Geographic variation in mimetic precision among different species of coral snake mimics.

PubMed

Akcali, C K; Pfennig, D W

2017-07-01

Batesian mimicry is widespread, but whether and why different species of mimics vary geographically in resemblance to their model is unclear. We characterized geographic variation in mimetic precision among four Batesian mimics of coral snakes. Each mimic occurs where its model is abundant (i.e. in 'deep sympatry'), rare (i.e. at the sympatry/allopatry boundary or 'edge sympatry') and absent (i.e. in allopatry). Geographic variation in mimetic precision was qualitatively different among these mimics. In one mimic, the most precise individuals occurred in edge sympatry; in another, they occurred in deep sympatry; in the third, they occurred in allopatry; and in the fourth, precise mimics were not concentrated anywhere throughout their range. Mimicry was less precise in allopatry than in sympatry in only two mimics. We present several nonmutually exclusive hypotheses for these patterns. Generally, examining geographic variation in mimetic precision - within and among different mimics - offers novel insights into the causes and consequences of mimicry. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

PubMed

Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

2015-03-18

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages

PubMed Central

Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J M

2015-01-01

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA–HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA–HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers. PMID:25650634

Silicon nanoparticles: applications in cell biology and medicine

PubMed Central

O’Farrell, Norah; Houlton, Andrew; Horrocks, Benjamin R

2006-01-01

In this review, we describe the synthesis, physical properties, surface functionalization, and biological applications of silicon nanoparticles (also known as quantum dots). We compare them against current technologies, such as fluorescent organic dyes and heavy metal chalcogenide-based quantum dots. In particular, we examine the many different methods that can be used to both create and modify these nanoparticles and the advantages they may have over current technologies that have stimulated research into designing silicon nanoparticles for in vitro and in vivo applications. PMID:17722279

Farnesyltransferase inhibitors: CAAX mimetics based on different biaryl scaffolds.

PubMed

Straniero, Valentina; Pallavicini, Marco; Chiodini, Giuseppe; Ruggeri, Paola; Fumagalli, Laura; Bolchi, Cristiano; Corsini, Alberto; Ferri, Nicola; Ricci, Chiara; Valoti, Ermanno

2014-07-01

Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed as farnesyltransferase (FTase) inhibitors (FTIs) by replacing AA with o-aryl or o-heteroaryl substituted p-hydroxy- or p-aminobenzoic acid, while maintaining the replacement of C with 1,4-benzodioxan-2-ylmethyl or 2-amino-4-thiazolylacetyl residue as in previous CAAX mimetics. Both FTase inhibition and antiproliferative effect were showed by two thiazole derivatives, namely those with 1-naphthyl (10 and 10a) or 3-furanyl (15 and 15a) in the central spacer, and by the benzodioxane derivative with 2-thienyl (6 and 6a) in the same position. Accumulation of unprenylated RAS was demonstrated in cells incubated with 15a. Consistently with FTIs literature, such results delineate the biaryl scaffold not only as a spacer but also as a sensible area of these mimetic molecules, where modifications at the branching aromatic ring are not indifferent and should be matter of further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tetra(p-tolyl)borate-functionalized solvent polymeric membrane: a facile and sensitive sensing platform for peroxidase and peroxidase mimetics.

PubMed

Wang, Xuewei; Qin, Wei

2013-07-22

The determination of peroxidase activities is the basis for enzyme-labeled bioaffinity assays, peroxidase-mimicking DNAzymes- and nanoparticles-based assays, and characterization of the catalytic functions of peroxidase mimetics. Here, a facile, sensitive, and cost-effective solvent polymeric membrane-based peroxidase detection platform is described that utilizes reaction intermediates with different pKa values from those of substrates and final products. Several key but long-debated intermediates in the peroxidative oxidation of o-phenylenediamine (o-PD) have been identified and their charge states have been estimated. By using a solvent polymeric membrane functionalized by an appropriate substituted tetraphenylborate as a receptor, those cationic intermediates could be transferred into the membrane from the aqueous phase to induce a large cationic potential response. Thus, the potentiometric indication of the o-PD oxidation catalyzed by peroxidase or its mimetics can be fulfilled. Horseradish peroxidase has been detected with a detection limit at least two orders of magnitude lower than those obtained by spectrophotometric techniques and traditional membrane-based methods. As an example of peroxidase mimetics, G-quadruplex DNAzymes were probed by the intermediate-sensitive membrane and a label-free thrombin detection protocol was developed based on the catalytic activity of the thrombin-binding G-quadruplex aptamer. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis.

PubMed

Yu, Xiaowen; Yang, Yu-Ping; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia

2017-06-12

The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen-antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.

Green Synthesis of Metallic Nanoparticles via Biological Entities

PubMed Central

Shah, Monaliben; Fawcett, Derek; Sharma, Shashi; Tripathy, Suraj Kumar; Poinern, Gérrard Eddy Jai

2015-01-01

Nanotechnology is the creation, manipulation and use of materials at the nanometre size scale (1 to 100 nm). At this size scale there are significant differences in many material properties that are normally not seen in the same materials at larger scales. Although nanoscale materials can be produced using a variety of traditional physical and chemical processes, it is now possible to biologically synthesize materials via environment-friendly green chemistry based techniques. In recent years, the convergence between nanotechnology and biology has created the new field of nanobiotechnology that incorporates the use of biological entities such as actinomycetes algae, bacteria, fungi, viruses, yeasts, and plants in a number of biochemical and biophysical processes. The biological synthesis via nanobiotechnology processes have a significant potential to boost nanoparticles production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. The aim of this review is to provide an overview of recent trends in synthesizing nanoparticles via biological entities and their potential applications. PMID:28793638

Mimetic finite difference method

NASA Astrophysics Data System (ADS)

Lipnikov, Konstantin; Manzini, Gianmarco; Shashkov, Mikhail

2014-01-01

The mimetic finite difference (MFD) method mimics fundamental properties of mathematical and physical systems including conservation laws, symmetry and positivity of solutions, duality and self-adjointness of differential operators, and exact mathematical identities of the vector and tensor calculus. This article is the first comprehensive review of the 50-year long history of the mimetic methodology and describes in a systematic way the major mimetic ideas and their relevance to academic and real-life problems. The supporting applications include diffusion, electromagnetics, fluid flow, and Lagrangian hydrodynamics problems. The article provides enough details to build various discrete operators on unstructured polygonal and polyhedral meshes and summarizes the major convergence results for the mimetic approximations. Most of these theoretical results, which are presented here as lemmas, propositions and theorems, are either original or an extension of existing results to a more general formulation using polyhedral meshes. Finally, flexibility and extensibility of the mimetic methodology are shown by deriving higher-order approximations, enforcing discrete maximum principles for diffusion problems, and ensuring the numerical stability for saddle-point systems.

Synthesis, characterization and functionalization of silicon nanoparticle based hybrid nanomaterials for photovoltaic and biological applications

NASA Astrophysics Data System (ADS)

Xu, Zejing

Silicon nanoparticles are attractive candidates for biological, photovoltaic and energy storage applications due to their size dependent optoelectronic properties. These include tunable light emission, high brightness, and stability against photo-bleaching relative to organic dyes (see Chapter 1). The preparation and characterization of silicon nanoparticle based hybrid nanomaterials and their relevance to photovoltaic and biological applications are described. The surface-passivated silicon nanoparticles were produced in one step from the reactive high-energy ball milling (RHEBM) of silicon wafers with various organic ligands. The surface structure and optical properties of the passivated silicon nanoparticles were systematically characterized. Fast approaches for purifying and at the same time size separating the silicon nanoparticles using a gravity GPC column were developed. The hydrodynamic diameter and size distribution of these size-separated silicon nanoparticles were determined using GPC and Diffusion Ordered NMR Spectroscopy (DOSY) as fast, reliable alternative approaches to TEM. Water soluble silicon nanoparticles were synthesized by grafting PEG polymers onto functionalized silicon nanoparticles with distal alkyne or azide moieties. The surface-functionalized silicon nanoparticles were produced from the reactive high-energy ball milling (RHEBM) of silicon wafers with a mixture of either 5-chloro-1-pentyne in 1-pentyne or 1,7 octadiyne in 1-hexyne to afford air and water stable chloroalkyl or alkynyl terminated nanoparticles, respectively. Nanoparticles with the ω-chloroalkyl substituents were easily converted to ω-azidoalkyl groups through the reaction of the silicon nanoparticles with sodium azide in DMF. The azido terminated nanoparticles were then grafted with monoalkynyl-PEG polymers using a copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction to afford core-shell silicon nanoparticles with a covalently attached PEG shell. Covalently

Modeling of contact theories for the manipulation of biological micro/nanoparticles in the form of circular crowned rollers based on the atomic force microscope

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

Korayem, M. H.; Khaksar, H.; Taheri, M.

2013-11-14

This article has dealt with the development and modeling of various contact theories for biological nanoparticles shaped as cylinders and circular crowned rollers for application in the manipulation of different biological micro/nanoparticles based on Atomic Force Microscope. First, the effective contact forces were simulated, and their impact on contact mechanics simulation was investigated. In the next step, the Hertz contact model was simulated and compared for gold and DNA nanoparticles with the three types of spherical, cylindrical, and circular crowned roller type contact geometries. Then by reducing the length of the cylindrical section in the circular crowned roller geometry, themore » geometry of the body was made to approach that of a sphere, and the results were compared for DNA nanoparticles. To anticipatory validate the developed theories, the results of the cylindrical and the circular crowned roller contacts were compared with the results of the existing spherical contact simulations. Following the development of these contact models for the manipulation of various biological micro/nanoparticles, the cylindrical and the circular crowned roller type contact theories were modeled based on the theories of Lundberg, Dowson, Nikpur, Heoprich, and Hertz for the manipulation of biological micro/nanoparticles. Then, for a more accurate validation, the results obtained from the simulations were compared with those obtained by the finite element method and with the experimental results available in previous articles. The previous research works on the simulation of nanomanipulation have mainly investigated the contact theories used in the manipulation of spherical micro/nanoparticles. However since in real biomanipulation situations, biological micro/nanoparticles of more complex shapes need to be displaced in biological environments, this article therefore has modeled and compared, for the first time, different contact theories for use in the

Recent Advances in Inorganic Nanoparticle-Based NIR Luminescence Imaging: Semiconductor Nanoparticles and Lanthanide Nanoparticles.

PubMed

Kim, Dokyoon; Lee, Nohyun; Park, Yong Il; Hyeon, Taeghwan

2017-01-18

Several types of nanoparticle-based imaging probes have been developed to replace conventional luminescent probes. For luminescence imaging, near-infrared (NIR) probes are useful in that they allow deep tissue penetration and high spatial resolution as a result of reduced light absorption/scattering and negligible autofluorescence in biological media. They rely on either an anti-Stokes or a Stokes shift process to generate luminescence. For example, transition metal-doped semiconductor nanoparticles and lanthanide-doped inorganic nanoparticles have been demonstrated as anti-Stokes shift-based agents that absorb NIR light through two- or three-photon absorption process and upconversion process, respectively. On the other hand, quantum dots (QDs) and lanthanide-doped nanoparticles that emit in NIR-II range (∼1000 to ∼1350 nm) were suggested as promising Stokes shift-based imaging agents. In this topical review, we summarize and discuss the recent progress in the development of inorganic nanoparticle-based luminescence imaging probes working in NIR range.

Light-sensitive Lipid-based Nanoparticles for Drug Delivery: Design Principles and Future Considerations for Biological Applications

PubMed Central

Yavlovich, Amichai; Smith, Brandon; Gupta, Kshitij; Blumenthal, Robert; Puri, Anu

2011-01-01

Radiation-based therapies aided by nanoparticles have been developed since decades, and can be primarily categorized into two main platforms. First, delivery of payload of photo-reactive drugs (photosensitizers) using the conventional nanoparticles, and second, design and development of photo-triggerable nanoparticles (primarily liposomes) to attain light-assisted on-demand drug delivery. The main focus of this review is to provide an update of the history, current status and future applications of photo-triggerable lipid-based nanoparticles (light-sensitive liposomes). We will begin with a brief overview on the applications of liposomes for delivery of photosensitizers, including the choice of photosensitizers for photodynamic therapy, as well as the currently available light sources (lasers) used for these applications. The main segment of this review will encompass the details on the strategies to develop photo-triggerable designer liposomes for their drug delivery function. The principles underlying the assembly of photoreactive lipids into nanoparticles (liposomes) and photo-triggering mechanisms will be presented. We will also discuss factors that limit the applications of these liposomes for in vivo triggered drug delivery and emerging concepts that may lead to the biologically viable photo-activation strategies. We will conclude with our view point on the future perspectives of light-sensitive liposomes in the clinic. PMID:20939770

Wood mimetic hydrogel beads for enzyme immobilization.

PubMed

Park, Saerom; Kim, Sung Hee; Won, Keehoon; Choi, Joon Weon; Kim, Yong Hwan; Kim, Hyung Joo; Yang, Yung-Hun; Lee, Sang Hyun

2015-01-22

Wood component-based composite hydrogels have potential applications in biomedical fields owing to their low cost, biodegradability, and biocompatibility. The controllable properties of wood mimetic composites containing three major wood components are useful for enzyme immobilization. Here, lipase from Candida rugosa was entrapped in wood mimetic beads containing cellulose, xylan, and lignin by dissolving wood components with lipase in [Emim][Ac], followed by reconstitution. Lipase entrapped in cellulose/xylan/lignin beads in a 5:3:2 ratio showed the highest activity; this ratio is very similar to that in natural wood. The lipase entrapped in various wood mimetic beads showed increased thermal and pH stability. The half-life times of lipase entrapped in cellulose/alkali lignin hydrogel were 31- and 82-times higher than those of free lipase during incubation under denaturing conditions of high temperature and low pH, respectively. Owing to their biocompatibility, biodegradability, and controllable properties, wood mimetic hydrogel beads can be used to immobilize various enzymes for applications in the biomedical, bioelectronic, and biocatalytic fields. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biological Synthesis of Nanoparticles from Plants and Microorganisms.

PubMed

Singh, Priyanka; Kim, Yu-Jin; Zhang, Dabing; Yang, Deok-Chun

2016-07-01

Nanotechnology has become one of the most promising technologies applied in all areas of science. Metal nanoparticles produced by nanotechnology have received global attention due to their extensive applications in the biomedical and physiochemical fields. Recently, synthesizing metal nanoparticles using microorganisms and plants has been extensively studied and has been recognized as a green and efficient way for further exploiting microorganisms as convenient nanofactories. Here, we explore and detail the potential uses of various biological sources for nanoparticle synthesis and the application of those nanoparticles. Furthermore, we highlight recent milestones achieved for the biogenic synthesis of nanoparticles by controlling critical parameters, including the choice of biological source, incubation period, pH, and temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Understanding the Adsorption Interface of Polyelectrolyte Coating on Redox Active Nanoparticles Using Soft Particle Electrokinetics and Its Biological Activity

PubMed Central

2015-01-01

The application of cerium oxide nanoparticles (CNPs) for therapeutic purposes requires a stable dispersion of nanoparticles in a biological environment. The objective of this study is to tailor the properties of polyelectrolyte coated CNPs as a function of molecular weight to achieve a stable and catalytic active dispersion. The coating of CNPs with polyacrylic acid (PAA) has increased the dispersion stability of CNPs and enhanced the catalytic ability. The stability of PAA coating was analyzed using the change in the Gibbs free energy computed by the Langmuir adsorption model. The adsorption isotherms were determined using soft particle electrokinetics which overcomes the challenges presented by other techniques. The change in Gibbs free energy was highest for CNPs coated with PAA of 250 kg/mol indicating the most stable coating. The change in free energy for PAA of 100 kg/mol coated CNPs was 85% lower than the PAA of 250 kg/mol coated CNPs. This significant difference is caused by the strong adsorption of PAA of 100 kg/mol on CNPs. Catalytic activity of PAA-CNPs is assessed by the catalase enzymatic mimetic activity of nanoparticles. The catalase activity was higher for PAA coated CNPs as compared to bare CNPs which indicated preferential adsorption of hydrogen peroxide induced by coating. This indicates that the catalase activity is also affected by the structure of the coating layer. PMID:24673655

Integrated graphene/nanoparticle hybrids for biological and electronic applications

NASA Astrophysics Data System (ADS)

Nguyen, Kim Truc; Zhao, Yanli

2014-05-01

The development of novel graphene/nanoparticle hybrid materials is currently the subject of tremendous research interest. The intrinsic exceptional assets of both graphene (including graphene oxide and reduced graphene oxide) and nanoparticles render their hybrid materials synergic properties that can be useful in various applications. In this feature review, we highlight recent developments in graphene/nanoparticle hybrids and their promising potential in electronic and biological applications. First, the latest advances in synthetic methods for the preparation of the graphene/nanoparticle hybrids are introduced, with the emphasis on approaches to (1) decorate nanoparticles onto two-dimensional graphene and (2) wrap nanoparticles with graphene sheets. The pros and cons of large-scale synthesis are also discussed. Then, the state-of-the-art of graphene/nanoparticle hybrids in electronic and biological applications is reviewed. For electronic applications, we focus on the advantages of using these hybrids in transparent conducting films, as well as energy harvesting and storage. Biological applications, electrochemical biosensing, bioimaging, and drug delivery using the hybrids are showcased. Finally, the future research prospects and challenges in this rapidly developing area are discussed.

Ethylene glycol monolayer protected nanoparticles: synthesis, characterization, and interactions with biological molecules.

PubMed

Zheng, Ming; Li, Zhigang; Huang, Xueying

2004-05-11

The usefulness of the hybrid materials of nanoparticles and biological molecules on many occasions depends on how well one can achieve a rational design based on specific binding and programmable assembly. Nonspecific binding between nanoparticles and biomolecules is one of the major barriers for achieving their utilities in a biological system. In this paper, we demonstrate a new approach to eliminate nonspecific interactions between nanoparticles and biological molecules by shielding the nanoparticle with a monolayer of ethylene glycol. A direct synthesis of di-, tri-, and tetra(ethylene glycol)-protected gold nanoparticles (Au-S-EGn, n = 2, 3, and 4) was achieved under the condition that the water content was optimized in the range of 9-18% in the reaction mixture. With controlled ratio of [HAuCl4]/[EGn-SH] at 2, the synthesized particles have an average diameter of 3.5 nm and a surface plasma resonance band around 510 nm. Their surface structures were confirmed by 1H NMR spectra. These gold nanoparticles are bonded with a uniform monolayer with defined lengths of 0.8, 1.2, and 1.6 nm for Au-S-EG2, Au-S-EG3, and Au-S-EG4, respectively. They have great stabilities in aqueous solutions with a high concentration of electrolytes as well as in organic solvents. Thermogravimetric analysis revealed that the ethylene glycol monolayer coating is ca. 14% of the total nanoparticle weight. Biological binding tests by using ion-exchange chromatography and gel electrophoresis demonstrated that these Au-S-EGn (n = 2, 3, or 4) nanoparticles are free of any nonspecific bindings with various proteins, DNA, and RNA. These types of nanoparticles provide a fundamental starting material for designing hybrid materials composed of metallic nanoparticles and biomolecules.

Distribution and Biological Effects of Nanoparticles in the Reproductive System.

PubMed

Liu, Ying; Li, Hongxia; Xiao, Kai

2016-01-01

Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our

Anti-friction performance of FeS nanoparticle synthesized by biological method

NASA Astrophysics Data System (ADS)

Zhou, Lu Hai; Wei, Xi Cheng; Ma, Zi Jian; Mei, Bin

2017-06-01

FeS nanoparticle is prepared by a biological method. The size, morphology and structure of the FeS nanoparticle are characterized by the means of X-ray diffraction and transmission electron microscopy. The anti-friction behavior of the FeS nanoparticle as a lubricating oil additive is evaluated in the engine oil by using a face-to-face contact mode. The worn surface is characterized by using the scanning electron microscopy and secondary ion mass spectroscopy in order to find the reasons resulting in the reduction of friction coefficient due to the addition of the FeS nanoparticle. The anti-friction mechanism of the FeS nanoparticle is elucidated based on the experimental results.

The Impact of Nanoparticle Surface Chemistry on Biological Systems

NASA Astrophysics Data System (ADS)

Thorn, Angie Sue Morris

The unique properties of nanomaterials, such as their small size and large surface area-to-volume ratios, have attracted tremendous interest in the scientific community over the last few decades. Thus, the synthesis and characterization of many different types of nanoparticles has been well defined and reported on in the literature. Current research efforts have redirected from the basic study of nanomaterial synthesis and their properties to more application-based studies where the development of functionally active materials is necessary. Today such nanoparticle-based systems exist for a range of biomedical applications including imaging, drug delivery and sensors. The inherent properties of the nanomaterial, although important, aren't always ideal for specific applications. In order to optimize nanoparticles for biomedical applications it is often desirable to tune their surface properties. Researchers have shown that these surface properties (such as charge, hydrophobicity, or reactivity) play a direct role in the interactions between nanoparticles and biological systems can be altered by attaching molecules to the surface of nanoparticles. In this work, the effects of physicochemical properties of a wide variety of nanoparticles was investigated using in vitro and in vivo models. For example, copper oxide (CuO) nanoparticles were of interest due to their instability in biological media. These nanoparticles undergo dissolution when in an aqueous environment and tend to aggregate. Therefore, the cytotoxicity of two sizes of CuO NPs was evaluated in cultured cells to develop a better understanding of how these propertied effect toxicity outcomes in biological systems. From these studies, it was determined that CuO NPs are cytotoxic to lung cells in a size-dependent manner and that dissolved copper ions contribute to the cytotoxicity however it is not solely responsible for cell death. Moreover, silica nanoparticles are one of the most commonly used nanomaterials

Caloric Restriction, CR Mimetics, and Healthy Aging in Okinawa: Controversies and Clinical Implications

PubMed Central

Willcox, Bradley J.; Willcox, Donald Craig

2014-01-01

Purpose of Review To examine the role of two nutritional factors implicated in the healthy aging of the Okinawans: caloric restriction (CR); and traditional foods with potential CR-mimetic properties. Recent Findings CR is a research priority for the U.S. National Institute on Aging. However, little is known regarding health effects in humans. Some CR-related outcomes, such as cause-specific mortality and lifespan, are not practical for human clinical trials. Therefore, epidemiological data on older Okinawans, who experienced a CR-like diet for close to half their lives, are of special interest. The nutritional data support mild CR (10–15%) and high consumption of foods that may mimic the biological effects of CR, including sweet potatoes, marine-based carotenoid-rich foods, and turmeric. Phenotypic evidence is consistent with CR (including short stature, low body weight, lean BMI), less age-related chronic disease (including cardiovascular diseases, cancer, and dementia) and longer lifespan (mean and maximum). Summary Both CR and traditional Okinawan functional foods with CR-mimetic properties likely had roles in the extended healthspan and lifespan of the Okinawans. More research is needed on health consequences of CR and foods with CR-mimetic properties to identify possible nutritional interventions for healthy aging. PMID:24316687

Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic

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

Jalilov, Almaz S.; Nilewski, Lizanne G.; Berka, Vladimir

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG–HCCs), will afford important insights into the highly efficient activity of PEG–HCCs and their graphitic analogues. PEGylated perylene diimides (PEGn–PDI) serve as well-defined molecular analogues of PEG–HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied. PEGn–PDIs have two reversible reductionmore » peaks, which are more positive than the oxidation peak of superoxide (O2•–). This is similar to the reduction peak of the HCCs. Thus, as with PEG–HCCs, PEGn–PDIs are also strong single-electron oxidants of O2•–. Furthermore, reduced PEGn–PDI, PEGn–PDI•–, in the presence of protons, was shown to reduce O2•– to H2O2 to complete the catalytic cycle in this SOD analogue. The kinetics of the conversion of O2•– to O2 and H2O2 by PEG8–PDI was measured using freeze-trap EPR experiments to provide a turnover number of 133 s–1; the similarity in kinetics further supports that PEG8–PDI is a true SOD mimetic. Finally, PDIs can be used as catalysts in the electrochemical oxygen reduction reaction in water, which proceeds by a two-electron process with the production of H2O2, mimicking graphene oxide nanoparticles that are otherwise difficult to study spectroscopically.« less

Design and synthesis of type-III mimetics of ShK toxin

NASA Astrophysics Data System (ADS)

Baell, Jonathan B.; Harvey, Andrew J.; Norton, Raymond S.

2002-04-01

ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining.

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy

PubMed Central

Zhang, Mengyuan; He, Jianhua; Jiang, Cuiping; Zhang, Wenli; Yang, Yun; Wang, Zhiyu; Liu, Jianping

2017-01-01

Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core–shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal. It contained a biodegradable poly (lactic-co-glycolic acid) (PLGA) core within a lipid bilayer, and apolipoprotein A-I (apoA-I) absorbing on the lipid bilayer was covalently decorated with HA. The covalent HA coating with superior stability and greater shielding was favorable for not only minimizing the liver uptake but also facilitating the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors in atherosclerotic plaques. The ultimate iMΦ homing was achieved via apoA-I after HA coating degraded by hyaluronidase (HAase) (abundant in atherosclerotic plaque). The multistage-targeting mechanism was revealed on the established injured endothelium–macrophage co-culture dynamic system. Upon treatment with HAase in vitro, the nanoparticle HA-(C)-PLGA-rHDL exhibited a greater cholesterol efflux capacity compared with conventional rHDL (2.43-fold). Better targeting efficiency toward iMΦ and attenuated liver accumulation were further proved by results from ex vivo imaging and iMΦ-specific fluorescence localization. Ultimately, HA-(C)-PLGA-rHDL loaded with simvastatin realized the most potent anti-atherogenic efficacies in model animals over other preparations. Thus, the HAase-responsive HDL-mimetic nanoparticle was shown in this study to be a promising nanocarrier for anti-atherogenic therapy, in the light of efficient iMΦ-targeted drug delivery and excellent function of

Principles of nanoparticle design for overcoming biological barriers to drug delivery

PubMed Central

Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

2016-01-01

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

Instabilities in mimetic matter perturbations

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

Firouzjahi, Hassan; Gorji, Mohammad Ali; Mansoori, Seyed Ali Hosseini, E-mail: firouz@ipm.ir, E-mail: gorji@ipm.ir, E-mail: shosseini@shahroodut.ac.ir, E-mail: shossein@ipm.ir

2017-07-01

We study cosmological perturbations in mimetic matter scenario with a general higher derivative function. We calculate the quadratic action and show that both the kinetic term and the gradient term have the wrong sings. We perform the analysis in both comoving and Newtonian gauges and confirm that the Hamiltonians and the associated instabilities are consistent with each other in both gauges. The existence of instabilities is independent of the specific form of higher derivative function which generates gradients for mimetic field perturbations. It is verified that the ghost instability in mimetic perturbations is not associated with the higher derivative instabilitiesmore » such as the Ostrogradsky ghost.« less

Instabilities in mimetic matter perturbations

NASA Astrophysics Data System (ADS)

Firouzjahi, Hassan; Gorji, Mohammad Ali; Mansoori, Seyed Ali Hosseini

2017-07-01

We study cosmological perturbations in mimetic matter scenario with a general higher derivative function. We calculate the quadratic action and show that both the kinetic term and the gradient term have the wrong sings. We perform the analysis in both comoving and Newtonian gauges and confirm that the Hamiltonians and the associated instabilities are consistent with each other in both gauges. The existence of instabilities is independent of the specific form of higher derivative function which generates gradients for mimetic field perturbations. It is verified that the ghost instability in mimetic perturbations is not associated with the higher derivative instabilities such as the Ostrogradsky ghost.

Identification of nanoparticles and nanosystems in biological matrices with scanning probe microscopy.

PubMed

Angeloni, Livia; Reggente, Melania; Passeri, Daniele; Natali, Marco; Rossi, Marco

2018-04-17

Identification of nanoparticles and nanosystems into cells and biological matrices is a hot research topic in nanobiotechnologies. Because of their capability to map physical properties (mechanical, electric, magnetic, chemical, or optical), several scanning probe microscopy based techniques have been proposed for the subsurface detection of nanomaterials in biological systems. In particular, atomic force microscopy (AFM) can be used to reveal stiff nanoparticles in cells and other soft biomaterials by probing the sample mechanical properties through the acquisition of local indentation curves or through the combination of ultrasound-based methods, like contact resonance AFM (CR-AFM) or scanning near field ultrasound holography. Magnetic force microscopy can detect magnetic nanoparticles and other magnetic (bio)materials in nonmagnetic biological samples, while electric force microscopy, conductive AFM, and Kelvin probe force microscopy can reveal buried nanomaterials on the basis of the differences between their electric properties and those of the surrounding matrices. Finally, scanning near field optical microscopy and tip-enhanced Raman spectroscopy can visualize buried nanostructures on the basis of their optical and chemical properties. Despite at a still early stage, these methods are promising for detection of nanomaterials in biological systems as they could be truly noninvasive, would not require destructive and time-consuming specific sample preparation, could be performed in vitro, on alive samples and in water or physiological environment, and by continuously imaging the same sample could be used to dynamically monitor the diffusion paths and interaction mechanisms of nanomaterials into cells and biological systems. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2018 Wiley Periodicals, Inc.

