we evidence the presence of two competitive binding modes, for both drugs. However their subsequent photophysical behavior is different and only nile blue is able to induce DNA photosensitization via an electron transfer mechanism. Most notably, even in the case of nile blue, its sensitization capabilities strongly depend on the environment resulting in a single active binding mode: the minor groove. Fluorescence spectroscopy confirms the presence of competitive interaction modes for both sensitizers, while the sensitization via electron transfer, is possible only in the case of nile blue. PMID:27329409

Thick photosensitive polyimide film side wall angle variability and scum improvement for IC packaging stress control

NASA Astrophysics Data System (ADS)

Mehta, Sohan Singh; Yeung, Marco; Mirza, Fahad; Raman, Thiagarajan; Longenbach, Travis; Morgan, Justin; Duggan, Mark; Soedibyo, Rio A.; Reidy, Sean; Rabie, Mohamed; Cho, Jae Kyu; Premachandran, C. S.; Faruqui, Danish

2018-03-01

In this paper, we demonstrate photosensitive polyimide (PSPI) profile optimization to effectively reduce stress concentrations and enable PSPI as protection package-induced stress. Through detailed package simulation, we demonstrate 45% reduction in stress as the sidewall angle (SWA) of PSPI is increased from 45 to 80 degrees in Cu pillar package types. Through modulation of coating and develop multi-step baking temperature and time, as well as dose energy and post litho surface treatments, we demonstrate a method for reliably obtaining PSPI sidewall angle >75 degree. Additionally, we experimentally validate the simulation findings that PSPI sidewall angle impacts chip package interaction (CPI). Finally, we conclude this paper with PSPI material and tool qualification requirements for future technology node based on current challenges.

Higher operation temperature quadrant photon detectors of 2-11 μm wavelength radiation with large photosensitive areas

NASA Astrophysics Data System (ADS)

Pawluczyk, J.; Sosna, A.; Wojnowski, D.; Koźniewski, A.; Romanis, M.; Gawron, W.; Piotrowski, J.

2017-10-01

We report on the quadrant photon HgCdTe detectors optimized for 2-11 μm wavelength spectral range and Peltier or no cooling, and photosensitive area of a quad-cell of 1×1 to 4×4 mm. The devices are fabricated as photoconductors or multiple photovoltaic cells connected in series (PVM). The former are characterized by a relatively uniform photosensitive area. The PVM photovoltaic cells are distributed along the wafer surface, comprising a periodical stripe structure with a period of 20 μm. Within each period, there is an insensitive gap/trench < 9 μm wide between stripe mesas. The resulting spatial quantization error prevents positioning of the beam spot of size close to the period, but becomes negligible for the optimal spot size comparable to a quadrant-cell area. The photoconductors produce 1/f noise with about 10 kHz knee frequency, due to bias necessary for their operation. The PVM photodiodes are typically operated at 0 V bias, so they generate no 1/f noise and operation from DC is enabled. At 230 K, upper corner frequency of 16 to 100 MHz is obtained for photoconductor and 60 to 80 MHz for PVM, normalized detectivity D* 6×107 cm×Hz1/2/W to >1.4×108 cm×Hz1/2/W for photoconductor and >1.7×108 cm·Hz1/2/W for PVM, allowing for position control of the radiation beam with submicron accuracy at 16 MHz, 10.6 μm wavelength of pulsed radiation spot of 0.8 mm dia at the close-to-maximal input radiation power density in a range of detector linear operation.

Changes in brain peptides associated with reproduction and energy homeostasis in photosensitive and photorefractory migratory redheaded buntings.

PubMed

Surbhi; Rastogi, Ashutosh; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

2016-05-01

Present study examined the expression of brain peptides associated with the reproduction and energy homeostasis (GnRH/GnIH, NPY/VIP), and assessed their possible functional association in the photosensitive (non-breeding, pre-breeding), photostimulated (breeding) and photorefractory (post-breeding) migratory redheaded buntings (Emberiza bruniceps), using double-labeled immunohistochemistry. Particularly, we measured immunoreactive (-ir) cell numbers, per cent cell area and cell optical density (OD) in the preoptic area (GnRH-I), midbrain (GnRH-II), paraventricular nucleus (GnIH), dorsomedial hypothalamus, DMH and infundibular complex, INc (NPY and VIP), and lateral septal organ (VIP) of buntings kept under natural photoperiods at the wintering latitude (26°55'N). There was a significant seasonal difference in GnRH-I, not GnRH-II, with reduced -ir cells in the photosensitive and photorefractory buntings, and notably with increased cell OD between the refractory and non-breeding states with no increase in testis size. Also, increased cell OD of GnIH neurons in non-breeding state indicated its role in the maintenance of small testes during the post-refractory period. Overall, seasonal changes in GnRH-I and GnIH were found consistent with their suggested roles in reproductive regulation of absolute photorefractory birds. Further, there was a significant seasonal change in cell OD of NPY neurons in DMH, not the INc. In contrast, VIP immunoreactivity was seasonally altered, with a significantly higher VIP-ir cells in breeding than the pre-breeding state. Finally, close proximity between perikarya with fibres suggested functional interactions between the GnRH and GnIH, and NPY and VIP. Thus, seasonal plasticity of brain peptides is perhaps the part of neural regulation of seasonal reproduction and associated energy homeostasis in migratory songbirds. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

PubMed

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

Multiepitope HER2 targeting enhances photoimmunotherapy of HER2-overexpressing cancer cells with pyropheophorbide-a immunoconjugates.

PubMed

Savellano, Mark D; Pogue, Brian W; Hoopes, P Jack; Vitetta, Ellen S; Paulsen, Keith D

2005-07-15

Multi-targeting strategies improve the efficacy of antibody and immunotoxin therapies but have not yet been thoroughly explored for HER2-based cancer treatments. We investigated multi-epitope HER2 targeting to boost photosensitizer immunoconjugate uptake as a way of enhancing photoimmunotherapy. Photoimmunotherapy may allow targeted photodynamic destruction of malignancies and may also potentiate anticancer antibodies. However, one obstacle preventing its clinical use is the delivery of enough photosensitizer immunoconjugates to target cells. Anti-HER2 photosensitizer immunoconjugates were constructed from two monoclonal antibodies (mAb), HER50 and HER66, using a novel method originally developed to label photosensitizer immunoconjugates with the photosensitizer, benzoporphyrin derivative verteporfin. Photosensitizer immunoconjugates were labeled instead with a promising alternative photosensitizer, pyropheophorbide-a (PPa), which required only minor changes to the conjugation procedure. Uptake and phototoxicity experiments using human cancer cells were conducted with the photosensitizer immunoconjugates and, for comparison, with free PPa. SK-BR-3 and SK-OV-3 cells served as HER2-overexpressing target cells. MDA-MB-468 cells served as HER2-nonexpressing control cells. Photosensitizer immunoconjugates with PPa/mAb molar ratios up to approximately 10 specifically targeted and photodynamically killed HER2-overexpressing cells. On a per mole basis, photosensitizer immunoconjugates were less phototoxic than free PPa, but photosensitizer immunoconjugates were selective for target cells whereas free PPa was not. Multiepitope targeted photoimmunotherapy with a HER50 and HER66 photosensitizer immunoconjugate mixture was significantly more effective than single-epitope targeted photoimmunotherapy with a single anti-HER2 photosensitizer immunoconjugate, provided photosensitizer immunoconjugate binding was saturated. This study shows that multiepitope targeting enhances HER2

Investigation of photodynamic effect caused by MPPa-PDT on breast cancer Investigation of photodynamic effect caused by MPPa-PDT

NASA Astrophysics Data System (ADS)

Tian, Y. Y.; Hu, X. Y.; Leung, W. N.; Yuan, H. Q.; Zhang, L. Y.; Cui, F. A.; Tian, X.

2012-10-01

Breast cancer is the common malignant tumor, the incidence increases with age. Photodynamic therapy (PDT) is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. Pyropheophorbide-a methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. We are exploring the photodynamic effect caused by MPPa-PDT on breast cancer. The in vitro and in vivo experiments indicate that MPPa is a comparatively ideal photosensitizer which can induce apoptosis in breast cancer.