Magnetic nanoparticles as potential candidates for biomedical and biological applications.

PubMed

Zeinali Sehrig, Fatemeh; Majidi, Sima; Nikzamir, Nasrin; Nikzamir, Nasim; Nikzamir, Mohammad; Akbarzadeh, Abolfazl

2016-05-01

Magnetic iron oxide nanoparticles have become the main candidates for biomedical and biological applications, and the application of small iron oxide nanoparticles in in vitro diagnostics has been practiced for about half a century. Magnetic nanoparticles (MNPs), in combination with an external magnetic field and/or magnetizable grafts, allow the delivery of particles to the chosen target area, fix them at the local site while the medication is released, and act locally. In this review, we focus mostly on the potential use of MNPs for biomedical and biotechnological applications, and the improvements made in using these nanoparticles (NPs) in biological applications.

Interaction of silver nanoparticles with biological objects: antimicrobial properties and toxicity for the other living organisms

NASA Astrophysics Data System (ADS)

Egorova, E. M.

2011-04-01

This paper presents several examples of the biological effects of small-sized silver nanoparticles (10.5±3.5nm) observed in experiments on bacteria, slim mold, unicellular alga and plant seeds. The nanoparticles were prepared by the biochemical synthesis, based on the reduction of metal ions in reverse vicelles by biological reductants - natural plant pigments (flavonoids). It is found that, except for the plant seeds, silver nanoparticles (SNP) act as a strong toxic agent, both in water solution and as part of liquid-phase material. It is shown also that the biological action of silver nanoparticles can not be reduced to the toxic action of silver ions in equivalent concentrations or to that of the surfactant (the SNP stabilizer) present in the SNP water solution. Possible SNP applications are suggested.

Black hole solutions in mimetic Born-Infeld gravity

NASA Astrophysics Data System (ADS)

Chen, Che-Yu; Bouhmadi-López, Mariam; Chen, Pisin

2018-01-01

The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. We find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularity is found to be infinite.

Black hole solutions in mimetic Born-Infeld gravity.

PubMed

Chen, Che-Yu; Bouhmadi-López, Mariam; Chen, Pisin

2018-01-01

The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. We find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularity is found to be infinite.

Black hole solutions in mimetic Born-Infeld gravity

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

Chen, Che-Yu; Bouhmadi-López, Mariam; Chen, Pisin

The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. Here, we find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularitymore » is found to be infinite.« less

Black hole solutions in mimetic Born-Infeld gravity

DOE PAGES

Chen, Che-Yu; Bouhmadi-López, Mariam; Chen, Pisin

2018-01-23

The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. Here, we find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularitymore » is found to be infinite.« less

Growth of well-defined metal and oxide nanoparticles on biological surfaces

NASA Astrophysics Data System (ADS)

Tsukruk, Vladimir

2009-03-01

We present a brief overview of our recent studies in the field of bio-enabled surface-mediated growth of inorganic nanoparticles at room temperature and ambient conditions. We demonstrate that all titania, gold, and silver nanoparticles can be grown with relatively monodisperse diameter within 4-6 nm surrounded by biological shells of 1-2 nm thick. As biological templates we utilized ultrathin, molecular uniform and micropatterned surface layers of two different proteins: silk fibroin (for growth of gold and silver nanoparticles) and silaffin (for growth of titania nanoparticles). To identify the grown nanophases and chemical composition/secondary structure of biological templates we applied combined AFM, SEM, TEM, XPS, SERS, UV-vis, and ATR-FTIR techniques.

Antibody mimetics: promising complementary agents to animal-sourced antibodies.

PubMed

Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

2016-01-01

Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed.

Large-scale structure in mimetic Horndeski gravity

NASA Astrophysics Data System (ADS)

Arroja, Frederico; Okumura, Teppei; Bartolo, Nicola; Karmakar, Purnendu; Matarrese, Sabino

2018-05-01

In this paper, we propose to use the mimetic Horndeski model as a model for the dark universe. Both cold dark matter (CDM) and dark energy (DE) phenomena are described by a single component, the mimetic field. In linear theory, we show that this component effectively behaves like a perfect fluid with zero sound speed and clusters on all scales. For the simpler mimetic cubic Horndeski model, if the background expansion history is chosen to be identical to a perfect fluid DE (PFDE) then the mimetic model predicts the same power spectrum of the Newtonian potential as the PFDE model with zero sound speed. In particular, if the background is chosen to be the same as that of LCDM, then also in this case the power spectrum of the Newtonian potential in the mimetic model becomes indistinguishable from the power spectrum in LCDM on linear scales. A different conclusion may be found in the case of non-adiabatic perturbations. We also discuss the distinguishability, using power spectrum measurements from LCDM N-body simulations as a proxy for future observations, between these mimetic models and other popular models of DE. For instance, we find that if the background has an equation of state equal to ‑0.95 then we will be able to distinguish the mimetic model from the PFDE model with unity sound speed. On the other hand, it will be hard to do this distinction with respect to the LCDM model.

Synthesis and evaluation of di- and trimeric hydroxylamine-based β-(1→3)-glucan mimetics.

PubMed

Ferry, Angélique; Malik, Gaëlle; Guinchard, Xavier; Vĕtvička, Václav; Crich, David

2014-10-22

Di- and trimeric hydroxylamine-based mimetics of β-(1→3)-glucans have been accessed by an asymmetric synthesis route featuring an iterative double ring-closing reductive amination reaction. These oligomeric hydroxylamines are demonstrated to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-dectin-1 antibodies, respectively, and to stimulate phagocytosis, all in a linkage-dependent manner suggestive of binding to the lectin domains of complement receptor 3 (CR3) and dectin-1. The ability of these relatively short mimetics to bind to CR3 and dectin-1, as compared to the greater degree of polymerization required in β-(1→3)-glucans, is discussed in terms of the increased hydrophobicity of the α-face on replacement of the glycosidic bond by the hydroxylamine linkage.

Fabrication of hierarchical feather-mimetic polymer nanofibres

NASA Astrophysics Data System (ADS)

Ouyang, Shenshen; Wang, Tao; Zhong, Longgang; Peng, Meiling; Yao, Juming; Wang, Sheng

2018-01-01

In this study, hierarchically feather-mimetic structures formed of poly(m-phenylene isophthalamide) (PMIA) nanofibres were prepared by electrospinning and subsequent crystallisation for superwettability applications. X-ray diffraction measurementsand scanning electron microscopy show that a feather-mimetic structure of crystallised nanoflakes was formed following a hydrothermal treatment process. The nanoflakes formed a nanosized fine texture on top of a coarser-textured membrane, which greatly improved the membrane roughness and yielded a hierarchical topography. After fluorination, the membrane exhibited superamphiphobicity, with surface contact angles of 151° and 136° for water and hexadecane, respectively. The method provides new insight for the design and development of functional bionic membranes based on PMIA.

Quantification of nanoparticle endocytosis based on double fluorescent pH-sensitive nanoparticles.

PubMed

Kurtz-Chalot, Andréa; Klein, Jean-Philippe; Pourchez, Jérémie; Boudard, Delphine; Bin, Valérie; Sabido, Odile; Marmuse, Laurence; Cottier, Michèle; Forest, Valérie

2015-04-01

Amorphous silica is a particularly interesting material because of its inertness and chemical stability. Silica nanoparticles have been recently developed for biomedical purposes but their innocuousness must be carefully investigated before clinical use. The relationship between nanoparticles physicochemical features, their uptake by cells and their biological activity represents a crucial issue, especially for the development of nanomedicine. This work aimed at adapting a method for the quantification of nanoparticle endocytosis based on pH-sensitive and double fluorescent particles. For that purpose, silica nanoparticles containing two fluorophores: FITC and pHrodo(TM) were developed, their respective fluorescence emission depends on the external pH. Indeed, FITC emits a green fluorescence at physiological pH and pHrodo(TM) emits a red fluorescence which intensity increased with acidification. Therefore, nanoparticles remained outside the cells could be clearly distinguished from nanoparticles uptaken by cells as these latter could be spotted inside cellular acidic compartments (such as phagolysosomes, micropinosomes…). Using this model, the endocytosis of 60 nm nanoparticles incubated with the RAW 264.7 macrophages was quantified using time-lapse microscopy and compared to that of 130 nm submicronic particles. The amount of internalized particles was also evaluated by fluorimetry. The biological impact of the particles was also investigated in terms of cytotoxicity, pro-inflammatory response and oxidative stress. Results clearly demonstrated that nanoparticles were more uptaken and more reactive than submicronic particles. Moreover, we validated a method of endocytosis quantification.

Anisotropic mimetic cosmology

NASA Astrophysics Data System (ADS)

Abbassi, M. H.; Jozani, A.; Sepangi, H. R.

2018-06-01

We consider a mimetic set up in which the mimetic scalar is coupled to a vector field. It is shown that such a field with a timelike component does not contribute to the background equations and yet produces healthy isocurvature perturbations with respect to ghost and gradient instabilities in spite of the absence of any propagating curvature perturbations at the level of the quadratic action. We then consider a vector field with spacelike components, which leads to an anisotropic Bianchi universe, and show that the ghost and gradient instabilities are absent in the limit of high momenta and that the propagating curvature perturbations have healthy UV behavior.

Biological synthesis of platinum nanoparticles with apoferritin.

PubMed

Deng, Q Y; Yang, B; Wang, J F; Whiteley, C G; Wang, X N

2009-10-01

A novel biological method for the synthesis of platinum nanoparticles using the horse spleen apoferritin (HSAF) is reported. When HSAF was incubated with K(2)PtCl(6) at 23 degrees C) for 48 h followed by subsequent reduction with NaBH(4) it resulted in the formation of spherical platinum nanoparticles, size 4.7 +/- 0.9 nm, with narrow particle size distribution confirmed by transmission electron microscopy and energy dispersive X-ray analysis. As the initial platinum concentration increased through 0.155, 0.31, 0.465 to 0.62 mM the efficiency of its removal from solution by the apoferritin was 99, 99, 84 and 71% respectively. The maximum uptake of platinum salt per mM apoferritin was estimated at 12.7 mmol l(-1) h(-1). These results clearly indicate that the HSAF protein cage can successfully serve as a suitable size-constrained support matrix for the biological synthesis of platinum nanoparticles.

Real-time Monitoring of Nanoparticle-based Therapeutics: A Review.

PubMed

Han, Qingqing; Niu, Meng; Wu, Qirun; Zhong, Hongshan

2018-01-01

With the development of nanomaterials, nanoparticle-based therapeutics have found increasing application in various fields, including clinical and basic medicine. Real-time monitoring of nanoparticle-based therapeutics is considered critical to both pharmacology and pharmacokinetics. In this review, we discuss the different methods of real-time monitoring of nanoparticle-based therapeutics comprising different types of nanoparticle carriers, such as metal nanoparticles, inorganic nonmetallic nanoparticles, biodegradable polymer nanoparticles, and biological nanoparticles. In the light of examples and analyses, we conclude that the methods of analysis of the four types of nanoparticle carriers are commonly used methods and mostly not necessary. Under most circumstances, real-time monitoring differs according to nanoparticle type, drugs, diseases, and surroundings. With technology development and advanced researches, there have been increasing measures to track the real-time changes in nanoparticles, and this has led to great progress in pharmacology and therapeutics. However, future studies are warranted to determine the accuracy, applicability, and practicability of different technologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter?

PubMed

Vazquez-Muñoz, Roberto; Borrego, Belen; Juárez-Moreno, Karla; García-García, Maritza; Mota Morales, Josué D; Bogdanchikova, Nina; Huerta-Saquero, Alejandro

2017-07-05

Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike. Copyright © 2017 Elsevier B.V. All rights reserved.

Silver Nanoparticle Storage Stability in Aqueous and Biological Media

DTIC Science & Technology

2015-06-22

silver nanoparticle stability from the point of synthesis to the point of testing. The recommended conditions of water storage at 4°C protected from... silver nanoparticle formulation for fabrication. (Report No. 2014-73). 13 Métraux, G. S. & Mirkin, C. A. Rapid thermal synthesis of silver ...NAVAL MEDICAL RESEARCH UNIT SAN ANTONIO SILVER NANOPARTICLE STORAGE STABILITY IN AQUEOUS AND BIOLOGICAL MEDIA NATALIE A

Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment.

PubMed

Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

2016-04-11

Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment.

Fabrication and characterization of biological tissue phantoms with embedded nanoparticles

NASA Astrophysics Data System (ADS)

Skaptsov, A. A.; Ustalkov, S. O.; Mohammed, A. H. M.; Savenko, O. A.; Novikova, A. S.; Kozlova, E. A.; Kochubey, V. I.

2017-11-01

Phantoms are imitations of biological tissue, which are used for modelling of the light propagation in biological tissues. Carrying out any biophysical experiments requires an indispensable constancy of the initial experiment conditions. The use of solid undegradable phantoms is the basis to obtain reliable reproducible experimental results. The fabrication of biological tissues phantoms containing high absorbance or fluorescence nanoparticles and corresponding to specific mechanical, optical properties is an actual task. This work describes development, fabrication and characterization of such solid tissue phantoms with embedded CdSe/ZnS quantum dots, gold and upconversion nanoparticles. Luminescence of samples with CdSe/ZnS quantum dots and upconversion nanoparticles were recorded. A sample of gold nanorods was analyzed using thermal gravimetric analysis. It can be concluded that the samples are well suited for experiments on laser thermolysis.

Immunopharmacology of lipid A mimetics.

PubMed

Bowen, William S; Gandhapudi, Siva K; Kolb, Joseph P; Mitchell, Thomas C

2013-01-01

The structural core of bacterial lipopolysaccharide, lipid A, has played a role in medicine since the 1890s when William Coley sought to harness its immunostimulatory properties in the form of a crude bacterial extract. Recent decades have brought remarkable clarity to the structure of lipid A and the multicomponent endotoxin receptor system that evolved to detect it. A range of therapeutically useful versions of lipid A now exists, including preparations of detoxified lipid A, synthetic copies of naturally occurring biological intermediates such as lipid IVa, and synthetic mimetics. These agents are finding use as vaccine adjuvants, antagonists and immunostimulants whose structural features have been refined to potentiate efficacy while decreasing the risk of inflammatory side effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Silica nanoparticle stability in biological media revisited.

PubMed

Yang, Seon-Ah; Choi, Sungmoon; Jeon, Seon Mi; Yu, Junhua

2018-01-09

The stability of silica nanostructure in the core-silica shell nanomaterials is critical to understanding the activity of these nanomaterials since the exposure of core materials due to the poor stability of silica may cause misinterpretation of experiments, but unfortunately reports on the stability of silica have been inconsistent. Here, we show that luminescent silver nanodots (AgNDs) can be used to monitor the stability of silica nanostructures. Though relatively stable in water and phosphate buffered saline, silica nanoparticles are eroded by biological media, leading to the exposure of AgNDs from AgND@SiO 2 nanoparticles and the quenching of nanodot luminescence. Our results reveal that a synergistic effect of organic compounds, particularly the amino groups, accelerates the erosion. Our work indicates that silica nanostructures are vulnerable to cellular medium and it may be possible to tune the release of drug molecules from silica-based drug delivery vehicles through controlled erosion.

Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

PubMed Central

Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

2010-01-01

In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We

Interface of physics and biology: engineering virus-based nanoparticles for biophotonics.

PubMed

Wen, Amy M; Infusino, Melissa; De Luca, Antonio; Kernan, Daniel L; Czapar, Anna E; Strangi, Giuseppe; Steinmetz, Nicole F

2015-01-21

Virus-based nanoparticles (VNPs) have been used for a wide range of applications, spanning basic materials science and translational medicine. Their propensity to self-assemble into precise structures that offer a three-dimensional scaffold for functionalization has led to their use as optical contrast agents and related biophotonics applications. A number of fluorescently labeled platforms have been developed and their utility in optical imaging demonstrated, yet their optical properties have not been investigated in detail. In this study, two VNPs of varying architectures were compared side-by-side to determine the impact of dye density, dye localization, conjugation chemistry, and microenvironment on the optical properties of the probes. Dyes were attached to icosahedral cowpea mosaic virus (CPMV) and rod-shaped tobacco mosaic virus (TMV) through a range of chemistries to target particular side chains displayed at specific locations around the virus. The fluorescence intensity and lifetime of the particles were determined, first using photochemical experiments on the benchtop, and second in imaging experiments using tissue culture experiments. The virus-based optical probes were found to be extraordinarily robust under ultrashort, pulsed laser light conditions with a significant amount of excitation energy, maintaining structural and chemical stability. The most effective fluorescence output was achieved through dye placement at optimized densities coupled to the exterior surface avoiding conjugated ring systems. Lifetime measurements indicate that fluorescence output depends not only on spacing the fluorophores, but also on dimer stacking and configurational changes leading to radiationless relaxation-and these processes are related to the conjugation chemistry and nanoparticle shape. For biological applications, the particles were also examined in tissue culture, from which it was found that the optical properties differed from those found on the benchtop due

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

PubMed Central

Choi, Soo-Jin; Choy, Jin-Ho

2014-01-01

Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle–protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins. PMID:25565844

Effects of magnetic cobalt ferrite nanoparticles on biological and artificial lipid membranes

PubMed Central

Drašler, Barbara; Drobne, Damjana; Novak, Sara; Valant, Janez; Boljte, Sabina; Otrin, Lado; Rappolt, Michael; Sartori, Barbara; Iglič, Aleš; Kralj-Iglič, Veronika; Šuštar, Vid; Makovec, Darko; Gyergyek, Sašo; Hočevar, Matej; Godec, Matjaž; Zupanc, Jernej

2014-01-01

Background The purpose of this work is to provide experimental evidence on the interactions of suspended nanoparticles with artificial or biological membranes and to assess the possibility of suspended nanoparticles interacting with the lipid component of biological membranes. Methods 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid vesicles and human red blood cells were incubated in suspensions of magnetic bare cobalt ferrite (CoFe2O4) or citric acid (CA)-adsorbed CoFe2O4 nanoparticles dispersed in phosphate-buffered saline and glucose solution. The stability of POPC giant unilamellar vesicles after incubation in the tested nanoparticle suspensions was assessed by phase-contrast light microscopy and analyzed with computer-aided imaging. Structural changes in the POPC multilamellar vesicles were assessed by small angle X-ray scattering, and the shape transformation of red blood cells after incubation in tested suspensions of nanoparticles was observed using scanning electron microscopy and sedimentation, agglutination, and hemolysis assays. Results Artificial lipid membranes were disturbed more by CA-adsorbed CoFe2O4 nanoparticle suspensions than by bare CoFe2O4 nanoparticle suspensions. CA-adsorbed CoFe2O4-CA nanoparticles caused more significant shape transformation in red blood cells than bare CoFe2O4 nanoparticles. Conclusion Consistent with their smaller sized agglomerates, CA-adsorbed CoFe2O4 nanoparticles demonstrate more pronounced effects on artificial and biological membranes. Larger agglomerates of nanoparticles were confirmed to be reactive against lipid membranes and thus not acceptable for use with red blood cells. This finding is significant with respect to the efficient and safe application of nanoparticles as medicinal agents. PMID:24741305

Biological applications of gold nanoparticles.

PubMed

Shah, Monic; Badwaik, Vivek D; Dakshinamurthy, Rajalingam

2014-01-01

This article reviews some of the recent biological applications of gold nanoparticles (GNPs) which have been discovered lately by individual studies all around the world. GNPs have emerged as a promising candidates for various biological applications due to their unique physical properties (size and shape dependent), excellent biocompatibility, facile synthesis, ease of bioconjugation, etc. This review starts with a brief introduction about nanotechnology followed by an insight into the history, emergence, and enhanced properties of various gold nanostructures, which form the basis for their numerous biomedical applications. In addition, a brief overview on some of the commonly used fabrication techniques for synthesizing GNPs is also discussed. Finally, a miscellany of the latest biological applications of GNPs, such as cancer diagnostics and therapy, biological probes, drug delivery, gene delivery, vaccine preparation, brain implants, artificial skin, sterilization system, and improving electrical signaling in the heart, published in different articles in reputed journals are highlighted.

Healthy imperfect dark matter from effective theory of mimetic cosmological perturbations

NASA Astrophysics Data System (ADS)

Hirano, Shin'ichi; Nishi, Sakine; Kobayashi, Tsutomu

2017-07-01

We study the stability of a recently proposed model of scalar-field matter called mimetic dark matter or imperfect dark matter. It has been known that mimetic matter with higher derivative terms suffers from gradient instabilities in scalar perturbations. To seek for an instability-free extension of imperfect dark matter, we develop an effective theory of cosmological perturbations subject to the constraint on the scalar field's kinetic term. This is done by using the unifying framework of general scalar-tensor theories based on the ADM formalism. We demonstrate that it is indeed possible to construct a model of imperfect dark matter which is free from ghost and gradient instabilities. As a side remark, we also show that mimetic F(Script R) theory is plagued with the Ostrogradsky instability.

Progress of Mimetic Enzymes and Their Applications in Chemical Sensors.

PubMed

Yang, Bin; Li, Jianping; Deng, Huan; Zhang, Lianming

2016-11-01

The need to develop innovative and reformative approaches to synthesize chemical sensors has increased in recent years because of demands for selectivity, stability, and reproducibility. Mimetic enzymes provide an efficient and convenient method for chemical sensors. This review summarizes the application of mimetic enzymes in chemical sensors. Mimetic enzymes can be classified into five categories: hydrolases, oxidoreductases, transferases, isomerases, and induced enzymes. Potential and recent applications of mimetic enzymes in chemical sensors are reviewed in detail, and the outlook of profound development has been illustrated.

Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor

DOE PAGES

Zha, R. Helen; Sur, Shantanu; Boekhoven, Job; ...

2014-11-08

Aberrant angiogenesis plays a large role in pathologies ranging from tumor growth to macular degeneration. Anti-angiogenic proteins have thus come under scrutiny as versatile, potent therapeutics but face problems with purification and tissue retention. We report here on the synthesis of supramolecular nanostructures that mimic the anti-angiogenic activity of maspin, a class II tumor suppressor protein. These maspin-mimetic nanostructures are formed via self-assembly of small peptide amphiphiles containing the g-helix motif of maspin. Using tubulogenesis assays with human umbilical vein endothelial cells, we demonstrate that maspin-mimetic nanostructures show anti-angiogenic activity at concentrations that are significantly lower than those necessary formore » the g-helix peptide. Furthermore, in vivo assays in the chick chorioallantoic membrane show maspin-mimetic nanostructures to be effective over controls at inhibiting angiogenesis. Thus, in conclusion, the nanostructures investigated here offer an attractive alternative to the use of anti-angiogenic recombinant proteins in the treatment of cancer or other diseases involving abnormal blood vessel formation.« less

Innovative molecular-based fluorescent nanoparticles for multicolor single particle tracking in cells

NASA Astrophysics Data System (ADS)

Daniel, Jonathan; Godin, Antoine G.; Palayret, Matthieu; Lounis, Brahim; Cognet, Laurent; Blanchard-Desce, Mireille

2016-03-01

Based on an original molecular-based design, we present bright and photostable fluorescent organic nanoparticles (FONs) showing excellent colloidal stability in various aqueous environments. Complementary near-infrared emitting and green emitting FONs were prepared using a simple, fast and robust protocol. Both types of FONs could be simultaneously imaged at the single-particle level in solution as well as in biological environments using a monochromatic excitation and a dual-color fluorescence microscope. No evidence of acute cytotoxicity was found upon incubation of live cells with mixed solutions of FONs, and both types of nanoparticles were found internalized in the cells where their motion could be simultaneously tracked at video-rate up to minutes. These fluorescent organic nanoparticles open a novel non-toxic alternative to existing nanoparticles for imaging biological structures, compatible with live-cell experiments and specially fitted for multicolor single particle tracking.

Biological Mechanism of Silver Nanoparticle Toxicity

NASA Astrophysics Data System (ADS)

Armstrong, Najealicka Nicole

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further

Cosmological perturbations in mimetic Horndeski gravity

NASA Astrophysics Data System (ADS)

Arroja, Frederico; Bartolo, Nicola; Karmakar, Purnendu; Matarrese, Sabino

2016-04-01

We study linear scalar perturbations around a flat FLRW background in mimetic Horndeski gravity. In the absence of matter, we show that the Newtonian potential satisfies a second-order differential equation with no spatial derivatives. This implies that the sound speed for scalar perturbations is exactly zero on this background. We also show that in mimetic G3 theories the sound speed is equally zero. We obtain the equation of motion for the comoving curvature perturbation (first order differential equation) and solve it to find that the comoving curvature perturbation is constant on all scales in mimetic Horndeski gravity. We find solutions for the Newtonian potential evolution equation in two simple models. Finally we show that the sound speed is zero on all backgrounds and therefore the system does not have any wave-like scalar degrees of freedom.

Synthesis of silver nanoparticles: chemical, physical and biological methods

PubMed Central

Iravani, S.; Korbekandi, H.; Mirmohammadi, S.V.; Zolfaghari, B.

2014-01-01

Silver nanoparticles (NPs) have been the subjects of researchers because of their unique properties (e.g., size and shape depending optical, antimicrobial, and electrical properties). A variety of preparation techniques have been reported for the synthesis of silver NPs; notable examples include, laser ablation, gamma irradiation, electron irradiation, chemical reduction, photochemical methods, microwave processing, and biological synthetic methods. This review presents an overview of silver nanoparticle preparation by physical, chemical, and biological synthesis. The aim of this review article is, therefore, to reflect on the current state and future prospects, especially the potentials and limitations of the above mentioned techniques for industries. PMID:26339255

Modulation of surface structure and catalytic properties of cerium oxide nanoparticles by thermal and microwave synthesis techniques

NASA Astrophysics Data System (ADS)

He, Jian; Zhou, Lan; Liu, Jie; Yang, Lu; Zou, Ling; Xiang, Junyu; Dong, Shiwu; Yang, Xiaochao

2017-04-01

Cerium oxide nanoparticles (CNPs) have been intensively explored for biomedical applications in recent few years due to the versatile enzyme mimetic activities of the nanoparticles. However, the control of CNPs quality through the optimization of synthesis conditions remains largely unexplored as most of the previous studies only focus on utilizing the catalytic activities of the nanoparticles. In the present study, CNPs with size about 5 nm were synthesized by thermal decomposition method using traditional convective heating and recently developed microwave irradiation as heating source. The quality of CNPs synthesized by the two heating manner was evaluated. The CNPs synthesized by convective heating were slightly smaller than that synthesized by microwave irradiation heating. The cores of the CNPs synthesized by the two heating manner have similar crystal structure. While the surface subtle structures of the CNPs synthesized by two heating manner were different. The CNPs synthesized by microwave irradiation have more surface reactive hot spot than that synthesized by convective heating as the nanoparticles responded more actively to the redox environment variation. This difference resulted in the higher superoxide dismutase (SOD) mimetic activity of CNPs synthesized by microwave irradiation heating than that of the convective heating. Preliminary experiments indicated that the CNPs synthesized by microwave irradiation heating could better protect cells from oxidative stress due to the higher SOD mimetic activity of the nanoparticles.

Bio-based polyurethane for tissue engineering applications: How hydroxyapatite nanoparticles influence the structure, thermal and biological behavior of polyurethane composites.

PubMed

Gabriel, Laís P; Santos, Maria Elizabeth M Dos; Jardini, André L; Bastos, Gilmara N T; Dias, Carmen G B T; Webster, Thomas J; Maciel Filho, Rubens

2017-01-01

In this work, thermoset polyurethane composites were prepared by the addition of hydroxyapatite nanoparticles using the reactants polyol polyether and an aliphatic diisocyanate. The polyol employed in this study was extracted from the Euterpe oleracea Mart. seeds from the Amazon Region of Brazil. The influence of hydroxyapatite nanoparticles on the structure and morphology of the composites was studied using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), the structure was evaluated by Fourier transform infrared spectroscopy (FT-IR), thermal properties were analyzed by thermogravimetry analysis (TGA), and biological properties were studied by in vitro and in vivo studies. It was found that the addition of HA nanoparticles promoted fibroblast adhesion while in vivo investigations with histology confirmed that the composites promoted connective tissue adherence and did not induce inflammation. In this manner, this study supports the further investigation of bio-based, polyurethane/hydroxyapatite composites as biocompatible scaffolds for numerous tissue engineering applications. Copyright © 2016 Elsevier Inc. All rights reserved.

A modular synthesis of teraryl-based α-helix mimetics, part 1: Synthesis of core fragments with two electronically differentiated leaving groups.

PubMed

Peters, Martin; Trobe, Melanie; Tan, Hao; Kleineweischede, Rolf; Breinbauer, Rolf

2013-02-11

Teraryl-based α-helix mimetics have proven to be useful compounds for the inhibition of protein-protein interactions (PPI). We have developed a modular and flexible approach for the synthesis of teraryl-based α-helix mimetics. Central to our strategy is the use of a benzene core unit featuring two leaving groups of differentiated reactivity in the Pd-catalyzed cross-coupling used for terphenyl assembly. With the halogen/diazonium route and the halogen/triflate route, two strategies have successfully been established. The synthesis of core building blocks with aliphatic (Ala, Val, Leu, Ile), aromatic (Phe), polar (Cys, Lys), hydrophilic (Ser, Gln), and acidic (Glu) amino acid side chains are reported. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biological synthesis of nanoparticles in biofilms.

PubMed

Tanzil, Abid H; Sultana, Sujala T; Saunders, Steven R; Shi, Liang; Marsili, Enrico; Beyenal, Haluk

2016-12-01

The biological synthesis of nanoparticles (NPs) by bacteria and biofilms via extracellular redox reactions has received attention because of the minimization of harmful chemicals, low cost, and ease of culturing and downstream processing. Bioreduction mechanisms vary across bacteria and growth conditions, which leads to various sizes and shapes of biosynthesized NPs. NP synthesis in biofilms offers additional advantages, such as higher biomass concentrations and larger surface areas, which can lead to more efficient and scalable biosynthesis. Although biofilms have been used to produce NPs, the mechanistic details of NP formation are not well understood. In this review, we identify three critical areas of research and development needed to advance our understanding of NP production by biofilms: 1) synthesis, 2) mechanism and 3) stabilization. Advancement in these areas could result in the biosynthesis of NPs that are suitable for practical applications, especially in drug delivery and biocatalysis. Specifically, the current status of methods and mechanisms of nanoparticle synthesis and surface stabilization using planktonic bacteria and biofilms is discussed. We conclude that the use of biofilms to synthesize and stabilize NPs is underappreciated and could provide a new direction in biofilm-based NP production. Copyright © 2016 Elsevier Inc. All rights reserved.

Silver, gold, and alloyed silver-gold nanoparticles: characterization and comparative cell-biologic action

NASA Astrophysics Data System (ADS)

Mahl, Dirk; Diendorf, Jörg; Ristig, Simon; Greulich, Christina; Li, Zi-An; Farle, Michael; Köller, Manfred; Epple, Matthias

2012-10-01

Silver, gold, and silver-gold-alloy nanoparticles were prepared by citrate reduction modified by the addition of tannin during the synthesis, leading to a reduction in particle size by a factor of three. Nanoparticles can be prepared by this easy water-based synthesis and subsequently functionalized by the addition of either tris(3-sulfonatophenyl)phosphine or poly( N-vinylpyrrolidone). The resulting nanoparticles of silver (diameter 15-25 nm), gold (5-6 nm), and silver-gold (50:50; 10-12 nm) were easily dispersable in water and also in cell culture media (RPMI + 10 % fetal calf serum), as shown by nanoparticle tracking analysis and differential centrifugal sedimentation. High-resolution transmission electron microscopy showed a polycrystalline nature of all nanoparticles. EDX on single silver-gold nanoparticles indicated that the concentration of gold is higher inside a nanoparticle. The biologic action of the nanoparticles toward human mesenchymal stem cells (hMSC) was different: Silver nanoparticles showed a significant concentration-dependent influence on the viability of hMSC. Gold nanoparticles showed only a small effect on the viability of hMSC after 7 days. Surprisingly, silver-gold nanoparticles had no significant influence on the viability of hMSC despite the silver content. Silver nanoparticles and silver-gold nanoparticles in the concentration range of 5-20 μg mL-1 induced the activation of hMSC as indicated by the release of IL-8. In contrast, gold nanoparticles led to a reduction of the release of IL-6 and IL-8.

The biomolecular corona of nanoparticles in circulating biological media

NASA Astrophysics Data System (ADS)

Pozzi, D.; Caracciolo, G.; Digiacomo, L.; Colapicchioni, V.; Palchetti, S.; Capriotti, A. L.; Cavaliere, C.; Zenezini Chiozzi, R.; Puglisi, A.; Laganà, A.

2015-08-01

When nanoparticles come into contact with biological media, they are covered by a biomolecular `corona', which confers a new identity to the particles. In all the studies reported so far nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let multicomponent liposomes interact with fetal bovine serum (FBS) both statically and dynamically, i.e. in contact with circulating FBS (~40 cm s-1). The structure and composition of the liposome-protein corona, as determined by dynamic light scattering, electrophoretic light scattering and liquid chromatography tandem mass spectrometry, were found to be dependent on the incubation protocol. Specifically, following dynamic exposure to FBS, multicomponent liposomes were less enriched in complement proteins and appreciably more enriched in apolipoproteins and acute phase proteins (e.g. alpha-1-antitrypsin and inter-alpha-trypsin inhibitor heavy chain H3) that are involved in relevant interactions between nanoparticles and living systems. Supported by our results, we speculate that efficient predictive modeling of nanoparticle behavior in vivo will require accurate knowledge of nanoparticle-specific protein fingerprints in circulating biological media.When nanoparticles come into contact with biological media, they are covered by a biomolecular `corona', which confers a new identity to the particles. In all the studies reported so far nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let

Effect of capping agents: Structural, optical and biological properties of ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Javed, Rabia; Usman, Muhammad; Tabassum, Saira; Zia, Muhammad

2016-11-01

Different biological activities of capped and uncapped ZnO nanoparticles were investigated, and the effects of potential capping agents on these biological activities were studied. ZnO nanoparticles were synthesized and capped by polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) using a simple chemical method of co-precipitation. Characterization by X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and UV-vis spectroscopy confirmed the crystallinity, size, functional group, and band gap of synthesized nanoparticles. Reduction in size occurred from 34 nm to 26 nm due to surfactant. Results of all biological activities indicated significantly higher values in capped as compared to uncapped nanoparticles. Antibacterial activity against Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC15224), and Acetobacter was obtained. This activity was more prominent against Gram-positive bacteria, and ZnO-PVP nanoparticles elucidated highest antibacterial activity (zone of inhibition 17 mm) against Gram-positive, Bacillus subtilis species. Antioxidant activities including total flavonoid content, total phenolic content, total antioxidant capacity, total reducing power and %age inhibition of DPPH, and antidiabetic activity against α-amylase enzyme found to be exhibited highest by ZnO-PEG nanoparticles.

Synthesis and standardization of biologically synthesized silver nanoparticles

NASA Astrophysics Data System (ADS)

Roy, Swarup; Das, Tapan Kumar

2013-06-01

The biological silver nanoparticle was synthesized extracellularly by using a fungi Aspergillus foetidus. The live cell filtrate of fungi has been used as reducing agent in the process of nanoparticles synthesis. In 50 ml cell filtrate a volume of AgNO3 stock solution was added to make finally the concentration as 1 mM of AgNO3 and allowed to shake in an incubator for several hrs in dark. The changed color was considered as the primary indication of nanoparticles formation and studies of UV-VIS, DLS, FTIR, AFM, TEM, EDS, Zeta pot. and nitrate reductase assay confirmed the same. It was indicated that stable & 20-40 nm roughly spherical shaped silver nanoparticles was formed. To standardize the nanoparticles biosynthesis different physical parameters like Substrate cone. (0-8 mM), PH-(5-12), Temp.-(5-50°C), incubation time (0-120) hrs and salinity (0.1-1.0 %) were investigated and it was observed that 4 mM AgNO3 conc., PH-9, Temp. -30°C, incubation time 72h and 0.2 % salinity were found to be optimum for the synthesis & stability of the silver nanoparticles.

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study.

PubMed

Rónavári, Andrea; Kovács, Dávid; Igaz, Nóra; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Pfeiffer, Ilona; Kiricsi, Mónika

2017-01-01

Due to obvious disadvantages of the classical chemical methods, green synthesis of metallic nanoparticles has attracted tremendous attention in recent years. Numerous environmentally benign synthesis methods have been developed yielding nanoparticles via low-cost, eco-friendly, and simple approaches. In this study, our aim was to determine the suitability of coffee and green tea extracts in green synthesis of silver nanoparticles as well as to compare the performance of the obtained materials in different biological systems. We successfully produced silver nanoparticles (C-AgNP and GT-AgNP) using coffee and green tea extracts; moreover, based on our comprehensive screening, we delineated major differences in the biological activity of C-AgNPs and GT-AgNPs. Our results indicate that although GT-AgNPs exhibited excellent antimicrobial activity against all the examined microbial pathogens, these particles were also highly toxic to mammalian cells, which limits their potential applications. On the contrary, C-AgNPs manifested substantial inhibitory action on the tested microbes but were nontoxic to human and mouse cells, indicating an outstanding capacity to discriminate between potential pathogens and mammalian cells. These results clearly show that the various green materials used for stabilization and for reduction of metal ions have a defining role in determining and fine-tuning the biological activity of the obtained nanoparticles.

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study

PubMed Central

Rónavári, Andrea; Kovács, Dávid; Igaz, Nóra; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Pfeiffer, Ilona; Kiricsi, Mónika

2017-01-01

Due to obvious disadvantages of the classical chemical methods, green synthesis of metallic nanoparticles has attracted tremendous attention in recent years. Numerous environmentally benign synthesis methods have been developed yielding nanoparticles via low-cost, eco-friendly, and simple approaches. In this study, our aim was to determine the suitability of coffee and green tea extracts in green synthesis of silver nanoparticles as well as to compare the performance of the obtained materials in different biological systems. We successfully produced silver nanoparticles (C-AgNP and GT-AgNP) using coffee and green tea extracts; moreover, based on our comprehensive screening, we delineated major differences in the biological activity of C-AgNPs and GT-AgNPs. Our results indicate that although GT-AgNPs exhibited excellent antimicrobial activity against all the examined microbial pathogens, these particles were also highly toxic to mammalian cells, which limits their potential applications. On the contrary, C-AgNPs manifested substantial inhibitory action on the tested microbes but were nontoxic to human and mouse cells, indicating an outstanding capacity to discriminate between potential pathogens and mammalian cells. These results clearly show that the various green materials used for stabilization and for reduction of metal ions have a defining role in determining and fine-tuning the biological activity of the obtained nanoparticles. PMID:28184158

Spray-Dried Nanoparticle-in-Microparticle Delivery Systems (NiMDS) for Gene Delivery, Comprising Polyethylenimine (PEI)-Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix.

PubMed

Schulze, Jan; Kuhn, Stephanie; Hendrikx, Stephan; Schulz-Siegmund, Michaela; Polte, Tobias; Aigner, Achim

2018-03-01

Nucleic acid-based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid-based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready-to-use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine-based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray-dried nanoparticle-in-microparticle delivery system is presented for the encapsulation of polyethylenimine-based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy-to-handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine-based nanoparticles from the nanoparticle-in-microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle-in-microparticle delivery system is demonstrated as ready-to-use dry powder to be an efficient device for the inhalative delivery of polyethylenimine-based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An investigation of in vivo wound healing activity of biologically synthesized silver nanoparticles

NASA Astrophysics Data System (ADS)

Kaler, Abhishek; Mittal, Amit Kumar; Katariya, Mahesh; Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog; Banerjee, Uttam Chand

2014-09-01

Therapeutic use of nano-silver is claimed to have reduced side effects and enhanced curative activity as compared to its ionic counterpart (silver ions). The present work aims to screen microbes for the synthesis of silver nanoparticles (AgNPs), to formulate the nano-silver-based Carbopol gel and evaluating its wound healing efficacy on rat model. The goal was to develop the topical formulation based on bio-nano-silver to control the infection and healing the wounds with higher efficacy. Procedure involved the use of Saccharomyces boulardii for the synthesis of silver nanoparticles in the size range of 3-10 nm and these nanoparticles were used for the preparation of Carbopol-based nano-silver gel. Highly stable Carbopol nanogel was developed with good rheological properties. The burn wound healing potential of this nano-silver gel was evaluated on SD rats via visual observation, transepidermal water loss and histology of skin. Excellent wound healing was observed with AgNPs. Biologically synthesized AgNPs-based nano-silver gel showed superior wound healing efficacy as compared to marketed formulations and silver ions.

Biological iron-sulfur storage in a thioferrate-protein nanoparticle

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

Vaccaro, Brian J.; Clarkson, Sonya M.; Holden, James F.

Iron–sulfur clusters are ubiquitous in biology and function in electron transfer and catalysis. We assembled them from iron and cysteine sulfur on protein scaffolds. Iron is typically stored as iron oxyhydroxide, ferrihydrite, encapsulated in 12 nm shells of ferritin, which buffers cellular iron availability. We have characterized IssA, a protein that stores iron and sulfur as thioferrate, an inorganic anionic polymer previously unknown in biology. IssA forms nanoparticles reaching 300 nm in diameter and is the largest natural metalloprotein complex known. It is a member of a widely distributed protein family that includes nitrogenase maturation factors, NifB and NifX. IssAmore » nanoparticles are visible by electron microscopy as electron-dense bodies in the cytoplasm. Purified nanoparticles appear to be generated from 20 nm units containing B 6,400 Fe atoms and B 170 IssA monomers. In support of roles in both iron–sulfur storage and cluster biosynthesis, IssA reconstitutes the [4Fe-4S] cluster in ferredoxin in vitro.« less

Biological iron-sulfur storage in a thioferrate-protein nanoparticle

DOE PAGES

Vaccaro, Brian J.; Clarkson, Sonya M.; Holden, James F.; ...

2017-07-20

Iron–sulfur clusters are ubiquitous in biology and function in electron transfer and catalysis. We assembled them from iron and cysteine sulfur on protein scaffolds. Iron is typically stored as iron oxyhydroxide, ferrihydrite, encapsulated in 12 nm shells of ferritin, which buffers cellular iron availability. We have characterized IssA, a protein that stores iron and sulfur as thioferrate, an inorganic anionic polymer previously unknown in biology. IssA forms nanoparticles reaching 300 nm in diameter and is the largest natural metalloprotein complex known. It is a member of a widely distributed protein family that includes nitrogenase maturation factors, NifB and NifX. IssAmore » nanoparticles are visible by electron microscopy as electron-dense bodies in the cytoplasm. Purified nanoparticles appear to be generated from 20 nm units containing B 6,400 Fe atoms and B 170 IssA monomers. In support of roles in both iron–sulfur storage and cluster biosynthesis, IssA reconstitutes the [4Fe-4S] cluster in ferredoxin in vitro.« less

Systematic Computation of Nonlinear Cellular and Molecular Dynamics with Low-Power CytoMimetic Circuits: A Simulation Study

PubMed Central

Papadimitriou, Konstantinos I.; Stan, Guy-Bart V.; Drakakis, Emmanuel M.

2013-01-01

This paper presents a novel method for the systematic implementation of low-power microelectronic circuits aimed at computing nonlinear cellular and molecular dynamics. The method proposed is based on the Nonlinear Bernoulli Cell Formalism (NBCF), an advanced mathematical framework stemming from the Bernoulli Cell Formalism (BCF) originally exploited for the modular synthesis and analysis of linear, time-invariant, high dynamic range, logarithmic filters. Our approach identifies and exploits the striking similarities existing between the NBCF and coupled nonlinear ordinary differential equations (ODEs) typically appearing in models of naturally encountered biochemical systems. The resulting continuous-time, continuous-value, low-power CytoMimetic electronic circuits succeed in simulating fast and with good accuracy cellular and molecular dynamics. The application of the method is illustrated by synthesising for the first time microelectronic CytoMimetic topologies which simulate successfully: 1) a nonlinear intracellular calcium oscillations model for several Hill coefficient values and 2) a gene-protein regulatory system model. The dynamic behaviours generated by the proposed CytoMimetic circuits are compared and found to be in very good agreement with their biological counterparts. The circuits exploit the exponential law codifying the low-power subthreshold operation regime and have been simulated with realistic parameters from a commercially available CMOS process. They occupy an area of a fraction of a square-millimetre, while consuming between 1 and 12 microwatts of power. Simulations of fabrication-related variability results are also presented. PMID:23393550

Nuclear Receptors and AMPK: Can Exercise Mimetics Cure Diabetes?

PubMed Central

Wall, Christopher E.; Yu, Ruth T.; Atkins, Anne R.; Downes, Michael; Evans, Ronald M.

2016-01-01

Endurance exercise can lead to systemic improvements in insulin sensitivity and metabolic homeostasis, and is an effective approach to combat metabolic diseases. Pharmacological compounds that recapitulate the beneficial effects of exercise, also known as “exercise mimetics,” have the potential to improve disease symptoms of metabolic syndrome. These drugs, which can increase energy expenditure, suppress hepatic gluconeogenesis, and induce insulin sensitization, have accordingly been highly scrutinized for their utility in treating metabolic diseases including diabetes. Nevertheless, the identity of an efficacious exercise mimetic still remains elusive. In this article, we will highlight several nuclear receptors and cofactors that are putative molecular targets for exercise mimetics, and review recent studies that provide advancements in our mechanistic understanding of how exercise mimetics exert their beneficial effects. We will also discuss evidence from clinical trials utilizing these compounds in human subjects to evaluate their efficacy in treating diabetes. PMID:27106806

Effective biological dose from occupational exposure during nanoparticle synthesis

NASA Astrophysics Data System (ADS)

Demou, Evangelia; Tran, Lang; Housiadas, Christos

2009-02-01

Nanomaterial and nanotechnology safety require the characterization of occupational exposure levels for completing a risk assessment. However, equally important is the estimation of the effective internal dose via lung deposition, transport and clearance mechanisms. An integrated source-to-biological dose assessment study is presented using real monitoring data collected during nanoparticle synthesis. Experimental monitoring data of airborne exposure levels during nanoparticle synthesis of CaSO4 and BiPO4 nanoparticles in a research laboratory is coupled with a human lung transport and deposition model, which solves in an Eulerian framework the general dynamic equation for polydisperse aerosols using particle specific physical-chemical properties. Subsequently, the lung deposition model is coupled with a mathematical particle clearance model providing the effective biological dose as well as the time course of the biological dose build-up after exposure. The results for the example of BiPO4 demonstrate that even short exposures throughout the day can lead to particle doses of 1.10·E+08#/(kg-bw·8h-shift), with the majority accumulating in the pulmonary region. Clearance of particles is slow and is not completed within a working shift following a 1 hour exposure. It mostly occurs via macrophage activity in the alveolar region, with small amounts transported to the interstitium and less to the lymph nodes.

From the iron boring scraps to superparamagnetic nanoparticles through an aerobic biological route.

PubMed

Daneshvar, Majid; Hosseini, Mohammad Raouf

2018-06-15

A straightforward, highly efficient, and low-cost biological route was introduced for the synthesis of magnetic nanoparticles. Three urease-positive bacteria namely, Bacillus subtilis, B. pasteurii, and B. licheniformis were used to biosynthesize ammonia and biosurfactants required for the nanoparticle production. Also, the features of the applied biological approach was compared with a chemical co-precipitation method. X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating-sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR) were applied to characterize the synthesized nanoparticles. Results indicated that the biologically fabricated powders had a single domain structure, and their mean particle size was in the range of 37 to 97 nm. The production capacity of the biological processes was double the chemical method, and the biosynthesized superparamagnetic nanoparticles had higher saturation magnetization up to 132 emu/g. Finally, the removal of Cr(VI) from a synthetic solution was investigated using the four products. The maximum elimination of chromium (over 99%) was achieved by the particles synthesized by B. pasteurii, with the adsorption capacity of 190 mg/g. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantitative characterization of nanoparticle agglomeration within biological media

NASA Astrophysics Data System (ADS)

Hondow, Nicole; Brydson, Rik; Wang, Peiyi; Holton, Mark D.; Brown, M. Rowan; Rees, Paul; Summers, Huw D.; Brown, Andy

2012-07-01

Quantitative analysis of nanoparticle dispersion state within biological media is essential to understanding cellular uptake and the roles of diffusion, sedimentation, and endocytosis in determining nanoparticle dose. The dispersion of polymer-coated CdTe/ZnS quantum dots in water and cell growth medium with and without fetal bovine serum was analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Characterization by TEM of samples prepared by plunge freezing the blotted solutions into liquid ethane was sensitive to the dispersion state of the quantum dots and enabled measurement of agglomerate size distributions even in the presence of serum proteins where DLS failed. In addition, TEM showed a reduced packing fraction of quantum dots per agglomerate when dispersed in biological media and serum compared to just water, highlighting the effect of interactions between the media, serum proteins, and the quantum dots. The identification of a heterogeneous distribution of quantum dots and quantum dot agglomerates in cell growth medium and serum by TEM will enable correlation with the previously reported optical metrology of in vitro cellular uptake of this quantum dot dispersion. In this paper, we present a comparative study of TEM and DLS and show that plunge-freeze TEM provides a robust assessment of nanoparticle agglomeration state.

Study of magnetic nanoparticles and overcoatings for biological applications including a sensor device

NASA Astrophysics Data System (ADS)

Grancharov, Stephanie G.

I. A general introduction to the field of nanomaterials is presented, highlighting their special attributes and characteristics. Nanoparticles in general are discussed with respect to their structure, form and properties. Magnetic particles in particular are highlighted, especially the iron oxides. The importance and interest of integrating these materials with biological media is discussed, with emphasis on transferring particles from one medium to another, and subsequent modification of surfaces with different types of materials. II. A general route to making magnetic iron oxide nanoparticles is explained, both as maghemite and magnetite, including properties of the particles and characterization. A novel method of producing magnetite particles without a ligand is then presented, with subsequent characterization and properties described. III. Attempts to coat iron oxide nanoparticles with a view to creating biofunctional magnetic nanoparticles are presented, using a gold overcoating method. Methods of synthesis and characterization are examined, with unique problems to core-shell structures analyzed. IV. Solubility of nanoparticles in both aqueous and organic media is discussed and examined. The subsequent functionalization of the surface of maghemite and magnetite nanoparticles with a variety of biomaterials including block copolypeptides, phospholipids and carboxydextran is then presented. These methods are integral to the use of magnetic nanoparticles in biological applications, and therefore their properties are examined once tailored with these molecules. V. A new type of magnetic nanoparticle sensor-type device is described. This device integrates bio-and DNA-functionalized nanoparticles with conjugate functionalized silicon dioxide surfaces. These techniques to pattern particles to a surface are then incorporated into a device with a magnetic tunnel junction, which measures magnetoresistance in the presence of an external magnetic field. This configuration

The Co-Occurrence of Quotatives with Mimetic Performances.

ERIC Educational Resources Information Center

Buchstaller, Isabelle

2003-01-01

This paper discusses mimesis, the direct representation and total imitation of an event. It studies the co-occurrence of quotative verbs with mimetic enactment based on two corpora of U.S. American English, both available through the University of Pennsylvania Data Consortium. The Switchboard Corpus has 542 speakers ranging in age from 20-60 years…

Haemocompatibility assessment of synthesised platinum nanoparticles and its implication in biology.

PubMed

Shiny, P J; Mukherjee, Amitava; Chandrasekaran, N

2014-06-01

The growing need for advanced treatment of evolving diseases has become a motivation for this study. Among the noble metals, platinum nanoparticles are of importance because of their catalytic property, antioxidant potential, minimal toxicity and diverse applications. Biological process of synthesis has retained its significance, because it is a simple one-step process yielding stable nanoparticles. Herein, we have synthesised platinum nanoparticles through a green process using the unexplored seaweed Padina gymnospora, a brown alga. The course of synthesis was monitored and the nanoparticles were characterised using UV-visible spectroscopy. The synthesised nanoparticles were studied using TEM, XRD and FTIR. The TEM and XRD studies reveal the size of the nanoparticle to be <35 nm. The catalytic nanoparticles were capable of oxidising NADH to NAD(+). The biocompatibility was tested by haemolytic assay for the furtherance of the application of platinum nanoparticles in medicine. This is the first report on the biogenic synthesis of platinum nanoparticles using seaweed.

EPOR-Based Purification and Analysis of Erythropoietin Mimetic Peptides from Human Urine by Cys-Specific Cleavage and LC/MS/MS

NASA Astrophysics Data System (ADS)

Vogel, Matthias; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

2015-09-01

The development of a new class of erythropoietin mimetic agents (EMA) for treating anemic conditions has been initiated with the discovery of oligopeptides capable of dimerizing the erythropoietin (EPO) receptor and thus stimulating erythropoiesis. The most promising amino acid sequences have been mounted on various different polymeric structures or carrier molecules to obtain highly active EPO-like drugs exhibiting beneficial and desirable pharmacokinetic profiles. Concomitant with creating new therapeutic options, erythropoietin mimetic peptide (EMP)-based drug candidates represent means to artificially enhance endurance performance and necessitate coverage by sports drug testing methods. Therefore, the aim of the present study was to develop a strategy for the comprehensive detection of EMPs in doping controls, which can be used complementary to existing protocols. Three model EMPs were used to provide proof-of-concept data. Following EPO receptor-facilitated purification of target analytes from human urine, the common presence of the cysteine-flanked core structure of EMPs was exploited to generate diagnostic peptides with the aid of a nonenzymatic cleavage procedure. Sensitive detection was accomplished by targeted-SIM/data-dependent MS2 analysis. Method characterization was conducted for the EMP-based drug peginesatide concerning specificity, linearity, precision, recovery, stability, ion suppression/enhancement, and limit of detection (LOD, 0.25 ng/mL). Additionally, first data for the identification of the erythropoietin mimetic peptides EMP1 and BB68 were generated, demonstrating the multi-analyte testing capability of the presented approach.

Calorimetric studies of the interactions of metalloenzyme active site mimetics with zinc-binding inhibitors.

PubMed

Robinson, Sophia G; Burns, Philip T; Miceli, Amanda M; Grice, Kyle A; Karver, Caitlin E; Jin, Lihua

2016-07-19

The binding of drugs to metalloenzymes is an intricate process that involves several interactions, including binding of the drug to the enzyme active site metal, as well as multiple interactions between the drug and the enzyme residues. In order to determine the free energy contribution of Zn(2+) binding by known metalloenzyme inhibitors without the other interactions, valid active site zinc structural mimetics must be formed and binding studies need to be performed in biologically relevant conditions. The potential of each of five ligands to form a structural mimetic with Zn(2+) was investigated in buffer using Isothermal Titration Calorimetry (ITC). All five ligands formed strong 1 : 1 (ligand : Zn(2+)) binary complexes. The complexes were used in further ITC experiments to study their interaction with 8-hydroxyquinoline (8-HQ) and/or acetohydroxamic acid (AHA), two bidentate anionic zinc-chelating enzyme inhibitors. It was found that tetradentate ligands were not suitable for creating zinc structural mimetics for inhibitor binding in solution due to insufficient coordination sites remaining on Zn(2+). A stable binary complex, [Zn(BPA)](2+), which was formed by a tridentate ligand, bis(2-pyridylmethyl)amine (BPA), was found to bind one AHA in buffer or a methanol : buffer mixture (60 : 40 by volume) at pH 7.25 or one 8-HQ in the methanol : buffer mixture at pH 6.80, making it an effective structural mimetic for the active site of zinc metalloenzymes. These results are consistent with the observation that metalloenzyme active site zinc ions have three residues coordinated to them, leaving one or two sites open for inhibitors to bind. Our findings indicate that Zn(BPA)X2 can be used as an active site structural mimetic for zinc metalloenzymes for estimating the free energy contribution of zinc binding to the overall inhibitor active site interactions. Such use will help aid in the rational design of inhibitors to a variety of zinc metalloenzymes.

Probing nanoparticles and nanoparticle-conjugated biomolecules using time-of-flight secondary ion mass spectrometry.

PubMed

Kim, Young-Pil; Shon, Hyun Kyong; Shin, Seung Koo; Lee, Tae Geol

2015-01-01

Bio-conjugated nanoparticles have emerged as novel molecular probes in nano-biotechnology and nanomedicine and chemical analyses of their surfaces have become challenges. The time-of-flight (TOF) secondary ion mass spectrometry (SIMS) has been one of the most powerful surface characterization techniques for both nanoparticles and biomolecules. When combined with various nanoparticle-based signal enhancing strategies, TOF-SIMS can probe the functionalization of nanoparticles as well as their locations and interactions in biological systems. Especially, nanoparticle-based SIMS is an attractive approach for label-free drug screening because signal-enhancing nanoparticles can be designed to directly measure the enzyme activity. The chemical-specific imaging analysis using SIMS is also well suited to screen nanoparticles and nanoparticle-biomolecule conjugates in complex environments. This review presents some recent applications of nanoparticle-based TOF-SIMS to the chemical analysis of complex biological systems. © 2014 Wiley Periodicals, Inc.

A Novel Peptide Thrombopoietin Mimetic Designing and Optimization Using Computational Approach

PubMed Central

Singh, Vimal Kishor; Kumar, Neeraj; Kalsan, Manisha; Saini, Abhishek; Chandra, Ramesh

2016-01-01

Thrombopoietin receptor (TPOR) is a cytokine receptor protein present on the cell surface. The activation of TPOR by thrombopoietin (TPO) (a glycoprotein hormone) triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. Recent studies on ex vivo megakaryocytopoiesis have evolved the possibilities of therapeutics uses. These findings have paved the way for the development of various TPO alternatives (recombinant TPO, peptide, and non-peptide TPO mimetics), which are useful in regenerative medicine. However, these alternatives possess various limitations such as induction of autoimmune effects, high production cost, low specificity, and hence activity. In the present study, a novel peptidic TPO mimetic was designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro. These studies indicated mimetic-9 as a significant molecule since it was found to have better binding score of −938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of −798.4 kcal/mol and TMP dimer with docking score of −811.9 kcal/mol for TPOR. Mimetic9-TPOR complex was further assessed by the molecular dynamics simulation, and their complex was found to be stable with an RMSD value of 0.091 Å. While studying the parameters, mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY) score and high instability index score and was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO for in vitro platelet production with higher efficiency. PMID:27630985

A Novel Peptide Thrombopoietin Mimetic Designing and Optimization Using Computational Approach.