Target cell specific antibody-based photosensitizers for photodynamic therapy

NASA Astrophysics Data System (ADS)

Rosenblum, Lauren T.; Mitsunaga, Makoto; Kakareka, John W.; Morgan, Nicole Y.; Pohida, Thomas J.; Choyke, Peter L.; Kobayashi, Hisataka

2011-03-01

In photodynamic therapy (PDT), localized monochromatic light is used to activate targeted photosensitizers (PS) to induce cellular damage through the generation of cytotoxic species such as singlet oxygen. While first-generation PS passively targeted malignancies, a variety of targeting mechanisms have since been studied, including specifically activatable agents. Antibody internalization has previously been employed as a fluorescence activation system and could potentially enable similar activation of PS. TAMRA, Rhodamine-B and Rhodamine-6G were conjugated to trastuzumab (brand name Herceptin), a humanized monoclonal antibody with specificity for the human epidermal growth factor receptor 2 (HER2), to create quenched PS (Tra-TAM, Tra-RhoB, and Tra-Rho6G). Specific PDT with Tra-TAM and Tra-Rho6G, which formed covalently bound H-dimers, was demonstrated in HER2+ cells: Minimal cell death (<6%) was observed in all treatments of the HER2- cell line (BALB/3T3) and in treatments the HER2+ cell line (3T3/HER2) with light or trastuzumab only. There was significant light-induced cell death in HER2 expressing cells using Tra-TAM (3% dead without light, 20% at 50 J/cm2, 46% at 100 J/cm2) and Tra-Rho6G (5% dead without light, 22% at 50 J/cm2, 46% at 100 J/cm2). No efficacy was observed in treatment with Tra-RhoB, which was also non-specifically taken up by BALB/3T3 cells and which had weaker PS-antibody interactions (as demonstrated by visualization of protein and fluorescence on SDS-PAGE).

Low-stress photosensitive polyimide suspended membrane for improved thermal isolation performance

NASA Astrophysics Data System (ADS)

Fan, J.; Xing, R. Y.; Wu, W. J.; Liu, H. F.; Liu, J. Q.; Tu, L. C.

2017-11-01

In this paper, we introduce a method of isolating thermal conduction from silicon substrate for accommodating thermal-sensitive micro-devices. This method lies in fabrication of a low-stress photosensitive polyimide (PSPI) suspension structure which has lower thermal conductivity than silicon. First, a PSPI layer was patterned on a silicon wafer and hard baked. Then, a cavity was etched from the backside of the silicon substrate to form a membrane or a bridge-shape PSPI structure. After releasing, a slight deformation of about 20 nm was observed in the suspended structures, suggesting ultralow residual stress which is essential for accommodating micro-devices. In order to investigate the thermal isolation performance of the suspended PSPI structures, micro Pirani vacuum gauges, which are thermal-sensitive, had been fabricated on the PSPI structures. The measurement results illustrated that the Pirani gauges worked as expected in the range from 1- 470 Pa. Moreover, the results of the Pirani gauges based on the membrane and bridge structures were comparable, indicating that the commonly used bridge-shape structure for further reducing thermal conduction was unnecessary. Due to the excellent thermal isolation performance of PSPI, the suspended PSPI membrane is promising to be an outstanding candidate for thermal isolation applications.

Diffusion analysis of one photosensitizer in bovine teeth using fluorescence optical imaging

NASA Astrophysics Data System (ADS)

Montanha, S.; Pratavieira, S.; Jacomassi, D. P.; Rastelli, A. N. S.; Bagnato, V. S.

2012-01-01

Some photosensitizers (PSs) used for PACT (Antimicrobial Photodynamic Therapy) show an affinity for bacterial walls and can be photo-activated to cause the desired damage. However, on dentine bacterias may be less susceptible to PACT as a result of limited penetration of the PS. The aim of this study was to evaluate the diffusion of one PS based on hematoporphyrin on dentine structures. Twelve bovine incisors were used. Class III cavities (3 x 3 x 1mm) were prepared on the mesial or distal surfaces using a diamond bur. Photogem® solution at 1 mg/mL (10 uL for each cavity) was used. The experimental Groups were divided according to thickness of dentine remaining and etched or no-etched before the PS application. The fluorescence excitation source was a VelScope® system. For image capture a scientific CCD color camera PixelFly® was coupled to VelScope. For image acquisition and processing, a computational routine was developed at Matlab®. Fick's Law was used to obtain the average diffusion coefficient of PS. Differences were found between all Groups. The longitudinal temporal diffusion was influenced by the different times, thickness and acid etching.

Evaluation of a novel photosensitizing drug having antitumor effect for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Saito, Sachiko; Inai, Mizuho; Honda, Norihiro; Hazama, Hisanao; Kaneda, Yasufumi; Awazu, Kunio

2017-07-01

Prostate cancer is the second most frequently diagnosed cancer among men worldwide and a novel treatment for the disease is required. Replication-deficient virus particles, hemagglutinating virus of Japan envelope (HVJ-E), has cytotoxicity to cancer cells. To enhance the therapeutic effect of HVJ-E by photodynamic therapy (PDT) as a trigger of HVJ-E's anti-tumor effect, talaporfin sodium (Laserphyrin) used for PDT was encapsulated into HVJ-E to produce a novel photosensitizing drug, named Laserphyrin ®-HVJ-E, and its therapeutic effect for prostate cancer cells (PC-3) was evaluated. As the results, direct cytotoxicities of HVJ-E and Laserphyrin ®-HVJ-E for PC-3 after an administration time of 48 h were almost the same. Cell survival rates of PC-3, which were irradiated 2 h after administration of Laserphyrin ®-HVJ-E, were about 7.8%. Although further study is needed to find an optimal PDT condition, these results suggest that Laserphyrin ®-HVJ-E is useful for treatment of prostate cancer due to the combination of cytotoxicities of HVJ-E and PDT.

Porous Silicon Nanoparticle Photosensitizers for Singlet Oxygen and Their Phototoxicity Against Cancer Cells

PubMed Central

Xiao, Ling; Gu, Luo; Howell, Stephen B.; Sailor, Michael J.

2011-01-01

Porous Si nanoparticles, prepared from electrochemically etched single crystal Si wafers, function as photosensitizers to generate 1O2 in ethanol and in aqueous media. The preparation conditions for the porous Si nanoparticles were optimized to maximize (1) the yield of material; (2) its quantum yield of 1O2 production; and (3) its in vitro degradation properties. The optimal formulation was determined to consist of nanoparticles 146 ± 7 nm in diameter, with nominal pore sizes of 12 ± 4 nm. The quantum yield for 1O2 production is 0.10 ± 0.02 in ethanol and 0.17 ± 0.01 in H2O. HeLa or NIH-3T3 cells treated with 100 µg/mL porous Si nanoparticles and exposed to 60 J/cm2 white light (infrared filtered, 100 mW/cm2 for 10 min) exhibit ~ 45% cell death, while controls containing no nanoparticles show 10% or 25% cell death, respectively. The dark control experiment yields < 10% cytotoxicity for either cell type. PMID:21452822

Calculation of singlet oxygen formation from one photon absorbing photosensitizers used in PDT

NASA Astrophysics Data System (ADS)

Potasek, M.; Parilov, Evgueni; Beeson, K.

2013-03-01

Advances in biophotonic medicine require new information on photodynamic mechanisms. In photodynamic therapy (PDT), a photosensitizer (PS) is injected into the body and accumulates at higher concentrations in diseased tissue compared to normal tissue. The PS absorbs light from a light source and generates excited-state triplet states of the PS. The excited triplet states of the PS can then react with ground state molecular oxygen to form excited singlet - state oxygen or form other highly reactive species. The reactive species react with living cells, resulting in cel l death. This treatment is used in many forms of cancer including those in the prostrate, head and neck, lungs, bladder, esophagus and certain skin cancers. We developed a novel numerical method to model the photophysical and photochemical processes in the PS and the subsequent energy transfer to O2, improving the understanding of these processes at a molecular level. Our numerical method simulates light propagation and photo-physics in PS using methods that build on techniques previously developed for optical communications and nonlinear optics applications.