PubMed

Singh, Vimal Kishor; Kumar, Neeraj; Kalsan, Manisha; Saini, Abhishek; Chandra, Ramesh

2016-01-01

Thrombopoietin receptor (TPOR) is a cytokine receptor protein present on the cell surface. The activation of TPOR by thrombopoietin (TPO) (a glycoprotein hormone) triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. Recent studies on ex vivo megakaryocytopoiesis have evolved the possibilities of therapeutics uses. These findings have paved the way for the development of various TPO alternatives (recombinant TPO, peptide, and non-peptide TPO mimetics), which are useful in regenerative medicine. However, these alternatives possess various limitations such as induction of autoimmune effects, high production cost, low specificity, and hence activity. In the present study, a novel peptidic TPO mimetic was designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro. These studies indicated mimetic-9 as a significant molecule since it was found to have better binding score of -938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of -798.4 kcal/mol and TMP dimer with docking score of -811.9 kcal/mol for TPOR. Mimetic9-TPOR complex was further assessed by the molecular dynamics simulation, and their complex was found to be stable with an RMSD value of 0.091 Å. While studying the parameters, mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY) score and high instability index score and was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO for in vitro platelet production with higher efficiency.

Acellular assessments of engineered-manufactured nanoparticle biological surface reactivity

EPA Science Inventory

It is critical to assess the surface properties and reactivity of engineered-manufactured nanoparticles (NPs) as these will influence their interactions with biological systems, biokinetics and toxicity. We examined the physicochemical properties and surface reactivity of metal o...

Silica passivated conjugated polymer nanoparticles for biological imaging applications

NASA Astrophysics Data System (ADS)

Bourke, Struan; Urbano, Laura; Olona, Antoni; Valderrama, Ferran; Dailey, Lea Ann; Green, Mark A.

2017-02-01

Colorectal and prostate cancers are major causes of cancer-related death, with early detection key to increased survival. However, as symptoms occur during advanced stages and current diagnostic methods have limitations, there is a need for new fluorescent probes that remain bright, are biocompatible and can be targeted. Conjugated polymer nanoparticles have shown great promise in biological imaging due to their unique optical properties. We have synthesised small, bright, photo-stable CN-PPV, nanoparticles encapsulated with poloxamer polymer and a thin silica shell. By incubating the CN-PPV silica shelled cross-linked (SSCL) nanoparticles in mammalian (HeLa) cells; we were able to show that cellular uptake occurred. Uptake was also shown by incubating the nanoparticles in RWPE-1, WPE1-NB26 and WPE1- NA22 prostate cancer cell lines. Finally, HEK cells were used to show the particles had limited cytotoxicity.

On (in)stabilities of perturbations in mimetic models with higher derivatives

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

Zheng, Yunlong; Shen, Liuyuan; Mou, Yicen

2017-08-01

Usually when applying the mimetic model to the early universe, higher derivative terms are needed to promote the mimetic field to be dynamical. However such models suffer from the ghost and/or the gradient instabilities and simple extensions cannot cure this pathology. We point out in this paper that it is possible to overcome this difficulty by considering the direct couplings of the higher derivatives of the mimetic field to the curvature of the spacetime.

NEC violation in mimetic cosmology revisited

DOE PAGES

Ijjas, Anna; Ripley, Justin; Steinhardt, Paul J.

2016-06-28

In the context of Einstein gravity, if the null energy condition (NEC) is satisfied, the energy density in expanding space–times always decreases while in contracting space–times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show thatmore » mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples). Most interestingly, the source of the instability is always the Einstein–Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. Finally, we also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.« less

NEC violation in mimetic cosmology revisited

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

Ijjas, Anna; Ripley, Justin; Steinhardt, Paul J.

In the context of Einstein gravity, if the null energy condition (NEC) is satisfied, the energy density in expanding space–times always decreases while in contracting space–times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show thatmore » mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples). Most interestingly, the source of the instability is always the Einstein–Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. Finally, we also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.« less

Promotion of hair growth by newly synthesized ceramide mimetic compound.

PubMed

Park, Bu-Mahn; Bak, Soon-Sun; Shin, Kyung-Oh; Kim, Minhee; Kim, Daehwan; Jung, Sang-Hun; Jeong, Sekyoo; Sung, Young Kwan; Kim, Hyun Jung

2017-09-09

Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models. BOI treatment promoted hair growth in cultured human hair follicles ex vivo and induced earlier conversion of telogen into anagen. Although we did not find a significant enhancement of growth factor expression and follicular cell proliferation, BOI treatment resulted in an increased sphinganine and sphingosine contents as well as increased ceramides contents in cultured dermal papilla (DP) cells. Taken together, our data strongly suggest that biologically active pseudoceramide promotes hair growth by stimulating do novo synthesis of sphingolipids in DP cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Mimetic compact stars

NASA Astrophysics Data System (ADS)

Momeni, D.; Moraes, P. H. R. S.; Gholizade, H.; Myrzakulov, R.

Modified gravity models have been constantly proposed with the purpose of evading some standard gravity shortcomings. Recently proposed by Chamseddine and Mukhanov, the Mimetic Gravity arises as an optimistic alternative. Our purpose in this work is to derive Tolman-Oppenheimer-Volkoff equations and solutions for such a gravity theory. We solve them numerically for quark star and neutron star cases. The results are carefully discussed.

Superstretchable Nacre-Mimetic Graphene/Poly(vinyl alcohol) Composite Film Based on Interfacial Architectural Engineering.

PubMed

Zhao, Nifang; Yang, Miao; Zhao, Qian; Gao, Weiwei; Xie, Tao; Bai, Hao

2017-05-23

Through designing hierarchical structures, particularly optimizing the chemical and architectural interactions at its inorganic/organic interface, nacre has achieved an excellent combination of contradictory mechanical properties such as strength and toughness, which is highly demanded yet difficult to achieve by most synthetic materials. Most techniques applied to develop nacre-mimetic composites have been focused on mimicking the "brick-and-mortar" structure, but the interfacial architectural features, especially the asperities and mineral bridges of "bricks", have been rarely concerned, which are of equal importance for enhancing mechanical properties of nacre. Here, we used a modified bidirectional freezing method followed by uniaxial pressing and chemical reduction to assemble a nacre-mimetic graphene/poly(vinyl alcohol) composite film, with both asperities and bridges introduced in addition to the lamellar layers to mimic the interfacial architectural interactions found in nacre. As such, we have developed a composite film that is not only strong (up to ∼150.9 MPa), but also tough (up to ∼8.50 MJ/m 3 ), and highly stretchable (up to ∼10.44%), difficult to obtain by other methods. This was all achieved by only interfacial architectural engineering within the traditional "brick-and-mortar" structure, without introducing a third component or employing chemical cross-linker as in some other nacre-mimetic systems. More importantly, we believe that the design principles and processing strategies reported here can also be applied to other material systems to develop strong and stretchable materials.

Dispersal of mimetic seeds of three species of Ormosia (Leguminosae)

USGS Publications Warehouse

Foster, M.S.; DeLay, L.S.

1998-01-01

Seeds with 'imitation arils' appear wholly or partially covered by pulp or aril but actually carry no fleshy material. The mimetic seed hypothesis to explain this phenomenon proposes a parasitic relationship in which birds are deceived into dispersing seeds that resemble bird-dispersed fruits, without receiving a nutrient reward. The hard-seed for grit hypothesis proposes a mutualistic relationship in which large, terrestrial birds swallow the exceptionally hard 'mimetic' seeds as grit for grinding the softer seeds on which they feed. They defecate, dispersing the seeds, and abrade the seed surface, enhancing germination. Any fruit mimicry is incidental. Fruiting trees of Ormosia spp. (Leguminosae: Papilionoideae) were observed to ascertain mechanisms of seed dispersal and the role of seemingly mimetic characteristics of the seeds in that dispersal. Seed predation and seed germination were also examined. Ormosia isthamensis and O. macrocalyx (but not O. bopiensis) deceived arboreally-foraging frugivorous birds into taking their mimetic seeds, although rates of seed dispersal were low. These results are consistent with the mimetic seed hypothesis. On the other hand, the rates of disappearance of seeds from the ground under the Ormosia trees, hardness of the seeds, and enhancement of germination with the abrasion of the seed coat are all consistent with the hard-seed for grit hypothesis.

Use of Complementary Approaches to Imaging Biomolecules and Endogenous and Exogenous Trace Elements and Nanoparticles in Biological Samples

NASA Astrophysics Data System (ADS)

Brown, Koshonna Dinettia

X-ray Fluorescence Microscopy (XFM) is a useful technique for study of biological samples. XFM was used to map and quantify endogenous biological elements as well as exogenous materials in biological samples, such as the distribution of titanium dioxide (TiO2) nanoparticles. TiO 2 nanoparticles are produced for many different purposes, including development of therapeutic and diagnostic particles for cancer detection and treatment, drug delivery, and induction of DNA breaks. Delivery of such nanoparticles can be targeted to specific cells and subcellular structures. In this work, we develop two novel approaches to stain TiO2 nanoparticles for optical microscopy and to confirm that staining by XFM. The first approach utilizes fluorescent biotin and fluorescent streptavidin to label the nanoparticles before and after cellular uptake; the second approach is based on the copper-catalyzed azide-alkyne cycloaddition, the so-called CLICK chemistry, for labeling of azide conjugated TiO2 nanoparticles with "clickable" dyes such as alkyne Alexa Fluor dyes with a high fluorescent yield. To confirm that the optical fluorescence signals of nanoparticles stained in situ match the distribution of the Ti element, we used high resolution synchrotron X-Ray Fluorescence Microscopy (XFM) using the Bionanoprobe instrument at the Advanced Photon Source at Argonne National Laboratory. Titanium-specific X-ray fluorescence showed excellent overlap with the location of Alexa Fluor optical fluorescence detected by confocal microscopy. In this work XFM was also used to investigate native elemental differences between two different types of head and neck cancer, one associated with human papilloma virus infection, the other virus free. Future work may see a cross between these themes, for example, exploration of TiO2 nanoparticles as anticancer treatment for these two different types of head and neck cancer.

Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy

PubMed Central

Miele, Evelina; Spinelli, Gian Paolo; Miele, Ermanno; Di Fabrizio, Enzo; Ferretti, Elisabetta; Tomao, Silverio; Gulino, Alberto

2012-01-01

During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA) is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi). RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current treatment regimens in a substantial way. These nanoparticles could be designed to surmount one or more of the barriers encountered by siRNA. Nanoparticle drug formulations afford the chance to improve drug bioavailability, exploiting superior tissue permeability, payload protection, and the “stealth” features of these entities. The main aims of this review are: to explain the siRNA mechanism with regard to potential applications in siRNA-based cancer therapy; to discuss the possible usefulness of nanoparticle-based delivery of certain molecules for overcoming present therapeutic limitations; to review the ongoing relevant clinical research with its pitfalls and

Biomarkers of Nanoparticles Impact on Biological Systems

NASA Astrophysics Data System (ADS)

Mikhailenko, V.; Ieleiko, L.; Glavin, A.; Sorochinska, J.

Studies of nanoscale mineral fibers have demonstrated that the toxic and carcinogenic effects are related to the surface area and surface activity of inhaled particles. Particle surface characteristics are considered to be key factors in the generation of free radicals and reactive oxygen species and are related to the development of apoptosis or cancer. Existing physico-chemical methods do not always allow estimation of the nanoparticles impact on organismal and cellular levels. The aim of this study was to develop marker system for evaluation the toxic and carcinogenic effects of nanoparticles on cells. The markers are designed with respect to important nanoparticles characteristics for specific and sensitive assessment of their impact on biological system. We have studied DNA damage, the activity of xanthine oxidoreductase influencing the level of free radicals, bioenergetic status, phospholipids profile and formation of 1H-NMR-visible mobile lipid domains in Ehrlich carcinoma cells. The efficiency of the proposed marker system was tested in vivo and in vitro with the use of C60 fullerene nanoparticles and multiwalled carbon nanotubes. Our data suggest that multiwalled carbon nanotubes and fullerene C60 may pose genotoxic effect, change energy metabolism and membrane structure, alter free radical level via xanthine oxidase activation and cause mobile lipid domains formation as determined in vivo and in vitro studies on Ehrlich carcinoma cells.

3-Dimensional quantitative detection of nanoparticle content in biological tissue samples after local cancer treatment

NASA Astrophysics Data System (ADS)

Rahn, Helene; Alexiou, Christoph; Trahms, Lutz; Odenbach, Stefan

2014-06-01

X-ray computed tomography is nowadays used for a wide range of applications in medicine, science and technology. X-ray microcomputed tomography (XμCT) follows the same principles used for conventional medical CT scanners, but improves the spatial resolution to a few micrometers. We present an example of an application of X-ray microtomography, a study of 3-dimensional biodistribution, as along with the quantification of nanoparticle content in tumoral tissue after minimally invasive cancer therapy. One of these minimal invasive cancer treatments is magnetic drug targeting, where the magnetic nanoparticles are used as controllable drug carriers. The quantification is based on a calibration of the XμCT-equipment. The developed calibration procedure of the X-ray-μCT-equipment is based on a phantom system which allows the discrimination between the various gray values of the data set. These phantoms consist of a biological tissue substitute and magnetic nanoparticles. The phantoms have been studied with XμCT and have been examined magnetically. The obtained gray values and nanoparticle concentration lead to a calibration curve. This curve can be applied to tomographic data sets. Accordingly, this calibration enables a voxel-wise assignment of gray values in the digital tomographic data set to nanoparticle content. Thus, the calibration procedure enables a 3-dimensional study of nanoparticle distribution as well as concentration.

Temperature-sensitive elastin-mimetic dendrimers: Effect of peptide length and dendrimer generation to temperature sensitivity.

PubMed

Kojima, Chie; Irie, Kotaro; Tada, Tomoko; Tanaka, Naoki

2014-06-01

Dendrimers are synthetic macromolecules with unique structure, which are a potential scaffold for peptides. Elastin is one of the main components of extracellular matrix and a temperature-sensitive biomacromolecule. Previously, Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers using different length peptides and different dendrimer generations were synthesized to control the temperature dependency. The elastin-mimetic dendrimers formed β-turn structure by heating, which was similar to the elastin-like peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition, largely depending on the peptide length and slightly depending on the dendrimer generation. The elastin-mimetic dendrimers formed aggregates after the phase transition. The endothermal peak was observed in elastin-mimetic dendrimers with long peptides, but not with short ones. The peptide length and the dendrimer generation are important factors to tune the temperature dependency on the elastin-mimetic dendrimer. Copyright © 2013 Wiley Periodicals, Inc.

Conformational assembly and biological properties of collagen mimetic peptides and their thermally responsive polymer conjugates

NASA Astrophysics Data System (ADS)

Krishna, Ohm Divyam

2011-12-01

Collagens are one of the most abundant proteins found in body tissues and organs, endowing structural integrity, mechanical strength, and multiple biological functions. Destabilized collagen inside human body leads to various degenerative diseases (ex. osteoarthritis) and ageing. This has continued to motivate the design of synthetic peptides and bio-synthetic polypeptides to closely mimic the native collagens in terms of triple helix structure and stability, potential for higher order assembly, and biological properties. However, the widespread application of de novo collagens has been limited in part by the need for hydroxylated proline in the formation of stable triple helical structures. To address this continued need, a hydroxyproline-free, thermally stable collagen-mimetic peptide (CLP-Cys) was rationally designed via the incorporation of electrostatically stabilized amino acid triplets. CLP-Cys was synthesized via solid phase peptide synthesis. The formation and stability of the triple helical structure were indicated via circular dichroism (CD) experiments and confirmed via differential scanning calorimetry (DSC) results. CLP-Cys also self-assembled into nano-rods and micro-fibrils, as evidenced via a combination of dynamic light scattering and transmission electron microscopy. Given the high thermal stability and its propensity for higher-order assembly, CLP-Cys was further functionalized at both the ends with a thermally responsive polymer, poly(diethylene glycol methyl ether methacrylate), (PDEGMEMA) to synthesize a biohybrid triblock copolymer. The CD results indicated that the triple helical form is retained, the thermal unfolding is sustained and helix to coil transition is reversible in the triblock hybrid context. The LCST of PDEGMEMA homopolymer (26 °C) is increased (to 35 °C) upon conjugation to the hydrophilic collagen peptide domain. Further, a combination of static light scattering, Cryo-SEM, TEM and confocal microscopy elucidated that the

Vascular cemeteries formed by biological nanoparticles

NASA Astrophysics Data System (ADS)

Sommer, Andrei P.; Tsurumoto, Toshiyuki

2013-04-01

We report the discovery of dense colonies of globular structures ranging from 100 nm to 5 μm in the tunica media of the femoral artery of an 89-year-old female cadaver. Systematic analysis using scanning electron microscopy, energy dispersive X-ray spectroscopy and light microscopy reveals that the globular structures are surrounded by vascular smooth muscle cells (VSMCs) and consist predominantly of calcium phosphate. Inspection of the images suggests the action of two complementary growth processes. The structures may grow both in size and in number locally by Ostwald ripening and a replicative route, respectively. Morphology in conjunction with the quality of their native growth niche suggests that they are different from nanocrystals released from apoptotic bodies. Their tendency to fill VSMC pockets leads to the speculation that they could represent an effort of the VSMC system to wall off cytotoxic nanocrystals liberated from apoptotic bodies. Alternatively, the structures may be equivalent with nanobacteria (NB)—a nomenclature which caused confusion. This is reflected by the multitude of names used by different authors for the nanoentities (living nanovesicles, nanobionta, calcifying nanoparticles, and nanons). Indeed, there is no clear definition in the literature as to what NB are. Considering that the calcium phosphate nanoparticles have been identified in the human body, we used in our study the descriptive name biological nanoparticles—the world's first nanoparticles.

Magnetic core/shell nanoparticle thin films deposited by MAPLE: Investigation by chemical, morphological and in vitro biological assays

NASA Astrophysics Data System (ADS)

Cristescu, R.; Popescu, C.; Socol, G.; Iordache, I.; Mihailescu, I. N.; Mihaiescu, D. E.; Grumezescu, A. M.; Balan, A.; Stamatin, I.; Chifiriuc, C.; Bleotu, C.; Saviuc, C.; Popa, M.; Chrisey, D. B.

2012-09-01

We report on thin film deposition of nanostructured Fe3O4/oleic acid/ceftriaxone and Fe3O4/oleic acid/cefepime nanoparticles (core/shell/adsorption-shell) were fabricated by matrix assisted pulsed laser evaporation (MAPLE) onto inert substrates. The thin films were characterized by profilometry, Fourier transform infrared spectroscopy, atomic force microscopy, and investigated by in vitro biological assays. The biological properties tested included the investigation of the microbial viability and the microbial adherence to the glass coverslip nanoparticle film, using Gram-negative and Gram-positive bacterial strains with known antibiotic susceptibility behavior, the microbial adherence to the HeLa cells monolayer grown on the nanoparticle pellicle, and the cytotoxicity on eukaryotic cells. The proposed system, based on MAPLE, could be used for the development of novel anti-microbial materials or strategies for fighting pathogenic biofilms frequently implicated in the etiology of biofilm associated chronic infections.

Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer

PubMed Central

Chauhan, Arun; Zubair, Swaleha; Tufail, Saba; Sherwani, Asif; Sajid, Mohammad; Raman, Suri C; Azam, Amir; Owais, Mohammad

2011-01-01

Background Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. Methods and results Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20–40 nm and nonspherical gold particles were found to be 60–80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. Conclusion The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells. PMID:22072868

Quantitative Characterization of Magnetic Mobility of Nanoparticle in Solution-Based Condition.

PubMed

Rodoplu, Didem; Boyaci, Ismail H; Bozkurt, Akif G; Eksi, Haslet; Zengin, Adem; Tamer, Ugur; Aydogan, Nihal; Ozcan, Sadan; Tugcu-Demiröz, Fatmanur

2015-01-01

Magnetic nanoparticles are considered as the ideal substrate to selectively isolate target molecules or organisms from sample solutions in a wide variety of applications including bioassays, bioimaging and environmental chemistry. The broad array of these applications in fields requires the accurate magnetic characterization of nanoparticles for a variety of solution based-conditions. Because the freshly synthesized magnetic nanoparticles demonstrated a perfect magnetization value in solid form, they exhibited a different magnetic behavior in solution. Here, we present simple quantitative method for the measurement of magnetic mobility of nanoparticles in solution-based condition. Magnetic mobility of the nanoparticles was quantified with initial mobility of the particles using UV-vis absorbance spectroscopy in water, ethanol and MES buffer. We demonstrated the efficacy of this method through a systematic characterization of four different core-shell structures magnetic nanoparticles over three different surface modifications. The solid nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and saturation magnetization (Ms). The surfaces of the nanoparticles were functionalized with 11-mercaptoundecanoic acid and bovine serum albumin BSA was selected as biomaterial. The effect of the surface modification and solution media on the stability of the nanoparticles was monitored by zeta potentials and hydrodynamic diameters of the nanoparticles. Results obtained from the mobility experiments indicate that the initial mobility was altered with solution media, surface functionalization, size and shape of the magnetic nanoparticle. The proposed method easily determines the interactions between the magnetic nanoparticles and their surrounding biological media, the magnetophoretic responsiveness of nanoparticles and the initial mobilities of the nanoparticles.

Magnetic nanoparticles in different biological environments analyzed by magnetic particle spectroscopy

NASA Astrophysics Data System (ADS)

Löwa, Norbert; Seidel, Maria; Radon, Patricia; Wiekhorst, Frank

2017-04-01

Quantification of magnetic iron oxide nanoparticles (MNP) in biological systems like cells, tissue, or organs is of vital importance for development of novel biomedical applications, e.g. magnetofection, drug targeting or hyperthermia. Among others, the recently developed magnetic measurement technique magnetic particle spectroscopy (MPS) provides signals that are specific for MNP. MPS is based on the non-linear magnetic response of MNP exposed to a strong sinusoidal excitation field of up to 25 mT amplitude and 25 kHz frequency. So far, it has been proven a powerful tool for quantification of MNP in biological systems. In this study we investigated in detail the influence of typical biological media on the magnetic behavior of different MNP systems by MPS. The results reveal that amplitude and shape (ratio of harmonics) of the MPS spectra allow for perceptively monitoring changes in MNP magnetism caused by different physiological media. Additionally, the observed linear correlation between MPS amplitude and shape alterations can be used to reduce the quantification uncertainty for MNP suspended in a biological environment.

Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides.

PubMed

Tan, Roger S; Naruchi, Kentaro; Amano, Maho; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2015-09-18

A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems.

Actinobacteria mediated synthesis of nanoparticles and their biological properties: A review.

PubMed

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2016-01-01

Nanotechnology is gaining tremendous attention in the present century due to its expected impact on many important areas such as medicine, energy, electronics, and space industries. In this context, actinobacterial biosynthesis of nanoparticles is a reliable, eco-friendly, and important aspect of green chemistry approach that interconnects microbial biotechnology and nanobiotechnology. Antibiotics produced by actinobacteria are popular in almost all the therapeutic measures and it is known that these microbes are also helpful in the biosynthesis of nanoparticles with good surface and size characteristics. In fact, actinobacteria are efficient producers of nanoparticles that show a range of biological properties, namely, antibacterial, antifungal, anticancer, anti-biofouling, anti-malarial, anti-parasitic, antioxidant, etc. This review describes the potential use of the actinobacteria as the novel sources for the biosynthesis of nanoparticles with improved biomedical applications.

Ferromagnetic nanoparticles containing biologically active alkanolamines: preparation and properties

NASA Astrophysics Data System (ADS)

Segal, I.; Zablotskaya, A.; Lukevics, E.; Maiorov, M.; Zablotsky, D.

2005-12-01

The objective of the present study is to investigate the possibility of sorption on ultrafine magnetic particles of some model biologically active organosilicon alkanolamines, structural analogs of natural biologically active substances, choline and colamine, with increased lipophilicity. Double-coated ferromagnetic samples containing oleic acid, as a first layer, and organosilicon alcanolamines, as a second layer, were obtained and characterized by their physical/chemical (sorption and magnetisation) and biological (toxicity and cytotoxicity) properties. The present results clearly reveal the sorption of the biologically active alkanolamines on the surface of magnetic particles and a principal possibility to coat magnetite directly with biologically active alkanolamines, creating a mono-layer cover. The data presented in the study of cytotoxic properties of the newly obtained ferromagnetic nanoparticles show that it is reasonable to investigate such systems as potential cytotoxic agents. Tables 3, Figs 3, Refs 16.

Optical Antenna-Based Fluorescence Correlation Spectroscopy to Probe the Nanoscale Dynamics of Biological Membranes.

PubMed

Winkler, Pamina M; Regmi, Raju; Flauraud, Valentin; Brugger, Jürgen; Rigneault, Hervé; Wenger, Jérôme; García-Parajo, María F

2018-01-04

The plasma membrane of living cells is compartmentalized at multiple spatial scales ranging from the nano- to the mesoscale. This nonrandom organization is crucial for a large number of cellular functions. At the nanoscale, cell membranes organize into dynamic nanoassemblies enriched by cholesterol, sphingolipids, and certain types of proteins. Investigating these nanoassemblies known as lipid rafts is of paramount interest in fundamental cell biology. However, this goal requires simultaneous nanometer spatial precision and microsecond temporal resolution, which is beyond the reach of common microscopes. Optical antennas based on metallic nanostructures efficiently enhance and confine light into nanometer dimensions, breaching the diffraction limit of light. In this Perspective, we discuss recent progress combining optical antennas with fluorescence correlation spectroscopy (FCS) to monitor microsecond dynamics at nanoscale spatial dimensions. These new developments offer numerous opportunities to investigate lipid and protein dynamics in both mimetic and native biological membranes.

Late time cosmological dynamics with a nonminimal extension of the mimetic matter scenario

NASA Astrophysics Data System (ADS)

Hosseinkhan, N.; Nozari, K.

2018-02-01

We investigate an extension of mimetic gravity in which mimetic matter is nonminimally coupled to the Ricci scalar. We derive the background field equations and show that, as the minimal case, the nonminimal mimetic matter can behave as dark matter or dark energy. By adopting some well-known potentials, we study the dynamics of the scale factor and the equation of state parameter in detail. As the effective mimetic dark energy, this model explains the late time cosmic acceleration and its equation of state parameter crosses the phantom divide. We extend our analysis to the dynamical system approach and the phase space trajectories of the model. We obtain an attractor line which corresponds to the late time cosmic acceleration. By comparing this nonminimal mimetic matter scenario with observational data for the LCDM, we show that the confidence levels of this model overlap with those of Planck 2015 TT, TE, EE + Low P + Lensing + BAO data in the LCDM model.

The effect of biologically and chemically synthesized silver nanoparticles (AgNPs) on biofilm formation

NASA Astrophysics Data System (ADS)

Chojniak, Joanna; Biedroń, Izabela; Mendrek, Barbara; Płaza, Grażyna

2017-11-01

Bionanotechnology has emerged up as integration between biotechnology and nanotechnology for developing biosynthetic and environmental-friendly technology for synthesis of nanomaterials. Different types of nanomaterials like copper, zinc, titanium, magnesium, gold, and silver have applied in the various industries but silver nanoparticles have proved to be most effective against bacteria, viruses and eukaryotic microorganisms. The antimicrobial property of silver nanoparticles are widely known. Due to strong antibacterial property silver nanoparticles are used, e.g. in clothing, food industry, sunscreens, cosmetics and many household and environmental appliances. The aim of the study was to compare the effect of silver nanoparticles (AgNPs) synthesized biologically and chemically on the biofilm formation. The biofilm was formed by the bacteria isolated from the water supply network. The commonly used crystal violet assay (CV) was applied for biofilm analysis. In this study effect of biologically synthesized Ag-NPs on the biofilm formation was evaluated.

High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides.

PubMed

Uehara, Yoshinari; Chiesa, Giulia; Saku, Keijiro

2015-01-01

Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low-density lipoprotein (LDL) cholesterol and moderately increase that of plasma high-density lipoprotein (HDL) cholesterol. The reverse cholesterol transport pathway, mediated by HDL particles, has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is optimization of the HDL-cholesterol level and enhanced removal of plasma cholesterol, together with the prevention and mitigation of inflammation related to atherosclerosis. Small-molecule inhibitors of cholesteryl ester transfer protein (CETP) increase the HDL-cholesterol level in subjects with normal or low HDL-cholesterol. However, CETP inhibitors do not seem to reduce the risk of atherosclerotic diseases. HDL therapies using reconstituted HDL, including apolipoprotein (Apo) A-I Milano, ApoA-I mimetics, or full-length ApoA-I, are dramatically effective in animal models. Of those, the ApoA-I-mimetic peptide called FAMP effectively removes cholesterol via the ABCA1 transporter and acts as an antiatherosclerotic agent by enhancing the biological functions of HDL without elevating the HDL-cholesterol level. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases.

How Sound Symbolism Is Processed in the Brain: A Study on Japanese Mimetic Words

PubMed Central

Okuda, Jiro; Okada, Hiroyuki; Matsuda, Tetsuya

2014-01-01

Sound symbolism is the systematic and non-arbitrary link between word and meaning. Although a number of behavioral studies demonstrate that both children and adults are universally sensitive to sound symbolism in mimetic words, the neural mechanisms underlying this phenomenon have not yet been extensively investigated. The present study used functional magnetic resonance imaging to investigate how Japanese mimetic words are processed in the brain. In Experiment 1, we compared processing for motion mimetic words with that for non-sound symbolic motion verbs and adverbs. Mimetic words uniquely activated the right posterior superior temporal sulcus (STS). In Experiment 2, we further examined the generalizability of the findings from Experiment 1 by testing another domain: shape mimetics. Our results show that the right posterior STS was active when subjects processed both motion and shape mimetic words, thus suggesting that this area may be the primary structure for processing sound symbolism. Increased activity in the right posterior STS may also reflect how sound symbolic words function as both linguistic and non-linguistic iconic symbols. PMID:24840874

Catalytically and biologically active silver nanoparticles synthesized using essential oil

NASA Astrophysics Data System (ADS)

Vilas, Vidya; Philip, Daizy; Mathew, Joseph

2014-11-01

There are numerous reports on phytosynthesis of silver nanoparticles and various phytochemicals are involved in the reduction and stabilization. Pure explicit phytosynthetic protocol for catalytically and biologically active silver nanoparticles is of importance as it is an environmentally benign green method. This paper reports the use of essential oil of Myristica fragrans enriched in terpenes and phenyl propenes in the reduction and stabilization. FTIR spectra of the essential oil and the synthesized biogenic silver nanoparticles are in accordance with the GC-MS spectral analysis reports. Nanosilver is initially characterized by an intense SPR band around 420 nm, followed by XRD and TEM analysis revealing the formation of 12-26 nm sized, highly pure, crystalline silver nanoparticles. Excellent catalytic and bioactive potential of the silver nanoparticles is due to the surface modification. The chemocatalytic potential of nanosilver is exhibited by the rapid reduction of the organic pollutant, para nitro phenol and by the degradation of the thiazine dye, methylene blue. Significant antibacterial activity of the silver colloid against Gram positive, Staphylococcus aureus (inhibition zone - 12 mm) and Gram negative, Escherichia coli (inhibition zone - 14 mm) is demonstrated by Agar-well diffusion method. Strong antioxidant activity of the biogenic silver nanoparticles is depicted through NO scavenging, hydrogen peroxide scavenging, reducing power, DPPH and total antioxidant activity assays.

Mixed mimetic spectral element method for Stokes flow: A pointwise divergence-free solution

NASA Astrophysics Data System (ADS)

Kreeft, Jasper; Gerritsma, Marc

2013-05-01

In this paper we apply the recently developed mimetic discretization method to the mixed formulation of the Stokes problem in terms of vorticity, velocity and pressure. The mimetic discretization presented in this paper and in Kreeft et al. [51] is a higher-order method for curvilinear quadrilaterals and hexahedrals. Fundamental is the underlying structure of oriented geometric objects, the relation between these objects through the boundary operator and how this defines the exterior derivative, representing the grad, curl and div, through the generalized Stokes theorem. The mimetic method presented here uses the language of differential k-forms with k-cochains as their discrete counterpart, and the relations between them in terms of the mimetic operators: reduction, reconstruction and projection. The reconstruction consists of the recently developed mimetic spectral interpolation functions. The most important result of the mimetic framework is the commutation between differentiation at the continuous level with that on the finite dimensional and discrete level. As a result operators like gradient, curl and divergence are discretized exactly. For Stokes flow, this implies a pointwise divergence-free solution. This is confirmed using a set of test cases on both Cartesian and curvilinear meshes. It will be shown that the method converges optimally for all admissible boundary conditions.

Opuntia ficus indica peel derived pectin mediated hydroxyapatite nanoparticles: synthesis, spectral characterization, biological and antimicrobial activities.

PubMed

Gopi, D; Kanimozhi, K; Kavitha, L

2015-04-15

In the present study, we have adapted a facile and efficient green route for the synthesis of HAP nanoparticles using pectin as a template which was extracted from the peel of prickly pear (Opuntia ficus indica) fruits. The concentration of pectin plays a major role in the behavior of crystallinity, purity, morphology as well as biological property of the as-synthesized HAP nanoparticles. The extracted pectin and the as-synthesized nanoparticles were characterized by various analytical techniques. The in vitro apatite formation on the surface of the as-synthesized nanoparticles in simulated body fluid (SBF) for various days showed an enhanced bioactivity. Also, the antimicrobial activity was investigated using various microorganisms. All the results revealed the formation of pure, low crystalline and discrete granular like HAP nanoparticles of size around 25 nm with enhanced biological and antimicrobial activities. Hence the as-synthesized nanoparticles can act as a better bone regenerating material in the field of biomedicine. Copyright © 2015 Elsevier B.V. All rights reserved.

Opuntia ficus indica peel derived pectin mediated hydroxyapatite nanoparticles: Synthesis, spectral characterization, biological and antimicrobial activities

NASA Astrophysics Data System (ADS)

Gopi, D.; Kanimozhi, K.; Kavitha, L.

2015-04-01

In the present study, we have adapted a facile and efficient green route for the synthesis of HAP nanoparticles using pectin as a template which was extracted from the peel of prickly pear (Opuntia ficus indica) fruits. The concentration of pectin plays a major role in the behavior of crystallinity, purity, morphology as well as biological property of the as-synthesized HAP nanoparticles. The extracted pectin and the as-synthesized nanoparticles were characterized by various analytical techniques. The in vitro apatite formation on the surface of the as-synthesized nanoparticles in simulated body fluid (SBF) for various days showed an enhanced bioactivity. Also, the antimicrobial activity was investigated using various microorganisms. All the results revealed the formation of pure, low crystalline and discrete granular like HAP nanoparticles of size around 25 nm with enhanced biological and antimicrobial activities. Hence the as-synthesized nanoparticles can act as a better bone regenerating material in the field of biomedicine.

Female preferences drive the evolution of mimetic accuracy in male sexual displays.

PubMed

Coleman, Seth William; Patricelli, Gail Lisa; Coyle, Brian; Siani, Jennifer; Borgia, Gerald

2007-10-22

Males in many bird species mimic the vocalizations of other species during sexual displays, but the evolutionary and functional significance of interspecific vocal mimicry is unclear. Here we use spectrographic cross-correlation to compare mimetic calls produced by male satin bowerbirds (Ptilonorhynchus violaceus) in courtship with calls from several model species. We show that the accuracy of vocal mimicry and the number of model species mimicked are both independently related to male mating success. Multivariate analyses revealed that these mimetic traits were better predictors of male mating success than other male display traits previously shown to be important for male mating success. We suggest that preference-driven mimetic accuracy may be a widespread occurrence, and that mimetic accuracy may provide females with important information about male quality. Our findings support an alternative hypothesis to help explain a common element of male sexual displays.

Primordial cosmology in mimetic born-infeld gravity

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

Bouhmadi-Lopez, Mariam; Chen, Che -Yu; Chen, Pisin

Here, the Eddington-inspired-Born-Infeld (EiBI) model is reformulated within the mimetic approach. In the presence of a mimetic field, the model contains non-trivial vacuum solutions which could be free of spacetime singularity because of the Born-Infeld nature of the theory. We study a realistic primordial vacuum universe and prove the existence of regular solutions, such as primordial inflationary solutions of de Sitter type or bouncing solutions. Besides, the linear instabilities present in the EiBI model are found to be avoidable for some interesting bouncing solutions in which the physical metric as well as the auxiliary metric are regular at the backgroundmore » level.« less

Primordial cosmology in mimetic born-infeld gravity

DOE PAGES

Bouhmadi-Lopez, Mariam; Chen, Che -Yu; Chen, Pisin

2017-11-29

Here, the Eddington-inspired-Born-Infeld (EiBI) model is reformulated within the mimetic approach. In the presence of a mimetic field, the model contains non-trivial vacuum solutions which could be free of spacetime singularity because of the Born-Infeld nature of the theory. We study a realistic primordial vacuum universe and prove the existence of regular solutions, such as primordial inflationary solutions of de Sitter type or bouncing solutions. Besides, the linear instabilities present in the EiBI model are found to be avoidable for some interesting bouncing solutions in which the physical metric as well as the auxiliary metric are regular at the backgroundmore » level.« less

Dark-field-based observation of single-nanoparticle dynamics on a supported lipid bilayer for in situ analysis of interacting molecules and nanoparticles.

PubMed

Lee, Young Kwang; Kim, Sungi; Nam, Jwa-Min

2015-01-12

Observation of single plasmonic nanoparticles in reconstituted biological systems allows us to obtain snapshots of dynamic processes between molecules and nanoparticles with unprecedented spatiotemporal resolution and single-molecule/single-particle-level data acquisition. This Concept is intended to introduce nanoparticle-tethered supported lipid bilayer platforms that allow for the dynamic confinement of nanoparticles on a two-dimensional fluidic surface. The dark-field-based long-term, stable, real-time observation of freely diffusing plasmonic nanoparticles on a lipid bilayer enables one to extract a broad range of information about interparticle and molecular interactions throughout the entire reaction period. Herein, we highlight important developments in this context to provide ideas on how molecular interactions can be interpreted by monitoring dynamic behaviors and optical signals of laterally mobile nanoparticles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biologically and mechanically driven design of an RGD-mimetic macroporous foam for adipose tissue engineering applications.

PubMed

Rossi, Eleonora; Gerges, Irini; Tocchio, Alessandro; Tamplenizza, Margherita; Aprile, Paola; Recordati, Camilla; Martello, Federico; Martin, Ivan; Milani, Paolo; Lenardi, Cristina

2016-10-01

Despite clinical treatments for adipose tissue defects, in particular breast tissue reconstruction, have certain grades of efficacy, many drawbacks are still affecting the long-term survival of new formed fat tissue. To overcome this problem, in the last decades, several scaffolding materials have been investigated in the field of adipose tissue engineering. However, a strategy able to recapitulate a suitable environment for adipose tissue reconstruction and maintenance is still missing. To address this need, we adopted a biologically and mechanically driven design to fabricate an RGD-mimetic poly(amidoamine) oligomer macroporous foam (OPAAF) for adipose tissue reconstruction. The scaffold was designed to fulfil three fundamental criteria: capability to induce cell adhesion and proliferation, support of in vivo vascularization and match of native tissue mechanical properties. Poly(amidoamine) oligomers were formed into soft scaffolds with hierarchical porosity through a combined free radical polymerization and foaming reaction. OPAAF is characterized by a high water uptake capacity, progressive degradation kinetics and ideal mechanical properties for adipose tissue reconstruction. OPAAF's ability to support cell adhesion, proliferation and adipogenesis was assessed in vitro using epithelial, fibroblast and endothelial cells (MDCK, 3T3L1 and HUVEC respectively). In addition, in vivo subcutaneous implantation in murine model highlighted OPAAF potential to support both adipogenesis and vessels infiltration. Overall, the reported results support the use of OPAAF as a scaffold for engineered adipose tissue construct. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical and Biological Sensing Using Diatom Photonic Crystal Biosilica With In-Situ Growth Plasmonic Nanoparticles.

PubMed

Kong, Xianming; Squire, Kenny; Li, Erwen; LeDuff, Paul; Rorrer, Gregory L; Tang, Suning; Chen, Bin; McKay, Christopher P; Navarro-Gonzalez, Rafael; Wang, Alan X

2016-12-01

In this paper, we described a new type of bioenabled nano-plasmonic sensors based on diatom photonic crystal biosilica with in-situ growth silver nanoparticles and demonstrated label-free chemical and biological sensing based on surface-enhanced Raman scattering (SERs) from complex samples. Diatoms are photosynthetic marine micro-organisms that create their own skeletal shells of hydrated amorphous silica, called frustules, which possess photonic crystal-like hierarchical micro- & nanoscale periodic pores. Our research shows that such hybrid plasmonic-biosilica nanostructures formed by cost-effective and eco-friendly bottom-up processes can achieve ultra-high limit of detection for medical applications, food sensing, water/air quality monitoring and geological/space research. The enhanced sensitivity comes from the optical coupling of the guided-mode resonance of the diatom frustules and the localized surface plasmons of the silver nanoparticles. Additionally, the nanoporous, ultra-hydrophilic diatom biosilica with large surface-to-volume ratio can concentrate more analyte molecules to the surface of the SERS substrates, which can help to detect biomolecules that cannot be easily adsorbed by metallic nanoparticles.

Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in Biological Solutions.

PubMed

Robinson, Kye J; Huynh, Gabriel T; Kouskousis, Betty P; Fletcher, Nicholas L; Houston, Zachary H; Thurecht, Kristofer J; Corrie, Simon R

2018-04-19

Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5-8) with a response time of <100 ms, significantly faster than that of previously reported response times using silica-based particles. Particles produced stable, pH-specific signals when stored at room temperature for more than 80 days. Finally, we demonstrated that the nanosensors successfully monitored the pH of a bacterial culture over 15 h and that pH changes in the skin of mouse cadavers could also be observed via in vivo fluorescence imaging following subcutaneous injection. The understanding gained from linking sensor characteristics and material properties will inform the next generation of optical nanosensors for continuous-monitoring applications.

Protein Surface Mimetics: Understanding How Ruthenium Tris(Bipyridines) Interact with Proteins.

PubMed

Hewitt, Sarah H; Filby, Maria H; Hayes, Ed; Kuhn, Lars T; Kalverda, Arnout P; Webb, Michael E; Wilson, Andrew J

2017-01-17

Protein surface mimetics achieve high-affinity binding by exploiting a scaffold to project binding groups over a large area of solvent-exposed protein surface to make multiple cooperative noncovalent interactions. Such recognition is a prerequisite for competitive/orthosteric inhibition of protein-protein interactions (PPIs). This paper describes biophysical and structural studies on ruthenium(II) tris(bipyridine) surface mimetics that recognize cytochrome (cyt) c and inhibit the cyt c/cyt c peroxidase (CCP) PPI. Binding is electrostatically driven, with enhanced affinity achieved through enthalpic contributions thought to arise from the ability of the surface mimetics to make a greater number of noncovalent interactions than CCP with surface-exposed basic residues on cyt c. High-field natural abundance 1 H, 15 N HSQC NMR experiments are consistent with surface mimetics binding to cyt c in similar manner to CCP. This provides a framework for understanding recognition of proteins by supramolecular receptors and informing the design of ligands superior to the protein partners upon which they are inspired. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A review of underwater bio-mimetic propulsion: cruise and fast-start

NASA Astrophysics Data System (ADS)

Chao, Li-Ming; Cao, Yong-Hui; Pan, Guang

2017-08-01

This paper reviews recent developments in the understanding of underwater bio-mimetic propulsion. Two impressive models of underwater propulsion are considered: cruise and fast-start. First, we introduce the progression of bio-mimetic propulsion, especially underwater propulsion, where some primary conceptions are touched upon. Second, the understanding of flapping foils, considered as one of the most efficient cruise styles of aquatic animals, is introduced, where the effect of kinematics and the shape and flexibility of foils on generating thrust are elucidated respectively. Fast-start propulsion is always exhibited when predator behaviour occurs, and we provide an explicit introduction of corresponding zoological experiments and numerical simulations. We also provide some predictions about underwater bio-mimetic propulsion.

How can macromolecular crowding inhibit biological reactions? The enhanced formation of DNA nanoparticles

PubMed Central

Hou, Sen; Trochimczyk, Piotr; Sun, Lili; Wisniewska, Agnieszka; Kalwarczyk, Tomasz; Zhang, Xuzhu; Wielgus-Kutrowska, Beata; Bzowska, Agnieszka; Holyst, Robert

2016-01-01

In contrast to the already known effect that macromolecular crowding usually promotes biological reactions, solutions of PEG 6k at high concentrations stop the cleavage of DNA by HindIII enzyme, due to the formation of DNA nanoparticles. We characterized the DNA nanoparticles and probed the prerequisites for their formation using multiple techniques such as fluorescence correlation spectroscopy, dynamic light scattering, fluorescence analytical ultracentrifugation etc. In >25% PEG 6k solution, macromolecular crowding promotes the formation of DNA nanoparticles with dimensions of several hundreds of nanometers. The formation of DNA nanoparticles is a fast and reversible process. Both plasmid DNA (2686 bp) and double-stranded/single-stranded DNA fragment (66bp/nt) can form nanoparticles. We attribute the enhanced nanoparticle formation to the depletion effect of macromolecular crowding. This study presents our idea to enhance the formation of DNA nanoparticles by macromolecular crowding, providing the first step towards a final solution to efficient gene therapy. PMID:26903405

How can macromolecular crowding inhibit biological reactions? The enhanced formation of DNA nanoparticles.

PubMed

Hou, Sen; Trochimczyk, Piotr; Sun, Lili; Wisniewska, Agnieszka; Kalwarczyk, Tomasz; Zhang, Xuzhu; Wielgus-Kutrowska, Beata; Bzowska, Agnieszka; Holyst, Robert

2016-02-23

In contrast to the already known effect that macromolecular crowding usually promotes biological reactions, solutions of PEG 6k at high concentrations stop the cleavage of DNA by HindIII enzyme, due to the formation of DNA nanoparticles. We characterized the DNA nanoparticles and probed the prerequisites for their formation using multiple techniques such as fluorescence correlation spectroscopy, dynamic light scattering, fluorescence analytical ultracentrifugation etc. In >25% PEG 6k solution, macromolecular crowding promotes the formation of DNA nanoparticles with dimensions of several hundreds of nanometers. The formation of DNA nanoparticles is a fast and reversible process. Both plasmid DNA (2686 bp) and double-stranded/single-stranded DNA fragment (66 bp/nt) can form nanoparticles. We attribute the enhanced nanoparticle formation to the depletion effect of macromolecular crowding. This study presents our idea to enhance the formation of DNA nanoparticles by macromolecular crowding, providing the first step towards a final solution to efficient gene therapy.

An investigation of the mimetic enzyme activity of two-dimensional Pd-based nanostructures

NASA Astrophysics Data System (ADS)

Wei, Jingping; Chen, Xiaolan; Shi, Saige; Mo, Shiguang; Zheng, Nanfeng

2015-11-01

In this work, we investigated the mimetic enzyme activity of two-dimensional (2D) Pd-based nanostructures (e.g. Pd nanosheets, Pd@Au and Pd@Pt nanoplates) and found that they possess intrinsic peroxidase-, oxidase- and catalase-like activities. These nanostructures were able to activate hydrogen peroxide or dissolved oxygen for catalyzing the oxidation of organic substrates, and decompose hydrogen peroxide to generate oxygen. More systematic investigations revealed that the peroxidase-like activities of these Pd-based nanomaterials were highly structure- and composition-dependent. Among them, Pd@Pt nanoplates displayed the highest peroxidase-like activity. Based on these findings, Pd-based nanostructures were applied for the colorimetric detection of H2O2 and glucose, and also the electro-catalytic reduction of H2O2. This work offers a promising prospect for the application of 2D noble metal nanostructures in biocatalysis.In this work, we investigated the mimetic enzyme activity of two-dimensional (2D) Pd-based nanostructures (e.g. Pd nanosheets, Pd@Au and Pd@Pt nanoplates) and found that they possess intrinsic peroxidase-, oxidase- and catalase-like activities. These nanostructures were able to activate hydrogen peroxide or dissolved oxygen for catalyzing the oxidation of organic substrates, and decompose hydrogen peroxide to generate oxygen. More systematic investigations revealed that the peroxidase-like activities of these Pd-based nanomaterials were highly structure- and composition-dependent. Among them, Pd@Pt nanoplates displayed the highest peroxidase-like activity. Based on these findings, Pd-based nanostructures were applied for the colorimetric detection of H2O2 and glucose, and also the electro-catalytic reduction of H2O2. This work offers a promising prospect for the application of 2D noble metal nanostructures in biocatalysis. Electronic supplementary information (ESI) available: TEM images, EDX and dispersion stability of Pd-based nanomaterials

Conformation-Based Design and Synthesis of Apratoxin A Mimetics Modified at the α,β-Unsaturated Thiazoline Moiety.

PubMed

Onda, Yuichi; Masuda, Yuichi; Yoshida, Masahito; Doi, Takayuki

2017-08-10

We have demonstrated design, synthesis, and biological evaluation of apratoxin A mimetics. In the first generation, the moCys moiety was replaced with seven simple amino acids as their 3D structures can be similar to that of apratoxin A. Apratoxins M1-M7 were synthesized using solid-phase peptide synthesis and solution-phase macrolactamization. Apratoxin M7, which contains a piperidinecarboxylic acid moiety, exhibited potent cytotoxicity against HCT-116 cells. In the second generation, substitution of each amino acid residue in the tripeptide Tyr(Me)-MeAla-MeIle moiety in apratoxin M7 led to the development of the highly potent apratoxin M16 possessing biphenylalanine (Bph) instead of Tyr(Me), which exhibited an IC 50 value of 1.1 nM against HCT-116 cells. Moreover, compared to apratoxin A, apratoxin M16 exhibited a similarly high level of growth inhibitory activity against various cancer cell lines. The results indicate that apratoxin M16 could be a potential candidate as an anticancer agent.

Carbon nanoparticles as possible radioprotectors in biological systems

NASA Astrophysics Data System (ADS)

Krokosz, Anita; Lichota, Anna; Nowak, Katarzyna E.; Grebowski, Jacek

2016-11-01

Ionizing radiation causes radiolysis of water and the production of reactive oxygen species (ROS), which interact with biochemically important molecules in cells leading to cell death. In order to reduce the dangerous radiation effects on cells, tissues and organs, the search for radioprotectors is essential. ROS result in damage to biomolecules, e.g. proteins, lipids and DNA, and as a consequence, cause the loss of cell function. The chemical and biological properties of fullerenes and other carbon nanoparticles enable the possibility of generating either oxidative stress or its attenuation by both scavenging free radicals and modification/upregulation of endogenous antioxidative systems in cells. This study discusses the possible applications of carbon nanoparticles as radioprotective agents and/or free radical scavengers. Special attention is paid to water-soluble fullerenes as they are promising radioprotectors and exhibit low toxicity and cytotoxicity.

Elementary dispersion analysis of some mimetic discretizations on triangular C-grids

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

Korn, P., E-mail: peter.korn@mpimet.mpg.de; Danilov, S.; A.M. Obukhov Institute of Atmospheric Physics, Moscow

2017-02-01

Spurious modes supported by triangular C-grids limit their application for modeling large-scale atmospheric and oceanic flows. Their behavior can be modified within a mimetic approach that generalizes the scalar product underlying the triangular C-grid discretization. The mimetic approach provides a discrete continuity equation which operates on an averaged combination of normal edge velocities instead of normal edge velocities proper. An elementary analysis of the wave dispersion of the new discretization for Poincaré, Rossby and Kelvin waves shows that, although spurious Poincaré modes are preserved, their frequency tends to zero in the limit of small wavenumbers, which removes the divergence noisemore » in this limit. However, the frequencies of spurious and physical modes become close on shorter scales indicating that spurious modes can be excited unless high-frequency short-scale motions are effectively filtered in numerical codes. We argue that filtering by viscous dissipation is more efficient in the mimetic approach than in the standard C-grid discretization. Lumping of mass matrices appearing with the velocity time derivative in the mimetic discretization only slightly reduces the accuracy of the wave dispersion and can be used in practice. Thus, the mimetic approach cures some difficulties of the traditional triangular C-grid discretization but may still need appropriately tuned viscosity to filter small scales and high frequencies in solutions of full primitive equations when these are excited by nonlinear dynamics.« less

René Girard and the Mimetic Nature of Eating Disorders.

PubMed

Strand, Mattias

2018-03-07

French historian and literary critic René Girard (1923-2015), most widely known for the concepts of mimetic desire and scapegoating, also engaged in the discussion of the surge of eating disorders in his 1996 essay Eating Disorders and Mimetic Desire. This article explores Girard's ideas on the mimetic nature and origin of eating disorders from a clinical psychiatric perspective and contextualizes them within the field of eating disorders research as well as in relation to broader psychological, sociological and anthropological models of social comparison and non-consumption. Three main themes in Girard's thinking on the topic of eating disorders are identified and explored: the 'end of prohibitions' as a driving force in the emergence of eating disorders, eating disorders as a phenomenon specific to modernity, and the significance of 'conspicuous non-consumption' in the emergence of eating disorders.

Elution of Labile Fluorescent Dye from Nanoparticles during Biological Use

PubMed Central

Tenuta, Tiziana; Monopoli, Marco P.; Kim, JongAh; Salvati, Anna; Dawson, Kenneth A.; Sandin, Peter; Lynch, Iseult

2011-01-01

Cells act as extremely efficient filters for elution of unbound fluorescent tags or impurities associated with nanoparticles, including those that cannot be removed by extensive cleaning. This has consequences for quantification of nanoparticle uptake and sub-cellular localization in vitro and in vivo as a result of the presence of significant amount of labile dye even following extensive cleaning by dialysis. Polyacrylamide gel electrophoresis (PAGE) can be used to monitor the elution of unbound fluorescent probes from nanoparticles, either commercially available or synthesized in-house, and to ensure their complete purification for biological studies, including cellular uptake and sub-cellular localisation. Very different fluorescence distribution within cells is observed after short dialysis times versus following extensive dialysis against a solvent in which the free dye is more soluble, due to the contribution from free dye. In the absence of an understanding of the presence of residual free dye in (most) labeled nanoparticle solutions, the total fluorescence intensity in cells following exposure to nanoparticle solutions could be mis-ascribed to the presence of nanoparticles through the cell, rather than correctly assigned to either a combination of free-dye and nanoparticle-bound dye, or even entirely to free dye depending on the exposure conditions (i.e. aggregation of the particles etc). Where all of the dye is nanoparticle-bound, the particles are highly localized in sub-cellular organelles, likely lysosomes, whereas in a system containing significant amounts of free dye, the fluorescence is distributed through the cell due to the free diffusion of the molecule dye across all cellular barriers and into the cytoplasm. PMID:21998668

Extended mimetic gravity: Hamiltonian analysis and gradient instabilities

NASA Astrophysics Data System (ADS)

Takahashi, Kazufumi; Kobayashi, Tsutomu

2017-11-01

We propose a novel class of degenerate higher-order scalar-tensor theories as an extension of mimetic gravity. By performing a noninvertible conformal transformation on "seed" scalar-tensor theories which may be nondegenerate, we can generate a large class of theories with at most three physical degrees of freedom. We identify a general seed theory for which this is possible. Cosmological perturbations in these extended mimetic theories are also studied. It is shown that either of tensor or scalar perturbations is plagued with gradient instabilities, except for a special case where the scalar perturbations are presumably strongly coupled, or otherwise there appear ghost instabilities.

Nanoparticle solutions as adhesives for gels and biological tissues

NASA Astrophysics Data System (ADS)

Rose, Séverine; Prevoteau, Alexandre; Elzière, Paul; Hourdet, Dominique; Marcellan, Alba; Leibler, Ludwik

2014-01-01

Adhesives are made of polymers because, unlike other materials, polymers ensure good contact between surfaces by covering asperities, and retard the fracture of adhesive joints by dissipating energy under stress. But using polymers to `glue' together polymer gels is difficult, requiring chemical reactions, heating, pH changes, ultraviolet irradiation or an electric field. Here we show that strong, rapid adhesion between two hydrogels can be achieved at room temperature by spreading a droplet of a nanoparticle solution on one gel's surface and then bringing the other gel into contact with it. The method relies on the nanoparticles' ability to adsorb onto polymer gels and to act as connectors between polymer chains, and on the ability of polymer chains to reorganize and dissipate energy under stress when adsorbed onto nanoparticles. We demonstrate this approach by pressing together pieces of hydrogels, for approximately 30 seconds, that have the same or different chemical properties or rigidities, using various solutions of silica nanoparticles, to achieve a strong bond. Furthermore, we show that carbon nanotubes and cellulose nanocrystals that do not bond hydrogels together become adhesive when their surface chemistry is modified. To illustrate the promise of the method for biological tissues, we also glued together two cut pieces of calf's liver using a solution of silica nanoparticles. As a rapid, simple and efficient way to assemble gels or tissues, this method is desirable for many emerging technological and medical applications such as microfluidics, actuation, tissue engineering and surgery.

Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles

NASA Astrophysics Data System (ADS)

Kishimoto, Takashi K.; Ferrari, Joseph D.; Lamothe, Robert A.; Kolte, Pallavi N.; Griset, Aaron P.; O'Neil, Conlin; Chan, Victor; Browning, Erica; Chalishazar, Aditi; Kuhlman, William; Fu, Fen-Ni; Viseux, Nelly; Altreuter, David H.; Johnston, Lloyd; Maldonado, Roberto

2016-10-01

The development of antidrug antibodies (ADAs) is a common cause for the failure of biotherapeutic treatments and adverse hypersensitivity reactions. Here we demonstrate that poly(lactic-co-glycolic acid) (PLGA) nanoparticles carrying rapamycin, but not free rapamycin, are capable of inducing durable immunological tolerance to co-administered proteins that is characterized by the induction of tolerogenic dendritic cells, an increase in regulatory T cells, a reduction in B cell activation and germinal centre formation, and the inhibition of antigen-specific hypersensitivity reactions. Intravenous co-administration of tolerogenic nanoparticles with pegylated uricase inhibited the formation of ADAs in mice and non-human primates and normalized serum uric acid levels in uricase-deficient mice. Similarly, the subcutaneous co-administration of nanoparticles with adalimumab resulted in the durable inhibition of ADAs, leading to normalized pharmacokinetics of the anti-TNFα antibody and protection against arthritis in TNFα transgenic mice. Adjunct therapy with tolerogenic nanoparticles represents a novel and broadly applicable approach to prevent the formation of ADAs against biologic therapies.