Photophysicochemical, calf thymus DNA binding and in vitro photocytotoxicity properties of tetra-morpholinoethoxy-substituted phthalocyanines and their water-soluble quaternized derivatives.

PubMed

Koçan, Halit; Kaya, Kerem; Özçeşmeci, İbrahim; Sesalan, B Şebnem; Göksel, Meltem; Durmuş, Mahmut; Burat, Ayfer Kalkan

2017-12-01

In this study, morpholinoethoxy-substituted metal-free (3), zinc(II) (4) and indium(III) (5) phthalocyanines were synthesized. These phthalocyanines were converted to their water-soluble quaternized derivatives (3Q-5Q) using excess methyl iodide as a quaternization agent. All these phthalocyanines (Pcs) were characterized by elemental analysis and different spectroscopic methods such as FT-IR, 1 H NMR, UV-Vis and mass spectrometry. The photophysical and photochemical properties such as fluorescence and generation of singlet oxygen were investigated for determination of these phthalocyanines as photosensitizers in photodynamic therapy (PDT) applications. The binding properties of quaternized phthalocyanines (3Q-5Q) to calf thymus DNA (CT-DNA) were investigated by UV-Vis and fluorescence spectrophotometric methods. The quenching effect of all quaternized phthalocyanines on the fluorescence intensity of SYBR Green-DNA complex was determined. The mixtures of 3Q, 4Q or 5Q and DNA solutions were used to determine the change in T m of double helix DNA with thermal denaturation profile. In addition, thermodynamic parameters considering their aggregation in buffer solution, which shows the spontaneity of the reactions between DNA and quaternized Pcs were investigated. On the other hand, in vitro phototoxicity and cytotoxicity behavior of the quaternized water-soluble phthalocyanine photosensitizers (3Q-5Q) were tested against the cervical cancer cell line named HeLa for evaluation of their suitability for treatment of cancer by PDT method. Peripherally tetra-substituted neutral and quaternized metal-free and metallophthalocyanines (MPcs) (Zn, In) bearing morpholinoethoxy groups were prepared. The binding of quaternized compounds (3Q-5Q) to CT-DNA were examined using UV-Vis, fluorescence spectra, thermal denaturation profiles and K SV values. Besides, thermodynamic studies indicated that binding of 3Q-5Q to DNA was spontaneous. On the other hand, in vitro phototoxicity and

Reactivity-based drug discovery using vitamin B(6)-derived pharmacophores.

PubMed

Wondrak, Georg T

2008-05-01

Endogenous reactive intermediates including photoexcited states of tissue chromophores, reactive oxygen species (ROS), reactive carbonyl species (RCS), transition metal ions, and Schiff bases have been implicated in the initiation and progression of diverse human pathologies including tumorigenesis, atherosclerosis, diabetes, and neurodegenerative disease. In contrast to structure-based approaches that target macromolecules by selective ligands, reactivity-based drug discovery uses chemical reagents as therapeutics that target reactive chemical species involved in human pathology. Reactivity-based design of prototype agents that effectively antagonize, modulate, and potentially even reverse the chemistry underlying tissue damage from oxidative and carbonyl stress therefore holds great promise in delivering significant therapeutic benefit. Apart from its established role as an essential cofactor for numerous enzymes, a large body of evidence suggests that B(6)-vitamers contain reactive pharmacophores that mediate therapeutically useful non-vitamin drug actions as potent antioxidants, metal chelators, carbonyl scavengers, Schiff base forming agents, and photosensitizers. Based on the fascinating chemical versatility of B(6)-derived pharmacophores, B(6)-vitamers are therefore promising lead compounds for reactivity-based drug design.

Elucidating the Nature of the Excited State of a Heteroleptic Copper Photosensitizer by using Time-Resolved X-ray Absorption Spectroscopy.

PubMed

Moonshiram, Dooshaye; Garrido-Barros, Pablo; Gimbert-Suriñach, Carolina; Picón, Antonio; Liu, Cunming; Zhang, Xiaoyi; Karnahl, Michael; Llobet, Antoni

2018-04-25

We report the light-induced electronic and geometric changes taking place within a heteroleptic Cu I photosensitizer, namely [(xant)Cu(Me 2 phenPh 2 )]PF 6 (xant=xantphos, Me 2 phenPh 2 =bathocuproine), by time-resolved X-ray absorption spectroscopy in the ps-μs time regime. Time-resolved X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis enabled the elucidation of the electronic and structural configuration of the copper center in the excited state as well as its decay dynamics in different solvent conditions with and without triethylamine acting as a sacrificial electron donor. A three-fold decrease in the decay lifetime of the excited state is observed in the presence of triethylamine, showing the feasibility of the reductive quenching pathway in the latter case. A prominent pre-edge feature is observed in the XANES spectrum of the excited state upon metal to charge ligand transfer transition, showing an increased hybridization of the 3d states with the ligand p orbitals in the tetrahedron around the Cu center. EXAFS and density functional theory illustrate a significant shortening of the Cu-N and an elongation of the Cu-P bonds together with a decrease in the torsional angle between the xantphos and bathocuproine ligand. This study provides mechanistic time-resolved understanding for the development of improved heteroleptic Cu I photosensitizers, which can be used for the light-driven production of hydrogen from water. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surface interaction between cubic phase NaNbO3 nanoflowers and Ru nanoparticles for enhancing visible-light driven photosensitized photocatalysis

NASA Astrophysics Data System (ADS)

Chen, Wei; Hu, Yin; Ba, Mingwei

2018-03-01

Ru nanoparticles supported on perovskite NaNbO3 with cubic crystal structure and nanoflower-like morphology was prepared by a convenient solvothermal method combined with photo-deposition technique. Crystal structure, chemical component and surface valence states determined by XRD, XPS, TEM and SEM demonstrated the metastable cubic phase of perovskite NaNbO3, and its modified surface by Ru species. Optical and electrochemical analysis, such as UV-vis DRS, OTCS and EIS, indicated the excellent photoelectrochemical properties and the efficient electron transfer of the composites. Compared with naked and Ru-doped NaNbO3, the composite photocatalyst exhibited outstanding performance for the degradation of RhB under visible light irradiation due to the dye self-photosensitization and the surface interaction between Ru metal nanoparticles and semiconductor. In-situ reduction of surface Ru oxide species in the photocatalytic process assisted the further improvement of the photocatalytic activity and stability. Investigation of the main active species during the photocatalysis confirmed the efficient transfer of the photo-generated electrons and the positive effect of oxygen defects in NaNbO3. Finally, possible mechanism of the present visible-light driven photocatalysis was proposed in detail. This work provided an alternative strategy to enhance the visible-light photocatalytic efficiency of the catalyst with wide band gap on the basis of the synergistic effect of dye self-photosensitization, interaction between NaNbO3 and its surface Ru nanoparticles, and the "self-doping" of oxygen defects in NaNbO3.

Higher-efficiency photoelectrochemical electrodes of titanium dioxide-based nanoarrays sensitized simultaneously with plasmonic silver nanoparticles and multiple metal sulfides photosensitizers

NASA Astrophysics Data System (ADS)

Guo, Keying; Liu, Zhifeng; Han, Jianhua; Zhang, Xueqi; Li, Yajun; Hong, Tiantian; Zhou, Cailou

2015-07-01

This paper describes a novel design of high-efficiency photoelectrochemical water splitting electrode, i.e., ordered TiO2 nanorod arrays (NRs) sensitized simultaneously with noble metal (Ag), binary metal sulfides (Ag2S) and ternary metal sulfides (Ag3CuS2) multiple photosensitizers for the first time. The TiO2/Ag/Ag2S/Ag3CuS2 NRs heterostructure is successfully synthesized through successive ion layer adsorption and reaction (SILAR) and a simple ion-exchange process based on ionic reaction mechanism. On the basis of an optimal quantity of Ag, Ag2S and Ag3CuS2 nanoparticles, such TiO2/Ag/Ag2S/Ag3CuS2 NRs exhibit a higher photoelectrochemical activity ever reported for TiO2-based nanoarrays in PEC water splitting, the photocurrent density is up to 9.82 mA cm-2 at 0.47 V versus Ag/AgCl, respectively. This novel architecture is able to increase electron collection efficiency and suppress carrier recombination via (i) a higher efficiency of light-harvesting through these multiple photosensitizers (Ag, Ag2S and Ag3CuS2); (ii) the efficient separation of photo-induced electrons and holes due to the direct electrical pathways; (iii) the surface plasmon resonance (SPR) effect of Ag nanoparticles, which enhances the efficient charge separation and high carrier mobility. This work is useful to explore feasible routes to further enhance the performance of oxide semiconductors for PEC water splitting to produce clean H2 energy.