Microfluidics-based in vivo mimetic systems for the study of cellular biology.

PubMed

Kim, Donghyuk; Wu, Xiaojie; Young, Ashlyn T; Haynes, Christy L

2014-04-15

The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system's components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years

Chemomics-based marker compounds mining and mimetic processing for exploring chemical mechanisms in traditional processing of herbal medicines, a continuous study on Rehmanniae Radix.

PubMed

Zhou, Li; Xu, Jin-Di; Zhou, Shan-Shan; Shen, Hong; Mao, Qian; Kong, Ming; Zou, Ye-Ting; Xu, Ya-Yun; Xu, Jun; Li, Song-Lin

2017-12-29

Exploring processing chemistry, in particular the chemical transformation mechanisms involved, is a key step to elucidate the scientific basis in traditional processing of herbal medicines. Previously, taking Rehmanniae Radix (RR) as a case study, the holistic chemome (secondary metabolome and glycome) difference between raw and processed RR was revealed by integrating hyphenated chromatographic techniques-based targeted glycomics and untargeted metabolomics. Nevertheless, the complex chemical transformation mechanisms underpinning the holistic chemome variation in RR processing remain to be extensively clarified. As a continuous study, here a novel strategy by combining chemomics-based marker compounds mining and mimetic processing is proposed for further exploring the chemical mechanisms involved in herbal processing. First, the differential marker compounds between raw and processed herbs were rapidly discovered by untargeted chemomics-based mining approach through multivariate statistical analysis of the chemome data obtained by integrated metabolomics and glycomics analysis. Second, the marker compounds were mimetically processed under the simulated physicochemical conditions as in the herb processing, and the final reaction products were chemically characterized by targeted chemomics-based mining approach. Third, the main chemical transformation mechanisms involved were clarified by linking up the original marker compounds and their mimetic processing products. Using this strategy, a set of differential marker compounds including saccharides, glycosides and furfurals in raw and processed RR was rapidly found, and the major chemical mechanisms involved in RR processing were elucidated as stepwise transformations of saccharides (polysaccharides, oligosaccharides and monosaccharides) and glycosides (iridoid glycosides and phenethylalcohol glycosides) into furfurals (glycosylated/non-glycosylated hydroxymethylfurfurals) by deglycosylation and/or dehydration. The

Functional Mimetics of the HIV-1 CCR5 Co-Receptor Displayed on the Surface of Magnetic Liposomes.

PubMed

Kuzmina, Alona; Vaknin, Karin; Gdalevsky, Garik; Vyazmensky, Maria; Marks, Robert S; Taube, Ran; Engel, Stanislav

2015-01-01

Chemokine G protein coupled receptors, principally CCR5 or CXCR4, function as co-receptors for HIV-1 entry into CD4+ T cells. Initial binding of the viral envelope glycoprotein (Env) gp120 subunit to the host CD4 receptor induces a cascade of structural conformational changes that lead to the formation of a high-affinity co-receptor-binding site on gp120. Interaction between gp120 and the co-receptor leads to the exposure of epitopes on the viral gp41 that mediates fusion between viral and cell membranes. Soluble CD4 (sCD4) mimetics can act as an activation-based inhibitor of HIV-1 entry in vitro, as it induces similar structural changes in gp120, leading to increased virus infectivity in the short term but to virus Env inactivation in the long term. Despite promising clinical implications, sCD4 displays low efficiency in vivo, and in multiple HIV strains, it does not inhibit viral infection. This has been attributed to the slow kinetics of the sCD4-induced HIV Env inactivation and to the failure to obtain sufficient sCD4 mimetic levels in the serum. Here we present uniquely structured CCR5 co-receptor mimetics. We hypothesized that such mimetics will enhance sCD4-induced HIV Env inactivation and inhibition of HIV entry. Co-receptor mimetics were derived from CCR5 gp120-binding epitopes and functionalized with a palmitoyl group, which mediated their display on the surface of lipid-coated magnetic beads. CCR5-peptidoliposome mimetics bound to soluble gp120 and inhibited HIV-1 infectivity in a sCD4-dependent manner. We concluded that CCR5-peptidoliposomes increase the efficiency of sCD4 to inhibit HIV infection by acting as bait for sCD4-primed virus, catalyzing the premature discharge of its fusion potential.

Functional Mimetics of the HIV-1 CCR5 Co-Receptor Displayed on the Surface of Magnetic Liposomes

PubMed Central

Kuzmina, Alona; Vaknin, Karin; Gdalevsky, Garik; Vyazmensky, Maria; Marks, Robert S.; Taube, Ran

2015-01-01

Chemokine G protein coupled receptors, principally CCR5 or CXCR4, function as co-receptors for HIV-1 entry into CD4+ T cells. Initial binding of the viral envelope glycoprotein (Env) gp120 subunit to the host CD4 receptor induces a cascade of structural conformational changes that lead to the formation of a high-affinity co-receptor-binding site on gp120. Interaction between gp120 and the co-receptor leads to the exposure of epitopes on the viral gp41 that mediates fusion between viral and cell membranes. Soluble CD4 (sCD4) mimetics can act as an activation-based inhibitor of HIV-1 entry in vitro, as it induces similar structural changes in gp120, leading to increased virus infectivity in the short term but to virus Env inactivation in the long term. Despite promising clinical implications, sCD4 displays low efficiency in vivo, and in multiple HIV strains, it does not inhibit viral infection. This has been attributed to the slow kinetics of the sCD4-induced HIV Env inactivation and to the failure to obtain sufficient sCD4 mimetic levels in the serum. Here we present uniquely structured CCR5 co-receptor mimetics. We hypothesized that such mimetics will enhance sCD4-induced HIV Env inactivation and inhibition of HIV entry. Co-receptor mimetics were derived from CCR5 gp120-binding epitopes and functionalized with a palmitoyl group, which mediated their display on the surface of lipid-coated magnetic beads. CCR5-peptidoliposome mimetics bound to soluble gp120 and inhibited HIV-1 infectivity in a sCD4-dependent manner. We concluded that CCR5-peptidoliposomes increase the efficiency of sCD4 to inhibit HIV infection by acting as bait for sCD4-primed virus, catalyzing the premature discharge of its fusion potential. PMID:26629902

Optical assays based on colloidal inorganic nanoparticles.

PubMed

Ghasemi, Amir; Rabiee, Navid; Ahmadi, Sepideh; Hashemzadeh, Shabnam; Lolasi, Farshad; Bozorgomid, Mahnaz; Kalbasi, Alireza; Nasseri, Behzad; Shiralizadeh Dezfuli, Amin; Aref, Amir Reza; Karimi, Mahdi; Hamblin, Michael R

2018-06-20

Colloidal inorganic nanoparticles have wide applications in the detection of analytes and in biological assays. A large number of these assays rely on the ability of gold nanoparticles (AuNPs, in the 20 nm diameter size range) to undergo a color change from red to blue upon aggregation. AuNP assays can be based on cross-linking, non-cross linking or unmodified charge-based aggregation. Nucleic acid-based probes, monoclonal antibodies, and molecular-affinity agents can be attached by covalent or non-covalent means. Surface plasmon resonance and SERS techniques can be utilized. Silver NPs also have attractive optical properties (higher extinction coefficient). Combinations of AuNPs and AgNPs in nanocomposites can have additional advantages. Magnetic NPs and ZnO, TiO2 and ZnS as well as insulator NPs including SiO2 can be employed in colorimetric assays, and some can act as peroxidase mimics in catalytic applications. This review covers the synthesis and stabilization of inorganic NPs and their diverse applications in colorimetric and optical assays for analytes related to environmental contamination (metal ions and pesticides), and for early diagnosis and monitoring of diseases, using medically important biomarkers.

A framework for developing a mimetic tensor artificial viscosity for Lagrangian hydrocodes on arbitrary polygonal and polyhedral meshes (u)

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

Lipnikov, Konstantin; Shashkov, Mikhail

2011-01-11

We construct a new mimetic tensor artificial viscosity on general polygonal and polyhedral meshes. The tensor artificial viscosity is based on a mimetic discretization of coordinate invariant operators, divergence of a tensor and gradient of a vector. The focus of this paper is on the symmetric form, div ({mu},{var_epsilon}(u)), of the tensor artificial viscosity where {var_epsilon}(u) is the symmetrized gradient of u and {mu}, is a tensor. The mimetic discretizations of this operator is derived for the case of a full tensor coefficient {mu}, that may reflect a shock direction. We demonstrate performance of the new viscosity for the Nohmore » implosion, Sedov explosion and Saltzman piston problems in both Cartesian and axisymmetric coordinate systems.« less

Dormancy as exaptation to protect mimetic seeds against deterioration before dispersal

PubMed Central

Brancalion, Pedro H. S.; Novembre, Ana D. L. C.; Rodrigues, Ricardo R.; Marcos Filho, Júlio

2010-01-01

Background and Aims Mimetic seeds simulate the appearance of fleshy fruits and arilled seeds without producing nutritive tissues as a reward for seed dispersers. In this strategy of seed dispersal, seeds may remain attached to the mother plant for long periods after maturity, increasing their availability to naïve seed dispersers. The hypothesis that seed coat impermeability in many tropical Fabaceae with mimetic seeds serves as an exaptation to protect the seeds from deterioration and rotting while awaiting dispersal was investigated. Methods Seed coat impermeability was evaluated in five mimetic-seeded species of tropical Fabaceae in south-eastern Brazil (Abarema langsdorffii, Abrus precatorius, Adenanthera pavonina, Erythrina velutina and Ormosia arborea) and in Erythrina speciosa, a ‘basal’ species in its genus, which has monochromatic brown seeds and no mimetic displays. Seed hardness was evaluated as a defence against accelerated ageing (humid chamber at 41 °C for 144 h). Seed development and physiological potential of O. arborea was evaluated and the effect of holding mature seeds in pods on the mother plant in the field for a period of 1 year under humid tropical conditions was compared with seeds stored under controlled conditions (15 °C and 40 % relative air humidity). Key Results All five mimetic-seeded species, and E. speciosa, showed strong coat impermeability, which protected the seeds against deterioration in accelerated ageing. Most O. arborea seeds only became dormant 2 months after pod dehiscence. Germination of seeds after 1 year on the plant in a humid tropical climate was 56 %, compared with 80 % for seeds stored in controlled conditions (15 °C, 45 % relative humidity). Seedling shoot length after 1 year did not differ between seed sources. Conclusions Dormancy acts in mimetic-seeded species as an exaptation to reduce seed deterioration, allowing an increase in their effective dispersal period and mitigating the losses incurred by low

Microfluidics-Based in Vivo Mimetic Systems for the Study of Cellular Biology

PubMed Central

2015-01-01

Conspectus The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system’s components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the

Nanoparticles based fiber optic SPR sensor

NASA Astrophysics Data System (ADS)

Shah, Kruti; Sharma, Navneet K.

2018-05-01

Localized surface plasmon resonance based fiber optic sensor using platinum nanoparticles is proposed and theoretically analyzed. Increase in thickness of nanoparticles layer increases the sensitivity of sensor. 50 nm thick platinum nanoparticles layer based sensor reveals highest sensitivity.

Biological consequences of nanoscale energy deposition near irradiated heavy atom nanoparticles

PubMed Central

McMahon, Stephen J.; Hyland, Wendy B.; Muir, Mark F.; Coulter, Jonathan A.; Jain, Suneil; Butterworth, Karl T.; Schettino, Giuseppe; Dickson, Glenn R.; Hounsell, Alan R.; O'Sullivan, Joe M.; Prise, Kevin M.; Hirst, David G.; Currell, Fred J.

2011-01-01

Gold nanoparticles (GNPs) are being proposed as contrast agents to enhance X-ray imaging and radiotherapy, seeking to take advantage of the increased X-ray absorption of gold compared to soft tissue. However, there is a great discrepancy between physically predicted increases in X-ray energy deposition and experimentally observed increases in cell killing. In this work, we present the first calculations which take into account the structure of energy deposition in the nanoscale vicinity of GNPs and relate this to biological outcomes, and show for the first time good agreement with experimentally observed cell killing by the combination of X-rays and GNPs. These results are not only relevant to radiotherapy, but also have implications for applications of heavy atom nanoparticles in biological settings or where human exposure is possible because the localised energy deposition high-lighted by these results may cause complex DNA damage, leading to mutation and carcinogenesis. PMID:22355537

CD4 mimetics sensitize HIV-1-infected cells to ADCC.

PubMed

Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B; Park, Jongwoo; Jones, David M; Courter, Joel R; Melillo, Bruno N; Kaufmann, Daniel E; Hahn, Beatrice H; Permar, Sallie R; Haynes, Barton F; Madani, Navid; Sodroski, Joseph G; Finzi, Andrés

2015-05-19

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.

CD4 mimetics sensitize HIV-1-infected cells to ADCC

PubMed Central

Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S.; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B.; Park, Jongwoo; Jones, David M.; Courter, Joel R.; Melillo, Bruno N.; Kaufmann, Daniel E.; Hahn, Beatrice H.; Permar, Sallie R.; Haynes, Barton F.; Madani, Navid; Sodroski, Joseph G.; Finzi, Andrés

2015-01-01

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection. PMID:25941367

Luminescence of colloidal ZnO nanoparticles synthesized in alcohols and biological application of ZnO passivated by MgO.

PubMed

Sikora, Bożena; Fronc, Krzysztof; Kamińska, Izabela; Koper, Kamil; Stępień, Piotr; Elbaum, Danek

2013-05-15

This report presents the results of spectroscopic measurements of colloidal ZnO nanoparticles synthesized in various alcohols. Luminescence of colloidal ZnO was monitored under different reaction conditions to elucidate the mechanism of the visible emission. We performed the process in different alcohols, temperatures and reaction times for two different reactants: water and NaOH. Based on the presented and previously published results it is apparent that the luminescence of the nanoparticles is influenced by several competing phenomena: the formation of new nucleation centers, the growth of the nanoparticles and surface passivation. Superimposed on the above effects is a size dependent luminescence alteration resulting from the quantum confinement. The study contributes to our understanding of the origin of ZnO nanoparticles' green emission which is important in a rational design of fluorescent probes for nontoxic biological applications. The ZnO nanoparticles were coated with a magnesium oxide layer and introduced into a HeLa cancer cell.

Collagen-binding VEGF mimetic peptide: Structure, matrix interaction, and endothelial cell activation

NASA Astrophysics Data System (ADS)

Chan, Tania R.

Long term survival of artificial tissue constructs depends greatly on proper vascularization. In nature, differentiation of endothelial cells and formation of vasculature are directed by dynamic spatio-temporal cues in the extracellular matrix that are difficult to reproduce in vitro. In this dissertation, we present a novel bifunctional peptide that mimics matrix-bound vascular endothelial growth factor (VEGF), which can be used to encode spatially controlled angiogenic signals in collagen-based scaffolds. The peptide, QKCMP, contains a collagen mimetic domain (CMP) that binds to type I collagen by a unique triple helix hybridization mechanism and a VEGF mimetic domain (QK) with pro-angiogenic activity. We demonstrate QKCMP's ability to hybridize with native and heat denatured collagens through a series of binding studies on collagen and gelatin substrates. Circular dichroism experiments show that the peptide retains the triple helical structure vital for collagen binding, and surface plasmon resonance study confirms the molecular interaction between the peptide and collagen strands. Cell culture studies demonstrate QKCMP's ability to induce endothelial cell morphogenesis and network formation as a matrix-bound factor in 2D and 3D collagen scaffolds. We also show that the peptide can be used to spatially modify collagen-based substrates to promote localized endothelial cell activation and network formation. To probe the biological events that govern these angiogenic cellular responses, we investigated the cell signaling pathways activated by collagen-bound QKCMP and determined short and long-term endothelial cell response profiles for p38, ERK1/2, and Akt signal transduction cascades. Finally, we present our efforts to translate the peptide's in vitro bioactivity to an in vivo burn injury animal model. When implanted at the wound site, QKCMP functionalized biodegradable hydrogels induce enhanced neovascularization in the granulation tissue. The results show QKCMP

Alterations in nanoparticle protein corona by biological surfactants: impact of bile salts on β-lactoglobulin-coated gold nanoparticles.

PubMed

Winuprasith, Thunnalin; Chantarak, Sirinya; Suphantharika, Manop; He, Lili; McClements, David Julian

2014-07-15

The impact of biological surfactants (bile salts) on the protein (β-lactoglobulin) corona surrounding gold nanoparticles (200 nm) was studied using a variety of analytical techniques at pH 7: dynamic light scattering (DLS); particle electrophoresis (ζ-potential); UV-visible (UV) spectroscopy; transmission electron microscopy (TEM); and surface-enhanced Raman scattering (SERS). The bile salts adsorbed to the protein-coated nanoparticle surfaces and altered their interfacial composition, charge, and structure. SERS spectra of protein-coated nanoparticles after bile salt addition contained bands from both protein and bile salts, indicating that the protein was not fully displaced by the bile salts. UV, DLS and TEM techniques also indicated that the protein coating was not fully displaced from the nanoparticle surfaces. The impact of bile salts could be described by an orogenic mechanism: mixed interfaces were formed that consisted of islands of aggregated proteins surrounded by a sea of bile salts. This knowledge is useful for understanding the interactions of bile salts with protein-coated colloidal particles, which may be important for controlling the fate of colloidal delivery systems in the human gastrointestinal tract, or the gastrointestinal fate of ingested inorganic nanoparticles. Copyright © 2014 Elsevier Inc. All rights reserved.

Networks of gold nanoparticles and bacteriophage as biological sensors and cell-targeting agents

PubMed Central

Souza, Glauco R.; Christianson, Dawn R.; Staquicini, Fernanda I.; Ozawa, Michael G.; Snyder, Evan Y.; Sidman, Richard L.; Miller, J. Houston; Arap, Wadih; Pasqualini, Renata

2006-01-01

Biological molecular assemblies are excellent models for the development of nanoengineered systems with desirable biomedical properties. Here we report an approach for fabrication of spontaneous, biologically active molecular networks consisting of bacteriophage (phage) directly assembled with gold (Au) nanoparticles (termed Au–phage). We show that when the phage are engineered so that each phage particle displays a peptide, such networks preserve the cell surface receptor binding and internalization attributes of the displayed peptide. The spontaneous organization of these targeted networks can be manipulated further by incorporation of imidazole (Au–phage–imid), which induces changes in fractal structure and near-infrared optical properties. The networks can be used as labels for enhanced fluorescence and dark-field microscopy, surface-enhanced Raman scattering detection, and near-infrared photon-to-heat conversion. Together, the physical and biological features within these targeted networks offer convenient multifunctional integration within a single entity with potential for nanotechnology-based biomedical applications. PMID:16434473

Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line

NASA Astrophysics Data System (ADS)

Han, Jae Woong; Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Choi, Yun-Jung; Kwon, Deug-Nam; Park, Jin-Ki; Kim, Jin-Hoi

2014-09-01

The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate . The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles.

Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line

PubMed Central

2014-01-01

The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate. The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles. PMID:25242904

Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation.

PubMed

Zhao, Jing; Zhang, Lei; Mu, Xiaodong; Doebelin, Christelle; Nguyen, William; Wallace, Callen; Reay, Daniel P; McGowan, Sara J; Corbo, Lana; Clemens, Paula R; Wilson, Gabriela Mustata; Watkins, Simon C; Solt, Laura A; Cameron, Michael D; Huard, Johnny; Niedernhofer, Laura J; Kamenecka, Theodore M; Robbins, Paul D

2018-06-11

Nuclear factor κB (NF-κB) is a transcription factor important for regulating innate and adaptive immunity, cellular proliferation, apoptosis, and senescence. Dysregulation of NF-κB and its upstream regulator IκB kinase (IKK) contributes to the pathogenesis of multiple inflammatory and degenerative diseases as well as cancer. An 11-amino acid peptide containing the NF-κB essential modulator (NEMO)-binding domain (NBD) derived from the C-terminus of β subunit of IKK, functions as a highly selective inhibitor of the IKK complex by disrupting the association of IKKβ and the IKKγ subunit NEMO. A structure-based pharmacophore model was developed to identify NBD mimetics by in silico screening. Two optimized lead NBD mimetics, SR12343 and SR12460, inhibited tumor necrosis factor α (TNF-α)- and lipopolysaccharide (LPS)-induced NF-κB activation by blocking the interaction between IKKβ and NEMO and suppressed LPS-induced acute pulmonary inflammation in mice. Chronic treatment of a mouse model of Duchenne muscular dystrophy (DMD) with SR12343 and SR12460 attenuated inflammatory infiltration, necrosis and muscle degeneration, demonstrating that these small-molecule NBD mimetics are potential therapeutics for inflammatory and degenerative diseases.

Atomic force microscopy of adsorbed proteoglycan mimetic nanoparticles: Toward new glycocalyx-mimetic model surfaces.

PubMed

Hedayati, Mohammadhasan; Kipper, Matt J

2018-06-15

Blood vessels present a dense, non-uniform, polysaccharide-rich layer, called the endothelial glycocalyx. The polysaccharides in the glycocalyx include polyanionic glycosaminoglycans (GAGs). This polysaccharide-rich surface has excellent and unique blood compatibility. We report new methods for preparing and characterizing dense GAG surfaces that can serve as models of the vascular endothelial glycocalyx. The GAG-rich surfaces are prepared by adsorbing heparin or chondroitin sulfate-containing polyelectrolyte complex nanoparticles (PCNs) to chitosan-hyaluronan polyelectrolyte multilayers (PEMs). The surfaces are characterized by PeakForce tapping atomic force microscopy, both in air and in aqueous pH 7.4 buffer, and by PeakForce quantitative nanomechanics (PF-QNM) mode with high spatial resolution. These new surfaces provide access to heparin-rich or chondroitin sulfate-rich coatings that mimic both composition and nanoscale structural features of the vascular endothelial glycocalyx. Copyright © 2018. Published by Elsevier Ltd.

“Turn-on” fluorescence probe integrated polymer nanoparticles for sensing biological thiol molecules

NASA Astrophysics Data System (ADS)

Ang, Chung Yen; Tan, Si Yu; Lu, Yunpeng; Bai, Linyi; Li, Menghuan; Li, Peizhou; Zhang, Quan; Selvan, Subramanian Tamil; Zhao, Yanli

2014-11-01

A ``turn-on'' thiol-responsive fluorescence probe was synthesized and integrated into polymeric nanoparticles for sensing intracellular thiols. There is a photo-induced electron transfer process in the off state of the probe, and this process is terminated upon the reaction with thiol compounds. Configuration interaction singles (CIS) calculation was performed to confirm the mechanism of this process. A series of sensing studies were carried out, showing that the probe-integrated nanoparticles were highly selective towards biological thiol compounds over non-thiolated amino acids. Kinetic studies were also performed to investigate the relative reaction rate between the probe and the thiolated amino acids. Subsequently, the Gibbs free energy of the reactions was explored by means of the electrochemical method. Finally, the detection system was employed for sensing intracellular thiols in cancer cells, and the sensing selectivity could be further enhanced with the use of a cancer cell-targeting ligand in the nanoparticles. This development paves a path for the sensing and detection of biological thiols, serving as a potential diagnostic tool in the future.

Environmental transformations and ecological effects of iron-based nanoparticles.

PubMed

Lei, Cheng; Sun, Yuqing; Tsang, Daniel C W; Lin, Daohui

2018-01-01

The increasing application of iron-based nanoparticles (NPs), especially high concentrations of zero-valent iron nanoparticles (nZVI), has raised concerns regarding their environmental behavior and potential ecological effects. In the environment, iron-based NPs undergo physical, chemical, and/or biological transformations as influenced by environmental factors such as pH, ions, dissolved oxygen, natural organic matter (NOM), and biotas. This review presents recent research advances on environmental transformations of iron-based NPs, and articulates their relationships with the observed toxicities. The type and extent of physical, chemical, and biological transformations, including aggregation, oxidation, and bio-reduction, depend on the properties of NPs and the receiving environment. Toxicities of iron-based NPs to bacteria, algae, fish, and plants are increasingly observed, which are evaluated with a particular focus on the underlying mechanisms. The toxicity of iron-based NPs is a function of their properties, tolerance of test organisms, and environmental conditions. Oxidative stress induced by reactive oxygen species is considered as the primary toxic mechanism of iron-based NPs. Factors influencing the toxicity of iron-based NPs are addressed and environmental transformations play a significant role, for example, surface oxidation or coating by NOM generally lowers the toxicity of nZVI. Research gaps and future directions are suggested with an aim to boost concerted research efforts on environmental transformations and toxicity of iron-based NPs, e.g., toxicity studies of transformed NPs in field, expansion of toxicity endpoints, and roles of laden contaminants and surface coating. This review will enhance our understanding of potential risks of iron-based NPs and proper uses of environmentally benign NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relevance of protein-protein interactions on the biological identity of nanoparticles.

PubMed

Vasti, Cecilia; Bonnet, Laura V; Galiano, Mauricio R; Rojas, Ricardo; Giacomelli, Carla E

2018-06-01

Considering that the use of nanoparticles (NPs) as carriers of therapeutic or theranostic agents has increased in the last years, it is mandatory to understand the interaction between NPs and living systems. In contact with biological fluids, the NPs (synthetic identity) are covered with biomolecules that form a protein corona, which defines the biological identity. It is well known that the protein corona formation is mediated by non-specific physical interactions, but protein-protein interactions (PPI), involving specific recognition sites of the polypeptides, are also involved. This work explores the relationship between the synthetic and biological identities of layered double hydroxides nanoparticles (LDH-NPs) and the effect of the protein corona on the cellular response. With such a purpose, the synthetic identity was modified by coating LDH-NPs with either a single protein or a complex mixture of them, followed by the characterization of the protein corona formed in a commonly used cell culture medium. A proteomic approach was used to identify the protein corona molecules and the PPI network was constructed with a novel bioinformatic tool. The coating on LDH-NPs defines the biological identity in such a way that the composition of the protein corona as well as PPI are changed. Electrostatic interactions appear not to be the only driving force regulating the interactions between NPs, proteins and cells since the specific recognition also play a fundamental role. However, the biological identity of LDH-NPs does not affect the interactions with cells that shows negligible cytotoxicity and high internalization levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Modelling the Transport of Nanoparticles under Blood Flow using an Agent-based Approach.

PubMed

Fullstone, Gavin; Wood, Jonathan; Holcombe, Mike; Battaglia, Giuseppe

2015-06-10

Blood-mediated nanoparticle delivery is a new and growing field in the development of therapeutics and diagnostics. Nanoparticle properties such as size, shape and surface chemistry can be controlled to improve their performance in biological systems. This enables modulation of immune system interactions, blood clearance profile and interaction with target cells, thereby aiding effective delivery of cargo within cells or tissues. Their ability to target and enter tissues from the blood is highly dependent on their behaviour under blood flow. Here we have produced an agent-based model of nanoparticle behaviour under blood flow in capillaries. We demonstrate that red blood cells are highly important for effective nanoparticle distribution within capillaries. Furthermore, we use this model to demonstrate how nanoparticle size can selectively target tumour tissue over normal tissue. We demonstrate that the polydispersity of nanoparticle populations is an important consideration in achieving optimal specificity and to avoid off-target effects. In future this model could be used for informing new nanoparticle design and to predict general and specific uptake properties under blood flow.

Type I Collagen and Collagen Mimetics as Angiogenesis Promoting Superpolymers

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

Twardowski, T.; Fertala, A.; Orgel, J.P.R.O.

Angiogenesis, the development of blood vessels from the pre-existing vasculature, is a key component of embryogenesis and tissue regeneration. Angiogenesis also drives pathologies such as tumor growth and metastasis, and hemangioma development in newborns. On the other hand, promotion of angiogenesis is needed in tissues with vascular insufficiencies, and in bioengineering, to endow tissue substitutes with appropriate microvasculatures. Therefore, much research has focused on defining mechanisms of angiogenesis, and identifying pro- and anti-angiogenic molecules. Type I collagen, the most abundant protein in humans, potently stimulates angiogenesis in vitro and in vivo. Crucial to its angiogenic activity appears to be ligationmore » and possibly clustering of endothelial cell (EC) surface {alpha}1{beta}1/{alpha}2{beta}1 integrin receptors by the GFPGER502-507 sequence of the collagen fibril. However, additional aspects of collagen structure and function that may modulate its angiogenic properties are discussed. Moreover, type I collagen and fibrin, another angiogenic polymer, share several structural features. These observations suggest strategies for creating 'angiogenic superpolymers', including: modifying type I collagen to influence its biological half-life, immunogenicity, and integrin binding capacity; genetically engineering fibrillar collagens to include additional integrin binding sites or angiogenic determinants, and remove unnecessary or deleterious sequences without compromising fibril integrity; and exploring the suitability of poly(ortho ester), PEG-lysine copolymer, tubulin, and cholesteric cuticle as collagen mimetics, and suggesting means of modifying them to display ideal angiogenic properties. The collagenous and collagen mimetic angiogenic superpolymers described here may someday prove useful for many applications in tissue engineering and human medicine.« less

Recovering a MOND-like acceleration law in mimetic gravity

NASA Astrophysics Data System (ADS)

Vagnozzi, Sunny

2017-09-01

We reconsider the recently proposed mimetic gravity, focusing in particular on whether the theory is able to reproduce the inferred flat rotation curves of galaxies. We extend the theory by adding a non-minimal coupling between matter and mimetic field. Such coupling leads to the appearance of an extra force which renders the motion of test particles non-geodesic. By studying the weak field limit of the resulting equations of motion, we demonstrate that in the Newtonian limit the acceleration law induced by the non-minimal coupling reduces to a modified Newtonian dynamics (MOND)-like one. In this way, it is possible to reproduce the successes of MOND, namely the explanation for the flat galactic rotation curves and the Tully-Fisher relation, within the framework of mimetic gravity, without the need for particle dark matter. The scale-dependence of the recovered acceleration scale opens up the possibility of addressing the missing mass problem not only on galactic but also on cluster scales: we defer a full study of this issue, together with a complete analysis of fits to spiral galaxy rotation curves, to an upcoming companion paper.

PVP and PEG doped CuO nanoparticles are more biologically active: Antibacterial, antioxidant, antidiabetic and cytotoxic perspective.

PubMed

Javed, Rabia; Ahmed, Madiha; Haq, Ihsan Ul; Nisa, Sobia; Zia, Muhammad

2017-10-01

Search for biologically active nanoparticles is prerequisite for biomedical applications. CuO nanoparticles synthesized by co-precipitation method are capped by polyethylene-glycol (PEG) and polyvinyl-pyrrolidone (PVP) on the surface by simple adsorption. Physical and chemical properties carried out by SEM, XRD and FTIR confirm nanometer in size and efficient capping of PVP and PEG on CuO NPs. Biological assays reveal higher activities of CuO-PEG and CuO-PVP as compared to the uncapped CuO nanoparticles. CuO-PEG shows better antitumor activity against Streptomyces as compared with CuO-PVP and CuO NPs. Both the capped NPs are significantly active for α-amylase inhibition assay. CuO-PVP demonstrates significantly better activity against bacterial strains followed by CuO-PEG and uncapped CuO. PVP coated CuO NPs also shows strong DPPH based free radical scavenging activity, total reducing power potential, total antioxidative potential and also carries flavonoid and phenolics properties determines to querecetin and gallic acid equivalence, respectively. It can be concluded that PVP and PEG capped CuO NPs are more capable to be used in biomedical applications as drug and diagnostic carrier molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Prey from the eyes of predators: Color discriminability of aposematic and mimetic butterflies from an avian visual perspective.

PubMed

Su, Shiyu; Lim, Matthew; Kunte, Krushnamegh

2015-11-01

Predation exerts strong selection on mimetic butterfly wing color patterns, which also serve other functions such as sexual selection. Therefore, specific selection pressures may affect the sexes and signal components differentially. We tested three predictions about the evolution of mimetic resemblance by comparing wing coloration of aposematic butterflies and their Batesian mimics: (a) females gain greater mimetic advantage than males and therefore are better mimics, (b) due to intersexual genetic correlations, sexually monomorphic mimics are better mimics than female-limited mimics, and (c) mimetic resemblance is better on the dorsal wing surface that is visible to predators in flight. Using a physiological model of avian color vision, we quantified mimetic resemblance from predators' perspective, which showed that female butterflies were better mimics than males. Mimetic resemblance in female-limited mimics was comparable to that in sexually monomorphic mimics, suggesting that intersexual genetic correlations did not constrain adaptive response to selection for female-limited mimicry. Mimetic resemblance on the ventral wing surface was better than that on the dorsal wing surface, implying stronger natural and sexual selection on ventral and dorsal surfaces, respectively. These results suggest that mimetic resemblance in butterfly mimicry rings has evolved under various selective pressures acting in a sex- and wing surface-specific manner. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

SiC nanoparticles as potential carriers for biologically active substances

NASA Astrophysics Data System (ADS)

Guevara-Lora, Ibeth; Czosnek, Cezary; Smycz, Aleksandra; Janik, Jerzy F.; Kozik, Andrzej

2009-01-01

Silicon carbide SiC thanks to its many advantageous properties has found numerous applications in diverse areas of technology. In this regard, its nanosized forms often with novel properties have been the subject of intense research in recent years. The aim of this study was to investigate the binding of biologically active substances onto SiC nanopowders as a new approach to biomolecule immobilization in terms of their prospective applications in medicine or for biochemical detection. The SiC nanoparticles were prepared by a two-stage aerosol-assisted synthesis from neat hexamethyldisiloxane. The binding of several proteins (bovine serum albumin, high molecular weight kininogen, immunoglobulin G) on SiC particle surfaces was demonstrated at the levels of 1-2 nanograms per mg of SiC. These values were found to significantly increase after suitable chemical modifications of nanoparticle surfaces (by carbodiimide or 3-aminopropyltrietoxysilane treatment). The study of SiC biocompatibility showed a lack of cytotoxicity against macrophages-like cells below the concentration of 1 mg nanoparticles per mL. In summary, we demonstrated the successful immobilization of the selected substances on the SiC nanoparticles. These results including the cytotoxicity study make nano-SiC highly attractive for potential applications in medicine, biotechnology or molecular detection.

Photoluminescent ZnO Nanoparticles and Their Biological Applications

PubMed Central

Zhang, Zheng-Yong; Xiong, Huan-Ming

2015-01-01

During the past decades, numerous achievements concerning luminescent zinc oxide nanoparticles (ZnO NPs) have been reported due to their improved luminescence and good biocompatibility. The photoluminescence of ZnO NPs usually contains two parts, the exciton-related ultraviolet (UV) emission and the defect-related visible emission. With respect to the visible emission, many routes have been developed to synthesize and functionalize ZnO NPs for the applications in detecting metal ions and biomolecules, biological fluorescence imaging, nonlinear multiphoton imaging, and fluorescence lifetime imaging. As the biological applications of ZnO NPs develop rapidly, the toxicity of ZnO NPs has attracted more and more attention because ZnO can produce the reactive oxygen species (ROS) and release Zn2+ ions. Just as a coin has two sides, both the drug delivery and the antibacterial effects of ZnO NPs become attractive at the same time. Hence, in this review, we will focus on the progress in the synthetic methods, luminescent properties, and biological applications of ZnO NPs.

Polyvinylpyrrolidone and arsenic-induced changes in biological responses of model aquatic organisms exposed to iron-based nanoparticles

NASA Astrophysics Data System (ADS)

Llaneza, Verónica; Rodea-Palomares, Ismael; Zhou, Zuo; Rosal, Roberto; Fernández-Pina, Francisca; Bonzongo, Jean-Claude J.

2016-08-01

The efficiency of zero-valent iron particles used in the remediation of contaminated groundwater has, with the emergence of nanotechnology, stimulated interest on the use of nano-size particles to take advantage of high-specific surface area and reactivity characteristics of nanoparticles (NPs). Accordingly, engineered iron-NPs are among the most widely used nanomaterials for in situ remediation. However, while several ecotoxicity studies have been conducted to investigate the adverse impacts of these NPs on aquatic organisms, research on the implications of spent iron-based NPs is lacking. In this study, a comparative approach is used, in which the biological effects of three iron-based NPs (Fe3O4 and γ-Fe2O3 NPs with particle sizes ranging from 20 to 50 nm, and Fe0-NPs with an average particle size of 40 nm) on Raphidocelis subcapitata (formely known as Pseudokirchneriella subcapitata) and Daphnia magna were investigated using both as-prepared and pollutant-doped Fe-based NPs. For the latter, arsenic (As) was used as example sorbed pollutant. The results show that improved degree of NP dispersion by use of polyvinylpyrrolidone overlapped with both increased arsenic adsorption capacity and toxicity to the tested organisms. For R. subcapitata, Fe-oxide NPs were more toxic than Fe0-NPs, due primarily to differences in the degree of NPs aggregation and ability to produce reactive oxygen species. For the invertebrate D. magna, a similar trend of biological responses was observed, except that sorption of As to Fe0-NPs significantly increased the toxic response when compared to R. subcapitata. Overall, these findings point to the need for research on downstream implications of NP-pollutant complexes generated during water treatment by injection of NPs into aquatic systems.

Smac mimetics and type II interferon synergistically induce necroptosis in various cancer cell lines.

PubMed

Cekay, Michael John; Roesler, Stefanie; Frank, Tanja; Knuth, Anne-Kathrin; Eckhardt, Ines; Fulda, Simone

2017-12-01

Since cancer cells often evade apoptosis, induction of necroptosis as another mode of programmed cell death is considered a promising therapeutic alternative. Here, we identify a novel synergistic interaction of Smac mimetics that antagonize x-linked Inhibitor of Apoptosis (XIAP), cellular Inhibitor of Apoptosis (cIAP) 1 and 2 with interferon (IFN)γ to induce necroptosis in apoptosis-resistant cancer cells in which caspase activation is blocked. This synergism is confirmed by calculation of combination indices (CIs) and found in both solid and hematological cancer cell lines as well as for different Smac mimetics (i.e. BV6, Birinapant), pointing to a broader relevance. Importantly, individual genetic knockdown of key components of necroptosis signaling, i.e. receptor-interacting protein (RIP) 1, RIP3 or mixed lineage kinase domain-like pseudokinase (MLKL), significantly protects from BV6/IFNγ-induced cell death. Similarly, pharmacological inhibitors of RIP1 (necrostatin-1(Nec-1)), RIP3 (GSK'872) or MLKL (necrosulfonamide (NSA)) significantly reduce BV6/IFNγ-stimulated cell death. Of note, IFN-regulatory factor (IRF)1 is required for BV6/IFNγ-mediated necroptosis, as IRF1 silencing provides protection from cell death. By comparison, antibodies blocking tumor necrosis factor (TNF)α, TNF-related apoptosis-inducing ligand (TRAIL) or CD95 ligand fail to inhibit BV6/IFNγ-induced cell death, pointing to a mechanism independently of death receptor ligands. This is the first report showing that Smac mimetics synergize with IFNγ to trigger necroptosis in apoptosis-resistant cancer cells with important implications for Smac mimetic-based strategies for the treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementing biological logic gates using gold nanoparticles conjugated to fluorophores

NASA Astrophysics Data System (ADS)

Barnoy, Eran A.; Popovtzer, Rachela; Fixler, Dror

2018-02-01

We describe recent research in which we explored biologically relevant logic gates using gold nanoparticles (GNPs) conjugated to fluorophores and tracing the results remotely by time-domain fluorescence lifetime imaging microscopy (FLIM). GNPs have a well-known effect on nearby fluorophores in terms of their fluorescence intensity (FI - increase or decrease) as well as fluorescence lifetime (FLT). We have designed a few bio-switch systems in which the FLIMdetected fluorescence varies after biologically relevant stimulation. Some of our tools include fluorescein diacetate (FDA) which can be activated by either esterases or pH, peptide chains cleavable by caspase 3, and the polymer polyacrylic acid which varies in size based on surrounding pH. After conjugating GNPs to chosen fluorophores, we have successfully demonstrated the logic gates of NOT, AND, OR, NAND, NOR, and XOR by imaging different stages of activation. These logic gates have been demonstrated both in solutions as well as within cultured cells, thereby possibly opening the door for nanoparticulate in vivo smart detection. While these initial probes are mainly tools for intelligent detection systems, they lay the foundation for logic gates functioning in conjunction so as to lead to a form of in vivo biological computing, where the system would be able to release proper treatment options in specific situations without external influence.

Modular protein switches derived from antibody mimetic proteins.

PubMed

Nicholes, N; Date, A; Beaujean, P; Hauk, P; Kanwar, M; Ostermeier, M

2016-02-01

Protein switches have potential applications as biosensors and selective protein therapeutics. Protein switches built by fusion of proteins with the prerequisite input and output functions are currently developed using an ad hoc process. A modular switch platform in which existing switches could be readily adapted to respond to any ligand would be advantageous. We investigated the feasibility of a modular protein switch platform based on fusions of the enzyme TEM-1 β-lactamase (BLA) with two different antibody mimetic proteins: designed ankyrin repeat proteins (DARPins) and monobodies. We created libraries of random insertions of the gene encoding BLA into genes encoding a DARPin or a monobody designed to bind maltose-binding protein (MBP). From these libraries, we used a genetic selection system for β-lactamase activity to identify genes that conferred MBP-dependent ampicillin resistance to Escherichia coli. Some of these selected genes encoded switch proteins whose enzymatic activity increased up to 14-fold in the presence of MBP. We next introduced mutations into the antibody mimetic domain of these switches that were known to cause binding to different ligands. To different degrees, introduction of the mutations resulted in switches with the desired specificity, illustrating the potential modularity of these platforms. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles

PubMed Central

MAGAYE, RUTH; ZHAO, JINSHUN; BOWMAN, LINDA; DING, MIN

2012-01-01

The nanotechnology industry has matured and expanded at a rapid pace in the last decade, leading to the research and development of nanomaterials with enormous potential. The largest source of these nanomaterials is the transitional metals. It has been revealed that numerous properties of these nano-sized elements are not present in their bulk states. The nano size of these particles means they are easily transported into biological systems, thus, raising the question of their effects on the susceptible systems. Although advances have been made and insights have been gained on the effect of transitional metals on susceptible biological systems, there still is much ground to be covered, particularly with respect to our knowledge on the genotoxic and carcinogenic effects. Therefore, this review intends to summarize the current knowledge on the genotoxic and carcinogenic potential of cobalt-, nickel- and copper-based nanoparticles indicated in in vitro and in vivo mammalian studies. In the present review, we briefly state the sources, use and exposure routes of these nanoparticles and summarize the current literature findings on their in vivo and in vitro genotoxic and carcinogenic effects. Due to the increasing evidence of their role in carcinogenicity, we have also included studies that have reported epigenetic factors, such as abnormal apoptosis, enhanced oxidative stress and pro-inflammatory effects involving these nanoparticles. PMID:23170105

Dye surface coating enables visible light activation of TiO2 nanoparticles leading to degradation of neighboring biological structures.

PubMed

Blatnik, Jay; Luebke, Lanette; Simonet, Stephanie; Nelson, Megan; Price, Race; Leek, Rachael; Zeng, Leyong; Wu, Aiguo; Brown, Eric

2012-02-01

Biologically and chemically modified nanoparticles are gaining much attention as a new tool in cancer detection and treatment. Herein, we demonstrate that an alizarin red S (ARS) dye coating on TiO2 nanoparticles enables visible light activation of the nanoparticles leading to degradation of neighboring biological structures through localized production of reactive oxygen species. Successful coating of nanoparticles with dye is demonstrated through sedimentation, spectrophotometry, and gel electrophoresis techniques. Using gel electrophoresis, we demonstrate that visible light activation of dye-TiO2 nanoparticles leads to degradation of plasmid DNA in vitro. Alterations in integrity and distribution of nuclear membrane associated proteins were detected via fluorescence confocal microscopy in HeLa cells exposed to perinuclear localized ARS-TiO2 nanoparticles that were photoactivated with visible light. This study expands upon previous studies that indicated dye coatings on TiO2 nanoparticles can serve to enhance imaging, by clearly showing that dye coatings on TiO2 nanoparticles can also enhance the photoreactivity of TiO2 nanoparticles by allowing visible light activation. The findings of our study suggest a therapeutic application of dye-coated TiO2 nanoparticles in cancer research; however, at the same time they may reveal limitations on the use of dye assisted visualization of TiO2 nanoparticles in live-cell imaging.

Luminescence of colloidal ZnO nanoparticles synthesized in alcohols and biological application of ZnO passivated by MgO

NASA Astrophysics Data System (ADS)

Sikora, Bożena; Fronc, Krzysztof; Kamińska, Izabela; Koper, Kamil; Stępień, Piotr; Elbaum, Danek

2013-05-01

This report presents the results of spectroscopic measurements of colloidal ZnO nanoparticles synthesized in various alcohols. Luminescence of colloidal ZnO was monitored under different reaction conditions to elucidate the mechanism of the visible emission. We performed the process in different alcohols, temperatures and reaction times for two different reactants: water and NaOH. Based on the presented and previously published results it is apparent that the luminescence of the nanoparticles is influenced by several competing phenomena: the formation of new nucleation centers, the growth of the nanoparticles and surface passivation. Superimposed on the above effects is a size dependent luminescence alteration resulting from the quantum confinement. The study contributes to our understanding of the origin of ZnO nanoparticles’ green emission which is important in a rational design of fluorescent probes for nontoxic biological applications. The ZnO nanoparticles were coated with a magnesium oxide layer and introduced into a HeLa cancer cell.

Sidedness of interfacial arginine residues and anti-atherogenicity of apolipoprotein A-I mimetic peptides

PubMed Central

Nayyar, Gaurav; Mishra, Vinod K.; Handattu, Shaila P.; Palgunachari, Mayakonda N.; Shin, Ronald; McPherson, David T.; Deivanayagam, Champion C. S.; Garber, David W.; Segrest, Jere P.; Anantharamaiah, G. M.

2012-01-01

To test the hypothesis that sidedness of interfacial arginine (Arg) in apoA-I mimetic peptides, similar to that observed in apoA-I (Bashtovyy, D. et al. 2011. Sequence conservation of apolipoprotein A-I affords novel insights into HDL structure-function. J. Lipid Res. 52: 435–450.), may be important for biological activity, we compared properties of 4F and analogs, [K4,15>R]4F and [K9,13>R]4F, with Lys>Arg substitutions on the right and left side, respectively, of the 4F amphipathic helix. Intraperitoneal administration of these peptides into female apoE null mice (n = 13 in each group) reduced en face lesions significantly compared with controls; 4F and [K4,15>R]4F were equally effective whereas [K9,13>R]4F was less effective. Turnover experiments indicated that [K4,15>R]4F reached the highest, whereas [K9,13>R]4F had the lowest, plasma peak levels with a similar half life as the [K4,15>R]4F analog. The half life of 4F was two times longer than the other two peptides. The order in their abilities to associate with HDL in human plasma, generation of apoA-I particles with pre-β mobility from isolated HDL, lipid associating ability, and sensitivity of lipid complexes to trypsin digestion was: 4F>[K4,15,>R]4F>[K9,13>R]4F. These studies support our hypothesis that the sidedness of interfacial Arg residues in the polar face of apoA-I mimetics results in differential biological properties. PMID:22377531

An In Ovo Model for Testing Insulin-mimetic Compounds.

PubMed

Haselgrübler, Renate; Stübl, Flora; Stadlbauer, Verena; Lanzerstorfer, Peter; Weghuber, Julian

2018-04-23

Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and β-cell failure. Various strategies, including the injection of insulin or the usage of insulin-sensitizing drugs, were pursued to treat T2DM or at least reduce the symptoms. In addition, the application of herbal compounds has attracted increasing attention. Thus, it is necessary to find efficient test systems to identify and characterize insulin-mimetic compounds. Here we developed a modified chick embryo model, which enables testing of synthetic compounds and herbal extracts with insulin-mimetic properties. Using a fluorescence microscopy-based primary screen, which quantifies the translocation of Glucose transporter 4 (Glut4) to the plasma membrane, we were able to identify compounds, mainly herbal extracts, which lead to an increase of intracellular glucose concentrations in adipocytes. However, the efficacy of these substances requires further verification in a living organism. Thus, we used an in-ovo approach to identify their blood glucose-reducing properties. The approval by an ethics committee is not needed since the use of chicken embryos during the first two-thirds of embryonic development is not considered an animal experiment. Here, the application of this model is described in detail.

Interaction of DNA bases with silver nanoparticles: assembly quantified through SPRS and SERS.

PubMed

Basu, Soumen; Jana, Subhra; Pande, Surojit; Pal, Tarasankar

2008-05-15

Colloidal silver nanoparticles were prepared by reducing silver nitrate with sodium borohydride. The synthesized silver particles show an intense surface plasmon band in the visible region. The work reported here describes the interaction between nanoscale silver particles and various DNA bases (adenine, guanine, cytosine, and thymine), which are used as molecular linkers because of their biological significance. In colloidal solutions, the color of silver nanoparticles may range from red to purple to orange to blue, depending on the degree of aggregation as well as the orientation of the individual particles within the aggregates. Transmission electron microscopy (TEM), X-ray diffraction (XRD), and absorption spectroscopy were used to characterize the assemblies. DNA base-induced differential silver nanoparticle aggregation was quantified from the peak separation (relates to color) of surface plasmon resonance spectroscopy (SPRS) and the signal intensity of surface-enhanced Raman scattering (SERS), which rationalize the extent of silver-nucleobase interactions.

Analytical detection and biological assay of antileukemic drug 5-fluorouracil using gold nanoparticles as probe.

PubMed

Selvaraj, Vaithilingam; Alagar, Muthukaruppan

2007-06-07

Gold nanoparticles are reported and evaluated as probes for the detection of anticancer drug 5-fluorouracil (5FU). The nature of binding between 5FU and gold nanoparticles via complexation is investigated using ultraviolet visible spectrophotometry, cyclic voltammetry, transmission electron microscopy, fluorescence and Fourier transform infrared (FTIR) spectroscopy. The bound antileukemic drug is fluorescent and the quenching property of gold nanoparticles could be exploited for biological investigations. The 5FU-colloidal gold complex (Au@5FU) is observed to have appreciable antibacterial and antifungal activity against Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Aspergillus fumigatus, and Aspergillus niger. The experimental studies suggest that gold nanoparticles have the potential to be used as effective carriers for anticancer drugs.

Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams

PubMed Central

Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

2014-01-01

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the

Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams.

PubMed

Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

2014-01-01

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects

Silk Fibroin-Based Nanoparticles for Drug Delivery

PubMed Central

Zhao, Zheng; Li, Yi; Xie, Mao-Bin

2015-01-01

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. PMID:25749470

Physiological adaptations following Roux-en-Y gastric bypass and the identification of targets for bariatric mimetic pharmacotherapy.

PubMed

Docherty, Neil G; Le Roux, Carel W

2015-12-01

The present opinion article provides an overview of the key improvements in metabolic and cardiovascular health following Roux-en-Y Gastric Bypass (RYGB). Some clinically important long-term complications of RYGB are also briefly described to contextualise the potential value of finding selective non-surgical means of replicating only the beneficial aspects of RYGB. Three biological responses linked to changes in gastrointestinal tract structure and function post-RYGB, that are implicated in the clinical efficacy of RYGB and that have actual or potential applications as non-surgical mimetic based approaches are addressed. These are (1) exaggerated post-prandial gut hormone responses; (2) local increases in undiluted bile in the gut lumen and augmented circulating bile acid and FGF19 concentrations and (3) compositional changes in the gut microbiota. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of neurotransmitters by a light scattering technique based on seed-mediated growth of gold nanoparticles

NASA Astrophysics Data System (ADS)

Shang, Li; Dong, Shaojun

2008-03-01

A simple light scattering detection method for neurotransmitters has been developed, based on the growth of gold nanoparticles. Neurotransmitters (dopamine, L-dopa, noradrenaline and adrenaline) can effectively function as active reducing agents for generating gold nanoparticles, which result in enhanced light scattering signals. The strong light scattering of gold nanoparticles then allows the quantitative detection of the neurotransmitters simply by using a common spectrofluorometer. In particular, Au-nanoparticle seeds were added to facilitate the growth of nanoparticles, which was found to enhance the sensing performance greatly. Using this light scattering technique based on the seed-mediated growth of gold nanoparticles, detection limits of 4.4 × 10-7 M, 3.5 × 10-7 M, 4.1 × 10-7 M, and 7.7 × 10-7 M were achieved for dopamine, L-dopa, noradrenaline and adrenaline, respectively. The present strategy can be extended to detect other biologically important molecules in a very fast, simple and sensitive way, and may have potential applications in a wide range of fields.

Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles.

PubMed

Dakwar, George R; Braeckmans, Kevin; Demeester, Joseph; Ceelen, Wim; De Smedt, Stefaan C; Remaut, Katrien

2015-11-04

Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.

The Photo-Physics of Polythiophene Nanoparticles for Biological Applications.

PubMed

Bargigia, Ilaria; Zucchetti, Elena; Srimath Kandada, Ajay Ram; Moreira, Miguel; Bossio, Caterina; Wong, Walter; Miranda, Paulo; Decuzzi, Paolo; Soci, Cesare; D'Andrea, Cosimo; Lanzani, Guglielmo

2018-05-01

In this work the photo-physics of poly(3-hexyltiophene) nanoparticles (NPs) is investigated in the context of their biological applications. The NPs made as colloidal suspensions in aqueous buffers present a distinct absorption band in the low energy region. Based on systematic analysis of absorption and transient absorption spectra taken under different pH conditions, this band is associated to charge transfer states generated by the polarization of loosely bound polymer chains and originated from complexes formed with electron withdrawing species. Importantly, the ground state depletion of these states upon photo-excitation is active even in the microsecond timescales, suggesting that they act as precursor states for long-living polarons which could be beneficial for cellular stimulation. Preliminary results of transient absorption microscopy of NPs internalized within the cells reveal the presence of long-living species, further substantiating their relevance in bio-interfaces. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biogenic silver nanoparticles based on trichoderma harzianum: synthesis, characterization, toxicity evaluation and biological activity

NASA Astrophysics Data System (ADS)

Guilger, Mariana; Pasquoto-Stigliani, Tatiane; Bilesky-Jose, Natália; Grillo, Renato; Abhilash, P. C.; Fraceto, Leonardo Fernandes; Lima, Renata De

2017-03-01

White mold is an agricultural disease caused by the fungus Sclerotinia sclerotiorum, which affects important crops. There are different ways of controlling this organism, but none provides inhibition of its resistance structures (sclerotia). Nanotechnology offers promising applications in agricultural area. Here, silver nanoparticles were biogenically synthesized using the fungus Trichoderma harzianum and characterized. Cytotoxicity and genotoxicity were evaluated, and the nanoparticles were initially tested against white mold sclerotia. Their effects on soybean were also investigated with no effects observed. The nanoparticles showed potential against S. sclerotiorum, inhibiting sclerotia germination and mycelial growth. Nanoparticle characterization data indicated spherical morphology, satisfactory polydispersity and size distribution. Cytotoxicity and genotoxicity assays showed that the nanoparticles caused both the effects, although, the most toxic concentrations were above those applied for white mold control. Given the potential of the nanoparticles against S. sclerotiorum, we conclude that this study presents a first step for a new alternative in white mold control.

Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles

PubMed Central

Polf, Jerimy C.; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata; Gillin, Michael

2011-01-01

The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%–20% for those cells containing internalized gold nanoparticles. PMID:21915155

Enhancing endosomal escape for nanoparticle mediated siRNA delivery

NASA Astrophysics Data System (ADS)

Ma, Da

2014-05-01

Gene therapy with siRNA is a promising biotechnology to treat cancer and other diseases. To realize siRNA-based gene therapy, a safe and efficient delivery method is essential. Nanoparticle mediated siRNA delivery is of great importance to overcome biological barriers for systemic delivery in vivo. Based on recent discoveries, endosomal escape is a critical biological barrier to be overcome for siRNA delivery. This feature article focuses on endosomal escape strategies used for nanoparticle mediated siRNA delivery, including cationic polymers, pH sensitive polymers, calcium phosphate, and cell penetrating peptides. Work has been done to develop different endosomal escape strategies based on nanoparticle types, administration routes, and target organ/cell types. Also, enhancement of endosomal escape has been considered along with other aspects of siRNA delivery to ensure target specific accumulation, high cell uptake, and low toxicity. By enhancing endosomal escape and overcoming other biological barriers, great progress has been achieved in nanoparticle mediated siRNA delivery.

The arbitrary order mixed mimetic finite difference method for the diffusion equation

DOE PAGES

Gyrya, Vitaliy; Lipnikov, Konstantin; Manzini, Gianmarco

2016-05-01

Here, we propose an arbitrary-order accurate mimetic finite difference (MFD) method for the approximation of diffusion problems in mixed form on unstructured polygonal and polyhedral meshes. As usual in the mimetic numerical technology, the method satisfies local consistency and stability conditions, which determines the accuracy and the well-posedness of the resulting approximation. The method also requires the definition of a high-order discrete divergence operator that is the discrete analog of the divergence operator and is acting on the degrees of freedom. The new family of mimetic methods is proved theoretically to be convergent and optimal error estimates for flux andmore » scalar variable are derived from the convergence analysis. A numerical experiment confirms the high-order accuracy of the method in solving diffusion problems with variable diffusion tensor. It is worth mentioning that the approximation of the scalar variable presents a superconvergence effect.« less

Room temperature preparation of fluorescent starch nanoparticles from starch-dopamine conjugates and their biological applications.