[Effect of procaine and procaine metabolites on coenzyme A and acetyl coenzyme A concentration in various tissues of the rat].

PubMed

Kietzmann, M; Kaemmerer, K

1989-01-01

In rats treated with procaine hydrochloride, diethylaminoethanol, monoethylaminoethanol, ethanolamine, as well as a combination of procaine hydrochloride and haematoporphyrine the ratio of acetyl coenzyme A and coenzyme A clearly was enhanced in the liver and to a minor extent in the cerebellum. In the tissue of cerebral cortex, heart, muscle and duodenum no corresponding effects were demonstrated. These findings, showing a further intermediary effect of orally administered procaine, can be interpreted as an influence in intermediary energy utilisation.

Five years experience of photodynamic therapy with new chlorin photosensitizer

NASA Astrophysics Data System (ADS)

Privalov, Valery A.; Lappa, Alexander V.; Kochneva, Elena V.

2005-08-01

Clinical results of photodynamic therapy (PDT) with a novel natural second generation chlorin-type photosensitizer "Radachlorin", mainly consisting of sodium chlorine e6, are presented. This sensitizer possesses a number of advantages over sensitizers of hematoporphyrin and phthalocyanine types. In particular, Radachlorin is excreted from organism much faster (in 1-2 days), as a result the problem of patient light hypersensitivity for a few months is non-actual for Radachlorin. As light source there was used a 662 nm diode laser specially designed for PDT with Radachlorin. The 5 year clinical results of PDT application to 89 patients with different malignant tumors are summarized and analysed. It is shown in particular that PDT with Radachlorin is a radical high efficient method for treatment of basal cell carcinoma of skin. At intravenous introduction in drug dose 0.5 mg/kg with light fluence 300-350 J/cm2 or in dose 1 mg/kg with fluence 200-250 J/cm2 the method gives full recovery in almost 100% cases with excellent cosmetic effect. The method was successfully combined with surgical operations, laser ablations, radio- and chemotherapy. Preoperative and intraoperative PDT favors improvement of results in complex treatment of malignant tumors. The method has a potential as palliative measure; in a number of incurable cases it allowed us to achieve recanalization of obturated hollow organs, eliminate the inflammatory complications, and as a result to improve life quality.

Hydrogen Bond Acceptors and Additional Cationic Charges in Methylene Blue Derivatives: Photophysics and Antimicrobial Efficiency

PubMed Central

Felgenträger, Ariane; Maisch, Tim; Dobler, Daniel; Späth, Andreas

2013-01-01

Photodynamic inactivation of bacteria (PIB) by efficient singlet oxygen photosensitizers might be a beneficial alternative to antibiotics in the struggle against multiresistant bacteria. Phenothiazinium dyes belong to the most prominent classes of such sensitizers due to their intense absorption in the red-light region (λ abs, max ca. 600–680 nm, ε > 50000 L mol−1 cm−1), their low toxicity, and their attachment/penetration abilities. Except simple substituents like alkyl or hydroxyalkyl residues, nearly no modifications of the phenothiaziniums have been pursued at the auxochromic sites. By this, the properties of methylene blue derivatives and their fields of application are limited; it remains unclear if their potential antimicrobial efficacy may be enhanced, also to compete with porphyrins. We prepared a set of six mainly novel methylene blue derivatives with the ability of additional hydrogen bonding and/or additional cationic charges to study the substituents' effect on their activity/toxicity profiles and photophysical properties. Direct detection of singlet oxygen was performed at 1270 nm and the singlet oxygen quantum yields were determined. In suspensions with both, Gram-positive and Gram-negative bacteria, some derivatives were highly active upon illumination to inactivate S. aureus and E. coli up to 7 log10 steps (99.99999%) without inherent toxicities in the nonirradiated state. PMID:23509728

Direct Fabrication of the Graphene-Based Composite for Cancer Phototherapy through Graphite Exfoliation with a Photosensitizer.

PubMed

Liu, Gang; Qin, Hongmei; Amano, Tsukuru; Murakami, Takashi; Komatsu, Naoki

2015-10-28

We report on the application of pristine graphene as a drug carrier for phototherapy (PT). The loading of a photosensitizer, chlorin e6 (Ce6), was achieved simply by sonication of Ce6 and graphite in an aqueous solution. During the loading process, graphite was gradually exfoliated to graphene to give its composite with Ce6 (G-Ce6). This one-step approach is considered to be superior to the graphene oxide (GO)-based composites, which required pretreatment of graphite by strong oxidation. Additionally, the directly exfoliated graphene ensured a high drug loading capacity, 160 wt %, which is about 10 times larger than that of the functionalized GO. Furthermore, the Ce6 concentration for killing cells by G-Ce6 is 6-75 times less than that of the other Ce6 composites including GO-Ce6.

The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy.

PubMed

Silman, Israel; Roth, Esther; Paz, Aviv; Triquigneaux, Mathilde M; Ehrenshaft, Marilyn; Xu, Yechun; Shnyrov, Valery L; Sussman, Joel L; Deterding, Leesa J; Ashani, Yacov; Mason, Ronald P; Weiner, Lev

2013-03-25

The photosensitizer, methylene blue (MB), generates singlet oxygen ((1)O2) that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS), or bridging them. Data concerning both reversible and irreversible inhibition are here reviewed. MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a ~8 °C increase in the denaturation temperature. The crystal structure of the MB/TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS. The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo-oxidation, both being converted to NFK. In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented. Thus, photo-oxidative damage caused by MB involves targeted release of (1)O2 by the bound photosensitizer within the aqueous milieu of the active-site gorge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Photosensitizer adhered to cell culture microplates induces phototoxicity in carcinoma cells.

PubMed

Ziegler, Verena; Kiesslich, Tobias; Krammer, Barbara; Plaetzer, Kristjan

2013-01-01

In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings.

Photosensitizer Adhered to Cell Culture Microplates Induces Phototoxicity in Carcinoma Cells

PubMed Central

Ziegler, Verena; Kiesslich, Tobias; Krammer, Barbara; Plaetzer, Kristjan

2013-01-01

In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings. PMID:23509741

Acridine Orange as a Novel Photosensitizer for Photodynamic Therapy in Glioblastoma.

PubMed

Osman, Hany; Elsahy, Deena; Saadatzadeh, M Reza; Pollok, Karen E; Yocom, Steven; Hattab, Eyas M; Georges, Joseph; Cohen-Gadol, Aaron A

2018-06-01

Photodynamic therapy combines the effects of a chemical agent with the physical energy from light or radiation to result in lysis of cells. Acridine orange (AO) is a molecule with fluorescence properties that has been demonstrated to possess photosensitizing properties. The objective of this study was to investigate the photodynamic effect of AO on glioblastoma cell viability and growth. Glioblastoma cells (N = 8000 cells/well at 0 hours) were exposed to AO followed by white unfiltered light-emitting diode light. Cultures were exposed to either 10 or 30 minutes of light. The cell number per well was determined at 0, 24, 48, and 72 hours after exposure. A dramatic cytocidal effect of AO after exposure to 10 minutes of white light was observed. There was almost complete eradication of glioblastoma cells over a 72-hour period. Although AO or light alone exhibited some effect on cell growth, it was not as pronounced as the combination of AO and light. This is the first study to our knowledge to demonstrate the photodynamic effect of AO in glioblastoma cells. These data support the need for further studies to characterize and evaluate whether this striking cytotoxic effect can be achieved in vivo. The combination of AO and exposure to white unfiltered light-emitting diode light may have potential future applications in management of glioblastoma. Copyright © 2018 Elsevier Inc. All rights reserved.

Singlet oxygen generation of photosensitizers effectively activated by Nd3+-doped upconversion nanoparticles of luminescence intensity enhancing with shell thickness decreasing

NASA Astrophysics Data System (ADS)

Zou, Haixia; Jin, Fengmin; Song, Xiaoyan; Xing, Jinfeng

2017-04-01

The introduction of a thick shell structure has been widely used to enhance the emission intensity of upconversion nanoparticles (UCNPs). However, a thick shell could increase the distance between UCNPs and photosensitizers, which is not favourable to the generation of singlet oxygen (1O2) in photodynamic therapy (PDT) due to the low fluorescence resonance energy transfer (FRET) efficiency. In this study, we used a facile method to prepare UCNPs that the emission intensity could increase with the shell thickness decreasing, which facilitated the efficient FRET between UCNPs and photosensitizers. In detail, the Nd3+-doped UCNPs with different dopant concentration of Yb3+ were prepared and characterized firstly. The Ir/g (intensity of red luminescence to green luminescence) was tuned to increase largely by precisely controlling Yb3+ concentration in core-shell, which could make UCNPs effectively activate methylene blue (MB). Then, a unique procedure was used to prepare NaYF4:Yb/Er/Nd@NaYF4:Nd (Yb3+:30%) core-shell nanoparticles with different shell thickness by tuning the amount of the core. The upconversion luminescence (UCL) intensity of those UCNPs enhanced dramatically with the shell thickness decreasing. Furthermore, UCNPs and MB were encapsulated into SiO2 nanoparticles. FRET efficiency between UCNPs and MB largely increased with the shell thickness of UCNPs decreasing. Correspondingly, the efficiency of 1O2 generation obviously increased. We provided a new method to optimize the UCL intensity and FRET efficiency at the same time to produce 1O2 efficiently.

Photosensitization of InP/ZnS quantum dots for anti-cancer and anti-microbial applications

NASA Astrophysics Data System (ADS)

Nadeau, Jay; Chibli, Hicham; Carlini, Lina

2012-03-01

Cadmium-free quantum dots (QDs), such as those made from InP, show similar optical properties to those containing toxic heavy metals and thus provide a promising alternative for imaging and therapeutics. The band gap of InP is similar to that of CdTe, so photosensitization of InP QDs with porphyrins or other dyes should lead to generation of reactive oxygen species, useful for targeted destruction of malignant cells or pathogenic bacteria. Here we show the results of measurements of singlet oxygen and superoxide generation from InP QDs with single and double ZnS shells compared with CdTe and CdSe/ZnS. Reactive oxygen species are measured using colorimetric or fluorescent reporter assays and spin-trap electron paramagnetic resonance (EPR) spectroscopy. We find that the size of the InP QDs and the thickness of the ZnS shell both strongly influence ROS generation. These results suggest future approaches to the design of therapeutic nanoparticles.

Broad-spectrum photoprotection: the roles of tinted auto windows, sunscreens and browning agents in the diagnosis and treatment of photosensitivity.

PubMed

Johnson, J A; Fusaro, R M

1992-01-01

Since window glass absorbs sunlight below 320 nm, it provides a means of assessing sensitivity to longer wavelengths, i.e. UVA and visible radiation. Positive responses to the query of whether symptoms develop in the auto with the windows up must now be interpreted with regard to the possible presence of tinted plastic film on side and rear windows. These films block nearly all UVA radiation, as does the plastic interleaf of windshields. Thus, occupants of an auto equipped with plastic film receive photoprotection from UVB radiation and well into the UVA region. We define three classes of topical sunscreens: (1) conventional UVB screens, (2) broad-spectrum preparations containing a UVB screen and a UVA absorber and (3) browning agents such as dihydroxyacetone (DHA) that produce a skin coloration that absorbs in the low end of the visible region, with overlap into long-wavelength UVA. By considering responses of photosensitive persons in autos with tinted or untinted windows, coupled with efficacy of appropriate sunscreens, we produced an algorithm defining three photosensitivity subsets. Persons sensitive to long-wavelength UVA and/or visible radiation will benefit from tinted auto windows. In particular, patients with lupus erythematosus (LE) have actively promoted legislation allowing tinted windows. Support for their position is documented by recent reports of induction of lesions in LE patients by exposure to UVA and visible radiation. The brown color produced by DHA is a useful adjunct to the screening action of broad-spectrum sunscreens. Development of a durable color overnight allows application of the DHA preparation in the evening, thus eliminating possible interference with sunscreen use during the day.

Hydrothermally Processed Photosensitive Field-Effect Transistor Based on ZnO Nanorod Networks

NASA Astrophysics Data System (ADS)

Kumar, Ashish; Bhargava, Kshitij; Dixit, Tejendra; Palani, I. A.; Singh, Vipul

2016-11-01

Formation of a stable, reproducible zinc oxide (ZnO) nanorod-network-based photosensitive field-effect transistor using a hydrothermal process at low temperature has been demonstrated. K2Cr2O7 additive was used to improve adhesion and facilitate growth of the ZnO nanorod network over the SiO2/Si substrate. Transistor characteristics obtained in the dark resemble those of the n-channel-mode field-effect transistor (FET). The devices showed I on/ I off ratio above 8 × 102 under dark condition, field-effect mobility of 4.49 cm2 V-1 s-1, and threshold voltage of -12 V. Further, under ultraviolet (UV) illumination, the FET exhibited sensitivity of 2.7 × 102 in off-state (-10 V) versus 1.4 in on-state (+9.7 V) of operation. FETs based on such nanorod networks showed good photoresponse, which is attributed to the large surface area of the nanorod network. The growth temperature for ZnO nanorod networks was kept at 110°C, enabling a low-temperature, cost-effective, simple approach for high-performance ZnO-based FETs for large-scale production. The role of network interfaces in the FET performance is also discussed.

Design of high power LED-based UVA emission system and a photosensitive substance for clinical application in corneal radiation

NASA Astrophysics Data System (ADS)

Mota, Alessandro D.; Cestari, André M.; de Oliveira, André O.; Oliveira, Anselmo G.; Terruggi, Cristina H. B.; Rossi, Giuliano; Castro, Jarbas C.; Ligabô, João. P. B.; Ortega, Tiago A.; Rosa, Tiago

2015-09-01

This work presents an innovative cross-linking procedure to keratoconus treatment, a corneal disease. It includes the development of an ultraviolet controlled emission portable device based on LED source and a new formulation of a photosensitive drug called riboflavin. Thus new formulation improves drug administration by its transepithelial property. The UV reaction with riboflavin in corneal tissue leads to a modification of corneal collagen fibers, turning them more rigid and dense, and consequently restraining the advance of the disease. We present the control procedures to maintain UV output power stable up to 45mw/cm2, the optical architecture that leads to a homogeneous UV spot and the new formulation of Riboflavin.

Studies on cytostatics used as photosensitizing material in photodynamic therapy

NASA Astrophysics Data System (ADS)

Pascu, Mihail-Lucian; Danaila, Leon; Carstocea, Benone D.; Staicu, Angela; Truica, Sorina; Gazdaru, Doina M.

2002-10-01

Introduction of the photosensitizer properties of cytostatics drus was made, pointing out that the fact that besides the biochemical action of the cytostatics their effects could be enhanced by the exposure to light at different doses. A spectroscopical characterisation of methotrexate and fluorouracil, cytostatic drugs used frequently in cancer therpy was performed. The absorption, emission and excitation spectra were measured for methotrexate solutions in natural saline and sodium hydroxide at concentration in the range 10-5 -10-6M and pH 8.4. The absorption, emission and excitation spectra were measured for fluorouracil solutions in natural saline at concentration in the range 10-4 -10-5M. The absorption spectrum exhibits spectral bands in the range 250nm -450nm for both drugs. The fluorescence excitatioan for methotrexate was made at 340nm and 370nm, the fluorescence emission was detected in the spectral range 400nm - 500nm with a maximum at 470nm. The fluorescence excitation was measured in teh range 200nm-500nm with the emission centred on 530nm, for Xe lamp irradiation, and 300nm for Hg lamp and laser irradiation. The fluorescence emission spectra was monitored in the spectral range 400nm - 600nm. The effects of irradiation on spectroscopic characteristics of methrotrexate and fluorouracil were investigated. The irraditaion was made using a UV classic lamp with Xe, for the first experimental part and for the second one it was used both a class Hg lamp and a nytorgen pulsed laser.

Photosensitization of CdSe/ZnS QDs and reliability of assays for reactive oxygen species production.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, D. R.; Dimitrijevic, N. M.; Nadeau, J. L.

CdSe/ZnS quantum dots (QDs) conjugated to biomolecules that can act as electron donors are said to be 'photosensitized': that is, they are able to oxidize or reduce molecules whose redox potential lies inside their band edges, in particular molecular oxygen and water. This leads to the formation of reactive oxygen species (ROS) and phototoxicity. In this work, we quantify the generation of different forms of ROS from as-synthesized QDs in toluene; water-solubilized, unconjugated QDs; QDs conjugated to the neurotransmitter dopamine; and dopamine alone. Results of indirect fluorescent ROS assays, both in solution and inside cells, are compared with those ofmore » spin-trap electron paramagentic resonance spectroscopy (EPR). The effect of these particles on the metabolism of mammalian cells is shown to be dependent upon light exposure and proportional to the amount of ROS generated.« less

Visualization of Porphyrin-Based Photosensitizer Distribution from Fluorescence Images In Vivo Using an Optimized RGB Camera

NASA Astrophysics Data System (ADS)

Liu, L.; Huang, Zh.; Qiu, Zh.; Li, B.

2018-01-01

A handheld RGB camera was developed to monitor the in vivo distribution of porphyrin-based photosensitizer (PS) hematoporphyrin monomethyl ether (HMME) in blood vessels during photodynamic therapy (PDT). The focal length, f-number, International Standardization Organization (ISO) sensitivity, and shutter speed of the camera were optimized for the solution sample with various HMME concentrations. After the parameter optimization, it was found that the red intensity value of the fluorescence image was linearly related to the fluorescence intensity under investigated conditions. The RGB camera was then used to monitor the in vivo distribution of HMME in blood vessels in a skin-fold window chamber model. The red intensity value of the recorded RGB fluorescence image was found to be linearly correlated to HMME concentrations in the range 0-24 μM. Significant differences in the red to green intensity ratios were observed between the blood vessels and the surrounding tissue.

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PubMed

Ciulla, Thomas A; Criswell, Mark H; Danis, Ronald P; Snyder, Wendy J; Small, Ward

2004-08-01

To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

A safety study of a novel photosensitizer, sinoporphyrin sodium, for photodynamic therapy in Beagle dogs.

PubMed

Lin, Ni; Li, Chao; Wang, Zhonghua; Zhang, Jingxuan; Ye, Xiangfeng; Gao, Wenjing; Wang, Aiping; Jin, Hongtao; Wei, Jinfeng

2015-04-01

Sinoporphyrin sodium (DVDMS) is a novel hematoporphyrin-like photosensitizer developed for photodynamic therapy (PDT), an effective therapeutic modality for tumor treatment; however, the safety of photosensitizer-based PDT is always of great concern. The purpose of the current study was to investigate the potential repeated-dose toxicity and describe the toxicokinetic process of DVDMS-based PDT in Beagle dogs. The dogs were randomly allocated to six groups, and then were administrated a DVDMS preparation intravenously at dose levels of 0, 1, 3, 9, 1 and 9 mg per kg body weight, respectively; then, the latter two groups were illuminated 24 h later with a 630 nm laser for 10 min, once every seven days for 5 weeks. During the study period, clinical signs, mortality, body weight, food consumption, body temperature, ophthalmoscopy, hematology, serum biochemistry, urinalysis, electrocardiograms, toxicokinetics, organ weights, gross anatomy and histopathology were examined. After the administration, no deaths were observed; however, the dogs that received PDT showed skin swelling and ulceration, indicating that DVDMS-PDT induced a phototoxic effect. DVDMS led to an increase in blood coagulation in dogs in the 9 mg kg(-1) group and in the two PDT groups on Day 35, whereas it induced a decrease in dogs in the 3 mg kg(-1) group and in the two PDT groups on Day 49. The toxicokinetic study showed that the systematic exposure of DVDMS in dogs occurred in a dose-dependent manner, and DVDMS did not accumulate in blood plasma. The DVDMS-based PDT group showed no obvious treatment-related pathological changes; however, slight or mild brown-and-yellow pigmentation of DVDMS (or its metabolite) was observed to deposit in the liver, spleen, local lymph nodes and marrow of dogs in the mid- and high-dose groups, as well as the high-dose PDT group. In females, the absolute and relative spleen weights increased in dogs in the 9 mg kg(-1) DVDMS groups with and without PDT during the

Photogeneration of singlet oxygen by the phenothiazine derivatives covalently bound to the surface-modified glassy carbon

NASA Astrophysics Data System (ADS)

Blacha-Grzechnik, Agata; Piwowar, Katarzyna; Krukiewicz, Katarzyna; Koscielniak, Piotr; Szuber, Jacek; Zak, Jerzy K.

2016-05-01

The selected group of four amine-derivatives of phenothiazine was covalently grafted to the glassy carbon surface in the four-step procedure consisting of the electrochemical reduction of the diazonium salt followed by the electrochemical and chemical post-modification steps. The proposed strategy involves the bonding of linker molecule to which the photosensitizer is attached. The synthesized organic layers were characterized by means of cyclic voltammetry, XPS and Raman Spectroscopy. It was shown that the phenothiazines immobilized via proposed strategy retain their photochemical properties and are able to generate 1O2 when activated by the laser radiation. The effectiveness of in situ singlet oxygen generation by those new solid photoactive materials was determined by means of UVVis spectroscopy. The reported, covalently modified solid surfaces may find their application as the singlet oxygen photogenerators in the fine chemicals' synthesis or in the wastewater treatment.

Final report of the Cosmetic Ingredient Review Expert Panel amended safety assessment of Calendula officinalis-derived cosmetic ingredients.

PubMed

Andersen, F Alan; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W

2010-01-01

Calendula officinalis extract, C officinalis flower, C officinalis flower extract, C officinalis flower oil, and C officinalis seed oil are cosmetic ingredients derived from C officinalis. These ingredients may contain minerals, carbohydrates, lipids, phenolic acids, flavonoids, tannins, coumarins, sterols and steroids, monoterpenes, sesquiterpenes, triterpenes, tocopherols, quinones, amino acids, and resins. These ingredients were not significantly toxic in single-dose oral studies using animals. The absence of reproductive/developmental toxicity was inferred from repeat-dose studies of coriander oil, with a similar composition. Overall, these ingredients were not genotoxic. They also were not irritating, sensitizing, or photosensitizing in animal or clinical tests but may be mild ocular irritants. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that these ingredients are safe for use in cosmetics in the practices of use and concentration given in this amended safety assessment.

Reactive oxygen species in plant pathogenesis: the role of perylenequinone photosensitizers.

PubMed

Daub, Margaret E; Herrero, Sonia; Chung, Kuang-Ren

2013-09-20

Reactive oxygen species (ROS) play multiple roles in interactions between plants and microbes, both as host defense mechanisms and as mediators of pathogenic and symbiotic associations. One source of ROS in these interactions are photoactivated, ROS-generating perylenequinone pigments produced via polyketide metabolic pathways in plant-associated fungi. These natural products, including cercosporin, elsinochromes, hypocrellins, and calphostin C, are being utilized as medicinal agents, enzyme inhibitors, and in tumor therapy, but in nature, they play a role in the establishment of pathogenic associations between fungi and their plant hosts. Photoactivated perylenequinones are photosensitizers that use light energy to form singlet oxygen (¹O₂) and free radical oxygen species which damage cellular components based on localization of the perylenequinone molecule. Production of perylenequinones during infection commonly results in lipid peroxidation and membrane damage, leading to leakage of nutrients from cells into the intercellular spaces colonized by the pathogen. Perylenequinones show almost universal toxicity against organisms, including plants, mice, bacteria, and most fungi. The producing fungi are resistant, however, and serve as models for understanding resistance mechanisms. Studies of resistance mechanisms by perylenequinone-producing fungi such as Cercospora species are leading to an understanding of cellular resistance to ¹O₂ and oxidative stress. Recent studies show commonalities between resistance mechanisms in these fungi with extensive studies of ¹O₂ and oxidative stress responses in photosynthetic organisms. Such studies hold promise both for improved medical use and for engineering crop plants for disease resistance.

Refuse derived soluble bio-organics enhancing tomato plant growth and productivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sortino, Orazio; Dipasquale, Mauro; Montoneri, Enzo, E-mail: enzo.montoneri@unito.it

2012-10-15

Highlights: Black-Right-Pointing-Pointer Municipal bio-wastes are a sustainable source of bio-based products. Black-Right-Pointing-Pointer Refuse derived soluble bio-organics promote chlorophyll synthesis. Black-Right-Pointing-Pointer Refuse derived soluble bio-organics enhance plant growth and fruit ripening rate. Black-Right-Pointing-Pointer Sustainable chemistry exploiting urban refuse allows sustainable development. Black-Right-Pointing-Pointer Chemistry, agriculture and the environment benefit from biowaste technology. - Abstract: Municipal bio-refuse (CVD), containing kitchen wastes, home gardening residues and public park trimmings, was treated with alkali to yield a soluble bio-organic fraction (SBO) and an insoluble residue. These materials were characterized using elemental analysis, potentiometric titration, and 13C NMR spectroscopy, and then applied as organic fertilizers tomore » soil for tomato greenhouse cultivation. Their performance was compared with a commercial product obtained from animal residues. Plant growth, fruit yield and quality, and soil and leaf chemical composition were the selected performance indicators. The SBO exhibited the best performance by enhancing leaf chlorophyll content, improving plant growth and fruit ripening rate and yield. No product performance-chemical composition relationship could be assessed. Solubility could be one reason for the superior performance of SBO as a tomato growth promoter. The enhancement of leaf chlorophyll content is discussed to identify a possible link with the SBO photosensitizing properties that have been demonstrated in other work, and thus with photosynthetic performance.« less

Environmental influences on the photooxidation of manganese by a zinc porphyrin sensitizer

PubMed Central

Wohlgemuth, Roland; Otvos, John W.; Calvin, Melvin

1982-01-01

The photosensitized oxidation of a membrane-bound Mn(III) tetrapyridylporphyrin derivative by a Zn tetrapyridylporphyrin derivative, which is confined to the membrane, has been achieved in negatively charged membranes consisting of phosphatidylglycerol or phosphatidic acid. At the same time, the zwitterionic electron acceptor, propylviologen sulfonate (PVS0), is reduced in the aqueous phase. The same reaction cannot be obtained with zwitterionic or cationic membranes, nor does this photosensitized reaction take place in a homogeneous solution with Mn(III) tetrapyridylporphyrin and Zn tetrapyridylporphyrin. These results show that the organization of donor, sensitizer, and acceptor at an appropriately selected interface allows reactions that would not occur in homogeneous solutions. PMID:16593221

Environmental Influences on the Photooxidation of Manganese by a Zinc Porphyrin Sensitizer

NASA Astrophysics Data System (ADS)

Wohlgemuth, Roland; Otvos, John W.; Calvin, Melvin

1982-08-01

The photosensitized oxidation of a membrane-bound Mn(III) tetrapyridylporphyrin derivative by a Zn tetrapyridylporphyrin derivative, which is confined to the membrane, has been achieved in negatively charged membranes consisting of phosphatidylglycerol or phosphatidic acid. At the same time, the zwitterionic electron acceptor, propylviologen sulfonate (PVS0), is reduced in the aqueous phase. The same reaction cannot be obtained with zwitterionic or cationic membranes, nor does this photosensitized reaction take place in a homogeneous solution with Mn(III) tetrapyridylporphyrin and Zn tetrapyridylporphyrin. These results show that the organization of donor, sensitizer, and acceptor at an appropriately selected interface allows reactions that would not occur in homogeneous solutions.

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

PubMed Central

Kralova, Jarmila; Kolar, Michal; Kahle, Michal; Truksa, Jaroslav; Lettlova, Sandra; Balusikova, Kamila; Bartunek, Petr

2017-01-01

The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design. PMID:28295025

Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin, Electroporation enhances antimicrobial photodynamic inactivation

PubMed Central

de Melo, Wanessa de Cássia Martins Antunes; Lee, Alexander N; Perussi, Janice Rodrigues; Hamblin, Michael R.

2013-01-01

The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this study we evaluated the combination of aPDT mediated by the hydrophobic PS, hypericin and EP (aPDT/EP) against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. These bacteria were exposed to light (590 nm) in the presence of hypericin (4µM), following electroporation. The results showed that aPDT/EP inactivated 3.67 logs more E. coli and 2.65 logs more S. aureus than aPDT alone. Based on these results we suggest that EP can potentiate the aPDT effect. PMID:24284122

Semiconductive Copper(I)-Organic Frameworks for Efficient Light-Driven Hydrogen Generation Without Additional Photosensitizers and Cocatalysts.

PubMed

Shi, Dongying; Zheng, Rui; Sun, Ming-Jun; Cao, Xinrui; Sun, Chun-Xiao; Cui, Chao-Jie; Liu, Chun-Sen; Zhao, Junwei; Du, Miao

2017-11-13

As the first example of a photocatalytic system for splitting water without additional cocatalysts and photosensitizers, the comparatively cost-effective Cu 2 I 2 -based MOF, Cu-I-bpy (bpy=4,4'-bipyridine) exhibited highly efficient photocatalytic hydrogen production (7.09 mmol g -1  h -1 ). Density functional theory (DFT) calculations established the electronic structures of Cu-I-bpy with a narrow band gap of 2.05 eV, indicating its semiconductive behavior, which is consistent with the experimental value of 2.00 eV. The proposed mechanism demonstrates that Cu 2 I 2 clusters of Cu-I-bpy serve as photoelectron generators to accelerate the copper(I) hydride interaction, providing redox reaction sites for hydrogen evolution. The highly stable cocatalyst-free and self-sensitized Cu-I-bpy provides new insights into the future design of cost-effective d 10 -based MOFs for highly efficient and long-term solar fuels production. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Action of the photosensitizer QLT0074 upon human T lymphocytes in vitro

NASA Astrophysics Data System (ADS)

Hunt, David W. C.; Jiang, Huijun; Salmon, Ruth A.; Granville, David J.; North, John R.; Richter, Anna M.

2001-04-01

A new photosensitizer, presently designated QLT0074, may be useful for the treatment of skin conditions, particularly those mediated by T lymphocytes, with photodynamic therapy (PDT). QLT0074 was tested against human peripheral blood T cells and Jurkat T lymphoma cells. Low concentrations of QLT0074 and blue light were sufficient to induce apoptosis in peripheral blood T cells or Jurkat T lymphoma cells as indicated by expression of the apoptosis-associated mitochondrial 7A6 marker, annexin-V labeling or activation of capsase-3 and cleavage of the capsase substrate poly(ADP-ribose)polymerase (PARP). Flow cytometry studies performed following PDT showed that peripheral blood T cells with high expression of the interleukin-2 receptor (CD25) took up greater amounts of QLT0074 and were eliminated to a greater degree than T cells with low CD25 levels. This effect of PDT was also shown by the reduction in the percentage of T cells that expressed other activation-associated markers such as very late activation antigen-4 (CD49d), human leukocyte antigen DR (HLA-DR), intercellular adhesion molecule-1 (CD54) and Fas (CD95). In the case of T cells that remained viable following PDT, CD25 expression was lower while CD54, CD95 and HLA-DR levels were unchanged. Thus, PDT with QLT0074 has selective, dose-dependent effects on T cells in vitro.

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

PubMed

Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

2015-01-01

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

Bovine serum albumin nanoparticles loaded with Photosens photosensitizer for effective photodynamic therapy

NASA Astrophysics Data System (ADS)

Khanadeev, Vitaly; Khlebtsov, Boris; Packirisamy, Gopinath; Khlebtsov, Nikolai

2017-03-01

Polymeric nanoparticles (NPs) are widely used for drug delivery applications due to high biodegradability, low toxicity and high loading capacity. The focus of this study is the development of photosensitizer Photosens (PS) loaded albumin NPs for efficient photodynamic therapy (PDT). To fabricate PS-loaded bovine serum albumin nanoparticles (BSA-PS NPs), we used a coacervation method with glutaraldehyde followed by passive loading of PS. Successful loading of PS was confirmed by appearance of characteristic peak in absorption spectrum which allows to determine the PS loading in BSA NPs. The synthesized BSA-PS NPs demonstrated low toxicity to HeLa cells at therapeutic concentrations of loaded PS. Compared to free PS solution, the synthesized BSA-PS NPs generated the singlet oxygen more effectively under laser irradiation at 660 nm. In addition, due to presence of various chemical groups on the surface of BSA-PS NPs, they are capable to adsorb on cell surface and accumulate in cells due to cellular uptake mechanisms. Owing to combination of PD and cell uptake advantages, BSA-PS NPs demonstrated higher efficacy of photodynamic damage to cancer cells as compared to free PS at equivalent concentrations. These results suggest that non-targeted BSA-PS NPs with high PD activity and low-fabrication costs of are promising candidates for transfer to PD clinic treatments.

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

PubMed Central

Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

2015-01-01

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS. PMID:26604753

Evaluation of electrical propagation delay with cardiomyocytes by photosensitization reaction in vitro

NASA Astrophysics Data System (ADS)

Doi, Marika; Ogawa, Emiyu; Arai, Tsunenori

2017-02-01

In order to study cardiomyocyte electrical conduction damage by a photosensitization reaction (PR) mostly comes from outside of the cells in a few minutes after the PR, we studied propagation delay of contact action potential with cardiomyocyte by the PR. To determine appropriate PR condition for tachyarrhythmia ablation, a precise electrophysiological experiment in vitro has been preferable. We measured the contact action potential using a microelectrode array system of which information may be correct than conventional Ca2+ measurement. We investigated the propagation delays of an evoked potential to evaluate the electrical conduction damage by the PR. Rat cardiomyocytes were cultivated for 5-7 days on a dish with which 64 electrodes were patterned, in an incubator controlled to 37°C, 5% CO2. The following conditions were used for the PR: 40 μg/ml talapordfin sodium and 290 mW/cm2, 40-78 J/cm2 for an irradiation. A 2D map was obtained to visualize the propagation delays of the evoked potential. The propagation speed, which was calculated based on the measured propagation delays, was decreased by about 30-50% on average of all electrodes after the PR. Therefore, we think 2D propagation delays measurement of the evoked potential with contact action potential measuring system might be available to evaluate the acute electrical conduction damage of cardiomyocyte by the PR.

Optimizing photodynamic therapy by liposomal formulation of the photosensitizer pyropheophorbide-a methyl ester: in vitro and ex vivo comparative biophysical investigations in a colon carcinoma cell line.

PubMed

Guelluy, Pierre-Henri; Fontaine-Aupart, Marie-Pierre; Grammenos, Angeliki; Lécart, Sandrine; Piette, Jacques; Hoebeke, Maryse

2010-09-24

Photodynamic therapy (PDT), induced by a photosensitizer (PS) encapsulated in a nanostructure, has emerged as an appropriate treatment to cure a multitude of oncological and non-oncological diseases. Pyropheophorbide-a methyl ester (PPME) is a second-generation PS tested in PDT, and is a potential candidate for future clinical applications. The present study, carried out in a human colon carcinoma cell line (HCT-116), evaluates the improvement resulting from a liposomal formulation of PPME versus free-PPME. Absorption and fluorescence spectroscopies, fluorescence lifetime measurements, subcellular imaging and co-localization analysis have been performed in order to analyze the properties of PPME for each delivery mode. The benefit of drug encapsulation in DMPC-liposomes is clear from our experiments, with a 5-fold higher intracellular drug delivery than that observed with free-PPME at similar concentrations. The reactive oxygen species (ROSs) produced after PPME-mediated photosensitization have been identified and quantified by using electron spin resonance spectroscopy. Our results demonstrate that PPME-PDT-mediated ROSs are composed of singlet oxygen and a hydroxyl radical. The small amounts of PPME inside mitochondria, as revealed by fluorescence co-localization analysis, could maybe explain the very low apoptotic cell death measured in HCT-116 cells.

Laser and Non-Coherent Light Effect on Peripheral Blood Normal and Acute Lymphoblastic Leukemic Cells by Using Different Types of Photosensitizers

NASA Astrophysics Data System (ADS)

El Batanouny, Mohamed H.; Khorshid, Amira M.; Arsanyos, Sonya F.; Shaheen, Hesham M.; Abdel Wahab, Nahed; Amin, Sherif N.; El Rouby, Mahmoud N.; Morsy, Mona I.

2010-04-01

Photodynamic therapy (PDT) is a novel treatment modality of cancer and non-cancerous conditions that are generally characterized by an overgrowth of unwanted or abnormal cells. Irradiation of photosensitizer loaded cells or tissues leads via the photochemical reactions of excited photosensitizer molecules to the production of singlet oxygen and free radicals, which initiate cell death. Many types of compounds have been tested as photosensitizers, such as methylene blue (MB) and photopherin seemed to be very promising. This study involved 26 cases of acute lymphoblastic leukemia and 15 normal volunteers as a control group. The cell viability was measured by Light microscope and flowcytometer. Mode of cell death was detected by flowcytometer and electron microscope in selected cases. The viability percentage of normal peripheral blood mononuclear cells (PBMC) incubated with methylene blue (MB) alone or combined with photo irradiation with diode laser (as measured by light microscope) was significantly lower than that of untreated cases either measured after 1 hour (p<0.001) or 24 hours (p<0.001) post incubation. There was a significantly lower viability percentage of normal cells incubated with MB and photoirradiated with diode laser compared to normal cells treated with MB alone for either measured after 1 hour (p<0.001) or 24 hours (p<0.001) post incubation. The decrease in viability was more enhanced with increasing the incubation time. For normal cells incubated with photopherin either for 1/2 an hour or 1 hour, there was a weak cytotoxic effect compared to the effect on untreated cells. There was a significant decrease in viability percentage of cells incubated with photopherin either for 1/2 an hour or 1 hour and photoirradiated with He:Ne laser compared to normal untreated cells. The decrease in the cell viability percentage was significantly lower with the use of PDT (photopherin and He:Ne laser ) compared to either photopherin alone or He:Ne laser alone. The

Stable azodye photo-alignment layer for liquid crystal devices achieved by "turning off" dye photosensitivity

NASA Astrophysics Data System (ADS)

McGinty, C.; Finnemeyer, V.; Reich, R.; Clark, H.; Berry, S.; Bos, P.

2017-11-01

We have previously proposed a low cost, versatile process for stabilizing azodye photo-alignment layers for liquid crystal devices by utilizing a surface localized reactive mesogen (RM) layer. The RM is applied by dissolving the monomer in a liquid crystal material prior to filling the cell. In this paper, we show the significant effect of azodye layer thickness on the long term stability of these alignment layers when exposed to polarized light. We demonstrate, surprisingly, that thin azodye layers (˜3 nm) provide improved stability over thicker (˜40 nm) layers. Using this process, we show cells which have been stable to exposure with polarized light through one month. Additionally, we demonstrate the use of a photo-alignment layer to align the liquid crystals that afterwards can be rendered insensitive to polarized light. This was accomplished by using the process described above with the additional step of eliminating the photosensitivity of the azodye layer through photo-bleaching; the result is an RM alignment layer that will be stable when exposed to polarized light in the dye absorption band.