PubMed

Shi, Yingge; Xu, Dazhuang; Liu, Meiying; Fu, Lihua; Wan, Qing; Mao, Liucheng; Dai, Yanfeng; Wen, Yuanqing; Zhang, Xiaoyong; Wei, Yen

2018-01-01

Fluorescent organic nanoparticles (FONs) have been regarded as the promising candidates for biomedical applications owing to their well adjustment of chemical structure and optical properties and good biological properties. However, the preparation of FONs from the natural derived polymers has been rarely reported thus far. In current work, we reported a novel strategy for preparation of FONs based on the self-polymerization of starch-dopamine conjugates and polyethyleneimine in rather mild experimental conditions, including air atmosphere, aqueous solution, absent catalysts and at room temperature. The morphology, chemical structure and optical properties of the resultant starch-based FONs were investigated by different characterization techniques. Biological evaluation results demonstrated that these starch-based FONs possess good biocompatibility and fluorescent imaging performance. More importantly, the novel strategy might also be extended for the preparation of many other carbohydrate polymers based FONs with different structure and functions. Therefore, this work opens a new avenue for the preparation and biomedical applications of luminescent carbohydrate polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Allometric Growth of the Mimetic Ephippid Reef Fishes Chaetodipterus faber and Platax orbicularis.

PubMed

Barros, Breno; Sakai, Yoichi; Pereira, Pedro H C; Gasset, Eric; Buchet, Vincent; Maamaatuaiahutapu, Moana; Ready, Jonathan S; Oliveira, Yrlan; Giarrizzo, Tommaso; Vallinoto, Marcelo

2015-01-01

Mimesis is a relatively widespread phenomenon among reef fish, but the ontogenetic processes relevant for mimetic associations in fish are still poorly understood. In the present study, the allometric growth of two allopatric leaf-mimetic species of ephippid fishes, Chaetodipterus faber from the Atlantic and Platax orbicularis from the Indo-Pacific, was analyzed using ten morphological variables. The development of fins was considered owing to the importance of these structures for mimetic behaviors during early life stages. Despite the anatomical and behavioral similarities in both juvenile and adult stages, C. faber and P. orbicularis showed distinct patterns of growth. The overall shape of C. faber transforms from a rounded-shape in mimetic juveniles to a lengthened profile in adults, while in P. orbicularis, juveniles present an oblong profile including dorsal and anal fins, with relative fin size diminishing while the overall profile grows rounder in adults. Although the two species are closely-related, the present results suggest that growth patterns in C. faber and P. orbicularis are different, and are probably independent events in ephippids that have resulted from similar selective processes.

A Simple Assay for Ultrasensitive Colorimetric Detection of Ag⁺ at Picomolar Levels Using Platinum Nanoparticles.

PubMed

Wang, Yi-Wei; Wang, Meili; Wang, Lixing; Xu, Hui; Tang, Shurong; Yang, Huang-Hao; Zhang, Lan; Song, Hongbo

2017-11-02

In this work, uniformly-dispersed platinum nanoparticles (PtNPs) were synthesized by a simple chemical reduction method, in which citric acid and sodium borohydride acted as a stabilizer and reducer, respectively. An ultrasensitive colorimetric sensor for the facile and rapid detection of Ag⁺ ions was constructed based on the peroxidase mimetic activities of the obtained PtNPs, which can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H₂O₂ to produce colored products. The introduced Ag⁺ would be reduced to Ag⁰ by the capped citric acid, and the deposition of Ag⁰ on the PtNPs surface, can effectively inhibit the peroxidase-mimetic activity of PtNPs. Through measuring the maximum absorption signal of oxidized TMB at 652 nm, ultra-low detection limits (7.8 pM) of Ag⁺ can be reached. In addition to such high sensitivity, the colorimetric assay also displays excellent selectivity for other ions of interest and shows great potential for the detection of Ag⁺ in real water samples.

Green synthesized nickel nanoparticles for targeted detection and killing of S. typhimurium.

PubMed

Jeyaraj Pandian, Chitra; Palanivel, Rameshthangam; Balasundaram, Usha

2017-09-01

Simple and sensitive colorimetric immunosensor based on peroxidase mimetic activity and photothermal effect of nickel oxide nanoparticle (NiOGs) has been developed to detect and kill food borne pathogen Salmonella typhimurium. NiOGs showed superior peroxidase mimetic activity for oxidation of peroxidase substrate 3, 3', 5, 5'-tetramethylbenzidine (TMB). Oxidation of TMB by NiOGs followed Michaelis-Menten kinetics with K m and V max values of 0.25mM and 2.64×10 -8 M/s respectively. NiOGs was coated with citric acid (CA-NiOGs) followed by conjugation with antibody (anti-S. typhimurium) (Ab-CA-NiOGs) that effectively captured S. typhimurium. Colorimetric detection of S. typhimurium by Ab-CA-NiOGs showed a linear relationship between pathogen concentration (1×10 1 to 1×10 6 cfu/mL) and color signal (652nm) with limit of detection (LOD) of 10cfu/mL. The proposed method showed no cross reactivity against other pathogens. Recovery of S. typhimurium in milk and juice samples was found to be 95 to 100% and 92 to 99% respectively. NiOGs exposed to laser irradiation showed dose dependent increase in temperature and singlet oxygen within 5min. Bacteria bound to Ab-CA-NiOGs after laser irradiation, induced membrane damage and reduced bacterial viability to 6%. The bifunctional peroxidase-mimetic activity and photothermal effect of NiOGs can be exploited in selective sensing and killing of target pathogens respectively in food products. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydrogel nanoparticle based immunoassay

DOEpatents

Liotta, Lance A; Luchini, Alessandra; Petricoin, Emanuel F; Espina, Virginia

2015-04-21

An immunoassay device incorporating porous polymeric capture nanoparticles within either the sample collection vessel or pre-impregnated into a porous substratum within fluid flow path of the analytical device is presented. This incorporation of capture particles within the immunoassay device improves sensitivity while removing the requirement for pre-processing of samples prior to loading the immunoassay device. A preferred embodiment is coreshell bait containing capture nanoparticles which perform three functions in one step, in solution: a) molecular size sieving, b) target analyte sequestration and concentration, and c) protection from degradation. The polymeric matrix of the capture particles may be made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. This device is useful for point of care diagnostic assays for biomedical applications and as field deployable assays for environmental, pathogen and chemical or biological threat identification.

Effect of chemically and biologically synthesized Ag nanoparticles on the algae growth inhibition

NASA Astrophysics Data System (ADS)

Anna, Mražiková; Oksana, Velgosová; Jana, Kavuličová

2017-12-01

Over the past few years green methods for preparation of silver nanoparticles has become necessary due to its friendly influence on ecosystem. In the present work antimicrobial properties of biologically synthesized silver nanoparticles (Bio-AgNPs) using green algae extract and chemically synthesized silver nanoparticles (Chem-AgNPs) using sodium citrate against algae Parachlorella kessleri is investigated. Both used Bio-AgNPs and Chem-AgNPs exhibit long-term stability as demonstrated by UV-vis spectroscopy measurements. The results revealed stronger toxic effects of Bio-AgNPs on agar plates what was confirmed clear inhibition zone around wells impregnated with Bio-AgNPs. On the other hand Bio-AgNPs were confirmed to be less toxic in aquatic environments for the growths of green algae P. kessleri comparing to Chem-AgNPs.

Designer nanoparticle: nanobiotechnology tool for cell biology

NASA Astrophysics Data System (ADS)

Thimiri Govinda Raj, Deepak B.; Khan, Niamat Ali

2016-09-01

This article discusses the use of nanotechnology for subcellular compartment isolation and its application towards subcellular omics. This technology review significantly contributes to our understanding on use of nanotechnology for subcellular systems biology. Here we elaborate nanobiotechnology approach of using superparamagnetic nanoparticles (SPMNPs) optimized with different surface coatings for subcellular organelle isolation. Using pulse-chase approach, we review that SPMNPs interacted differently with the cell depending on its surface functionalization. The article focuses on the use of functionalized-SPMNPs as a nanobiotechnology tool to isolate high quality (both purity and yield) plasma membranes and endosomes or lysosomes. Such nanobiotechnology tool can be applied in generating subcellular compartment inventories. As a future perspective, this strategy could be applied in areas such as immunology, cancer and stem cell research.

Designer nanoparticle: nanobiotechnology tool for cell biology.

PubMed

Thimiri Govinda Raj, Deepak B; Khan, Niamat Ali

2016-01-01

This article discusses the use of nanotechnology for subcellular compartment isolation and its application towards subcellular omics. This technology review significantly contributes to our understanding on use of nanotechnology for subcellular systems biology. Here we elaborate nanobiotechnology approach of using superparamagnetic nanoparticles (SPMNPs) optimized with different surface coatings for subcellular organelle isolation. Using pulse-chase approach, we review that SPMNPs interacted differently with the cell depending on its surface functionalization. The article focuses on the use of functionalized-SPMNPs as a nanobiotechnology tool to isolate high quality (both purity and yield) plasma membranes and endosomes or lysosomes. Such nanobiotechnology tool can be applied in generating subcellular compartment inventories. As a future perspective, this strategy could be applied in areas such as immunology, cancer and stem cell research.

Nanoparticle-based strategy for personalized B-cell lymphoma therapy

PubMed Central

Martucci, Nicola M; Migliaccio, Nunzia; Ruggiero, Immacolata; Albano, Francesco; Calì, Gaetano; Romano, Simona; Terracciano, Monica; Rea, Ilaria; Arcari, Paolo; Lamberti, Annalisa

2016-01-01

B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas. PMID:27895482

Characterization of Nanoparticle Aggregation in Biologically Relevant Fluids

NASA Astrophysics Data System (ADS)

McEnnis, Kathleen; Lahann, Joerg

Nanoparticles (NPs) are often studied as drug delivery vehicles, but little is known about their behavior in blood once injected into animal models. If the NPs aggregate in blood, they will be shunted to the liver or spleen instead of reaching the intended target. The use of animals for these experiments is costly and raises ethical questions. Typically dynamic light scattering (DLS) is used to analyze aggregation behavior, but DLS cannot be used because the components of blood also scatter light. As an alternative, a method of analyzing NPs in biologically relevant fluids such as blood plasma has been developed using nanoparticle tracking analysis (NTA) with fluorescent filters. In this work, NTA was used to analyze the aggregation behavior of fluorescent polystyrene NPs with different surface modifications in blood plasma. It was expected that different surface chemistries on the particles will change the aggregation behavior. The effect of the surface modifications was investigated by quantifying the percentage of NPs in aggregates after addition to blood plasma. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems, specifically aggregation, can be addressed before investing in in vivo studies.

Red Fluorescent Carbon Nanoparticle-Based Cell Imaging Probe.

PubMed

Ali, Haydar; Bhunia, Susanta Kumar; Dalal, Chumki; Jana, Nikhil R

2016-04-13

Fluorescent carbon nanoparticle-based probes with tunable visible emission are biocompatible, environment friendly and most suitable for various biomedical applications. However, synthesis of red fluorescent carbon nanoparticles and their transformation into functional nanoparticles are very challenging. Here we report red fluorescent carbon nanoparticle-based nanobioconjugates of <25 nm hydrodynamic size and their application as fluorescent cell labels. Hydrophobic carbon nanoparticles are synthesized via high temperature colloid-chemical approach and transformed into water-soluble functional nanoparticles via coating with amphiphilic polymer followed by covalent linking with desired biomolecules. Following this approach, carbon nanoparticles are functionalized with polyethylene glycol, primary amine, glucose, arginine, histidine, biotin and folic acid. These functional nanoparticles can be excited with blue/green light (i.e., 400-550 nm) to capture their emission spanning from 550 to 750 nm. Arginine and folic acid functionalized nanoparticles have been demonstrated as fluorescent cell labels where blue and green excitation has been used for imaging of labeled cells. The presented method can be extended for the development of carbon nanoparticle-based other bioimaging probes.

Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles.

PubMed

Qasim, Muhammad; Udomluck, Nopphadol; Chang, Jihyun; Park, Hansoo; Kim, Kyobum

2018-01-01

In this study, we analyzed the antimicrobial activities of poly- N -isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH 2 -based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO 3 using NaBH 4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus ) bacteria depending on the nanoparticle size and amount of AgNO 3 used during fabrication.

Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles

PubMed Central

Qasim, Muhammad; Udomluck, Nopphadol; Chang, Jihyun; Park, Hansoo; Kim, Kyobum

2018-01-01

In this study, we analyzed the antimicrobial activities of poly-N-isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH2-based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO3 using NaBH4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria depending on the nanoparticle size and amount of AgNO3 used during fabrication. PMID:29379284

Chemoelectronic circuits based on metal nanoparticles

NASA Astrophysics Data System (ADS)

Yan, Yong; Warren, Scott C.; Fuller, Patrick; Grzybowski, Bartosz A.

2016-07-01

To develop electronic devices with novel functionalities and applications, various non-silicon-based materials are currently being explored. Nanoparticles have unique characteristics due to their small size, which can impart functions that are distinct from those of their bulk counterparts. The use of semiconductor nanoparticles has already led to improvements in the efficiency of solar cells, the processability of transistors and the sensitivity of photodetectors, and the optical and catalytic properties of metal nanoparticles have led to similar advances in plasmonics and energy conversion. However, metals screen electric fields and this has, so far, prevented their use in the design of all-metal nanoparticle circuitry. Here, we show that simple electronic circuits can be made exclusively from metal nanoparticles functionalized with charged organic ligands. In these materials, electronic currents are controlled by the ionic gradients of mobile counterions surrounding the ‘jammed’ nanoparticles. The nanoparticle-based electronic elements of the circuitry can be interfaced with metal nanoparticles capable of sensing various environmental changes (humidity, gas, the presence of various cations), creating electronic devices in which metal nanoparticles sense, process and ultimately report chemical signals. Because the constituent nanoparticles combine electronic and chemical sensing functions, we term these systems ‘chemoelectronic’. The circuits have switching times comparable to those of polymer electronics, selectively transduce parts-per-trillion chemical changes into electrical signals, perform logic operations, consume little power (on the scale of microwatts), and are mechanically flexible. They are also ‘green’, in the sense that they comprise non-toxic nanoparticles cast at room temperature from alcohol solutions.

Chemoelectronic circuits based on metal nanoparticles.

PubMed

Yan, Yong; Warren, Scott C; Fuller, Patrick; Grzybowski, Bartosz A

2016-07-01

To develop electronic devices with novel functionalities and applications, various non-silicon-based materials are currently being explored. Nanoparticles have unique characteristics due to their small size, which can impart functions that are distinct from those of their bulk counterparts. The use of semiconductor nanoparticles has already led to improvements in the efficiency of solar cells, the processability of transistors and the sensitivity of photodetectors, and the optical and catalytic properties of metal nanoparticles have led to similar advances in plasmonics and energy conversion. However, metals screen electric fields and this has, so far, prevented their use in the design of all-metal nanoparticle circuitry. Here, we show that simple electronic circuits can be made exclusively from metal nanoparticles functionalized with charged organic ligands. In these materials, electronic currents are controlled by the ionic gradients of mobile counterions surrounding the 'jammed' nanoparticles. The nanoparticle-based electronic elements of the circuitry can be interfaced with metal nanoparticles capable of sensing various environmental changes (humidity, gas, the presence of various cations), creating electronic devices in which metal nanoparticles sense, process and ultimately report chemical signals. Because the constituent nanoparticles combine electronic and chemical sensing functions, we term these systems 'chemoelectronic'. The circuits have switching times comparable to those of polymer electronics, selectively transduce parts-per-trillion chemical changes into electrical signals, perform logic operations, consume little power (on the scale of microwatts), and are mechanically flexible. They are also 'green', in the sense that they comprise non-toxic nanoparticles cast at room temperature from alcohol solutions.

A novel self-catalyzed photoATRP strategy for preparation of fluorescent hydroxyapatite nanoparticles and their biological imaging

NASA Astrophysics Data System (ADS)

Jiang, Ruming; Liu, Meiying; Huang, Hongye; Huang, Long; Huang, Qiang; Wen, Yuanqing; Cao, Qian-yong; Tian, Jianwen; Zhang, Xiaoyong; Wei, Yen

2018-03-01

Hydroxyapatite (HAp), as an important biomaterial for the regeneration and reconstruction of bone tissue, has attracted more and more attention of researchers and scientists due to its unique structure and compositions. However, the preparation of fluorescent HAp with controllable morphology has achieved only limited success. In this work, we reported a novel strategy to construct the water dispersible fluorescent HAp nanorods via the combination of ligand exchange and metal-free atom transfer radical polymerization (ATRP). The Br-containing fluorescent HAp nanorods with controllable size and morphology were first prepared through hydrothermal treatment. A multifunctional organic molecule (named as PTH-Br) with aggregation-induced emission feature was immobilized on the surface of hydrophobic HAp nanorods through ligand exchange reaction. The PTH-Br could be used as the initiator and catalyst for surface-initiated metal-free ATRP using poly(ethylene glycol) methacrylate as monomer to obtain hydrophilic fluorescent HAp polymer nanoparticles. This strategy successfully endowed HAp nanorods excellent fluorescence properties and favorable water dispersibility but well preserved their regular morphology. Biological assays demonstrated that the HAp-PTH-poly(PEGMA) nanoparticles exhibited good biocompatibility and efficient cell uptake performance. Taken together, we have developed a rather facile strategy based on the surface ligand exchange reaction and metal-free photoATRP to fabricate fluorescent HAp with controllable size and morphology, high water dispersibility and biological properties. These HAp-PTH-poly(PEGMA) nanoparticles should be novel and promising candidates for biomedical applications.

Comparative Allometric Growth of the Mimetic Ephippid Reef Fishes Chaetodipterus faber and Platax orbicularis

PubMed Central

Barros, Breno; Sakai, Yoichi; Pereira, Pedro H. C.; Gasset, Eric; Buchet, Vincent; Maamaatuaiahutapu, Moana; Ready, Jonathan S.; Oliveira, Yrlan; Giarrizzo, Tommaso; Vallinoto, Marcelo

2015-01-01

Mimesis is a relatively widespread phenomenon among reef fish, but the ontogenetic processes relevant for mimetic associations in fish are still poorly understood. In the present study, the allometric growth of two allopatric leaf-mimetic species of ephippid fishes, Chaetodipterus faber from the Atlantic and Platax orbicularis from the Indo-Pacific, was analyzed using ten morphological variables. The development of fins was considered owing to the importance of these structures for mimetic behaviors during early life stages. Despite the anatomical and behavioral similarities in both juvenile and adult stages, C. faber and P. orbicularis showed distinct patterns of growth. The overall shape of C. faber transforms from a rounded-shape in mimetic juveniles to a lengthened profile in adults, while in P. orbicularis, juveniles present an oblong profile including dorsal and anal fins, with relative fin size diminishing while the overall profile grows rounder in adults. Although the two species are closely-related, the present results suggest that growth patterns in C. faber and P. orbicularis are different, and are probably independent events in ephippids that have resulted from similar selective processes. PMID:26630347

Copper Nanoparticles: Synthesis and Biological Activity

NASA Astrophysics Data System (ADS)

Satyvaldiev, A. S.; Zhasnakunov, Z. K.; Omurzak, E.; Doolotkeldieva, T. D.; Bobusheva, S. T.; Orozmatova, G. T.; Kelgenbaeva, Z.

2018-01-01

By means of XRD and FESEM analysis, it is established that copper nanoparticles with sizes less than 10 nm are formed during the chemical reduction, which form aggregates mainly with spherical shape. Presence of gelatin during the chemical reduction of copper induced formation of smaller size distribution nanoparticles than that of nanoparticles synthesized without gelatin and it can be related to formation of protective layer. Synthesized Cu nano-powders have sufficiently high activity against the Erwinia amylovora bacterium, and the bacterial growth inhibition depends on the Cu nanoparticles concentration. At a concentration of 5 mg / ml of Cu nanoparticles, the exciter growth inhibition zone reaches a maximum value within 72 hours and the lysis zone is 20 mm, and at a concentration of 1 mg / ml this value is 16 mm, which also indicates the significant antibacterial activity of this sample.

Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits

PubMed Central

Busseuil, D; Shi, Y; Mecteau, M; Brand, G; Kernaleguen, A-E; Thorin, E; Latour, J-G; Rhéaume, E; Tardif, J-C

2008-01-01

Background and purpose: Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS. Experimental approach: Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Key results: Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness. Conclusions and implications: Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease. PMID:18414386

A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly

NASA Astrophysics Data System (ADS)

Li, Yong; Li, Wang; He, Kai-Yu; Li, Pei; Huang, Yan; Nie, Zhou; Yao, Shou-Zhuo

2016-04-01

In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation.In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular

Influence of SiO2 and graphene oxide nanoparticles on efficiency of biological removal process.

PubMed

Esmaeili-Faraj, Seyyed Hamid; Nasr Esfahany, Mohsen

2017-11-01

The effects of the presence of synthesized silica (SS) and exfoliated graphene oxide (EGO) on the removal of sulfide ion with activated sludge (AS) are experimentally investigated. The maximum removal efficiency of sulfide ion for AS without nanoparticles, and the samples with SS and EGO nanoparticles were 81%, 88% and 79%, respectively. Moreover, the maximum elimination capacity (EC max ) for the bioreactor with SS-nanoparticles is 7542 mg/L s, while the EC max of AS and EGO samples were 7075 and 6625 mg/L s, respectively. Two filamentous microbial strains as Gram-negative and Gram-positive bacteria are discerned that removed sulfide ion in the presence of nanoparticles. The measurement of mixture liquor volatile suspended solid that indicates the biomass growth rate during the test shows that the bioreactor containing SS-nanoparticles has more biomass content than the other samples. Our findings indicate that SS-nanoparticles with 0.1% wt. concentration in the bioreactor have no negative effects on the efficiency of the biological removal of sulfide and the presence of SS-nanoparticles even enhances the performance of the bioreactor. On the other side, a bioreactor with EGO nanosheets, as highly antibacterial nanoparticles, with 0.02% wt. concentration significantly influences the microbial growth and reduces sulfide removal efficiency.

Mixed Contaminants Removal Efficiency Using Bio-FeS Nanoparticles.

PubMed

Seo, Hyunhee; Roh, Yul

2018-02-01

Advances in nanotechnology has provided diverse industrial applications including an environmental remediation field. In particular, bio-nanotechnology gives extended eco-friendly remediation practice. Among diverse bio-nanoparticles synthesized by microorganisms, the iron based nanoparticles (NPs) are of great interest because of their availability, low cost and toxicity to human health and the environment. In this study, iron based nanoparticles were biologically synthesized and mineralogically identified. Also, the removal efficiency of mixed contaminants, high As(III)-low Cr(VI) and high As(V)-low Cr(VI), using these bio-nanoparticles were conducted. As a result, biologically synthesized NPs were identified as FeS complex and their catalytic capacity showed highly effective to immobilize more than 97% of mixed contaminants by adsorption/mineralization.

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

PubMed Central

Sykes, Edward A.; Dai, Qin; Sarsons, Christopher D.; Chen, Juan; Rocheleau, Jonathan V.; Hwang, David M.; Zheng, Gang; Cramb, David T.; Rinker, Kristina D.; Chan, Warren C. W.

2016-01-01

Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient’s disease state to achieve optimal diagnostic and therapeutic outcomes. PMID:26884153

Fluorescent nanoparticles based on AIE fluorogens for bioimaging.

PubMed

Yan, Lulin; Zhang, Yan; Xu, Bin; Tian, Wenjing

2016-02-07

Fluorescent nanoparticles (FNPs) have recently attracted increasing attention in the biomedical field because of their unique optical properties, easy fabrication and outstanding performance in imaging. Compared with conventional molecular probes including small organic dyes and fluorescent proteins, FNPs based on aggregation-induced emission (AIE) fluorogens have shown significant advantages in tunable emission and brightness, good biocompatibility, superb photo- and physical stability, potential biodegradability and facile surface functionalization. In this review, we summarize the latest advances in the development of fluorescent nanoparticles based on AIE fluorogens including polymer nanoparticles and silica nanoparticles over the past few years, and the various biomedical applications based on these fluorescent nanoparticles are also elaborated.

Minimalist Antibodies and Mimetics: An Update and Recent Applications.

PubMed

Bruce, Virginia J; Ta, Angeline N; McNaughton, Brian R

2016-10-17

The immune system utilizes antibodies to recognize foreign or disease-relevant receptors, initiating an immune response to destroy unwelcomed guests. Because researchers can evolve antibodies to bind virtually any target, it is perhaps unsurprising that these reagents, and their small-molecule conjugates, are used extensively in clinical and basic research environments. However, virtues of antibodies are countered by significant challenges. Foremost among these is the need for expression in mammalian cells (largely due to often necessary post-translational modifications). In response to these challenges, researchers have developed an array of minimalist antibodies and mimetics, which are smaller, more stable, simpler to express in Escherichia coli, and amendable to laboratory evolution and protein engineering. Here we describe these scaffolds and discuss recent applications of minimalist antibodies and mimetics. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dye-doped silica-based nanoparticles for bioapplications

NASA Astrophysics Data System (ADS)

Nhung Tran, Hong; Nghiem, Thi Ha Lien; Thuy Duong Vu, Thi; Tan Pham, Minh; Van Nguyen, Thi; Trang Tran, Thu; Chu, Viet Ha; Thuan Tong, Kim; Thuy Tran, Thanh; Le, Thi Thanh Xuan; Brochon, Jean-Claude; Quy Nguyen, Thi; Nhung Hoang, My; Nguyen Duong, Cao; Thuy Nguyen, Thi; Hoang, Anh Tuan; Hoa Nguyen, Phuong

2013-12-01

This paper presents our recent research results on synthesis and bioapplications of dye-doped silica-based nanoparticles. The dye-doped water soluble organically modified silicate (ORMOSIL) nanoparticles (NPs) with the size of 15-100 nm were synthesized by modified Stöber method from methyltriethoxysilane CH3Si(OCH3)3 precursor (MTEOS). Because thousands of fluorescent dye molecules are encapsulated in the silica-based matrix, the dye-doped nanoparticles are extremely bright and photostable. Their surfaces were modified with bovine serum albumin (BSA) and biocompatible chemical reagents. The highly intensive luminescent nanoparticles were combined with specific bacterial and breast cancer antigen antibodies. The antibody-conjugated nanoparticles can identify a variety of bacterium, such as Escherichia coli O157:H7, through antibody-antigen interaction and recognition. A highly sensitive breast cancer cell detection has been achieved with the anti-HER2 monoclonal antibody-nanoparticles complex. These results demonstrate the potential to apply these fluorescent nanoparticles in various biodetection systems.

Size-controlled green synthesis of silver nanoparticles mediated by gum ghatti (Anogeissus latifolia) and its biological activity

PubMed Central

2012-01-01

Background Gum ghatti is a proteinaceous edible, exudate tree gum of India and is also used in traditional medicine. A facile and ecofriendly green method has been developed for the synthesis of silver nanoparticles from silver nitrate using gum ghatti (Anogeissus latifolia) as a reducing and stabilizing agent. The influence of concentration of gum and reaction time on the synthesis of nanoparticles was studied. UV–visible spectroscopy, transmission electron microscopy and X-ray diffraction analytical techniques were used to characterize the synthesized nanoparticles. Results By optimizing the reaction conditions, we could achieve nearly monodispersed and size controlled spherical nanoparticles of around 5.7 ± 0.2 nm. A possible mechanism involved in the reduction and stabilization of nanoparticles has been investigated using Fourier transform infrared spectroscopy and Raman spectroscopy. Conclusions The synthesized silver nanoparticles had significant antibacterial action on both the Gram classes of bacteria. As the silver nanoparticles are encapsulated with functional group rich gum, they can be easily integrated for various biological applications. PMID:22571686

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment.

PubMed

Li, Ruixiang; He, Yuwei; Zhang, Shuya; Qin, Jing; Wang, Jianxin

2018-01-01

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2006-11-15

Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl beta cyclodextrin-insulin (HPbetaCD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HPbetaCD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HPbetaCD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immunosorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

Gold nanoparticle-based enhanced chemiluminescence immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food.

PubMed

Yang, Minghui; Kostov, Yordan; Bruck, Hugh A; Rasooly, Avraham

2009-08-15

Staphylococcal enterotoxins (SEs) are major cause of foodborne diseases, so sensitive detection (<1 ng/ml) methods are needed for SE detection in food. The surface area, geometric and physical properties of gold nanoparticles make them well-suited for enhancing interactions with biological molecules in assays. To take advantage of the properties of gold nanoparticles for immunodetection, we have developed a gold nanoparticle-based enhanced chemiluminescence (ECL) immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food. Anti-SEB primary antibodies were immobilized onto a gold nanoparticle surface through physical adsorption and then the antibody-gold nanoparticle mixture was immobilized onto a polycarbonate surface. SEB was detected by a "sandwich-type" ELISA assay on the polycarbonate surface with a secondary antibody and ECL detection. The signal from ECL was read using a point-of-care detector based on a cooled charge-coupled device (CCD) sensor or a plate reader. The system was used to test for SEB in buffer and various foods (mushrooms, tomatoes, and baby food meat). The limit of detection was found to be approximately 0.01 ng/mL, which is approximately 10 times more sensitive than traditional ELISA. The gold nanoparticles were relatively easy to use for antibody immobilization because of their physical adsorption mechanism; no other reagents were required for immobilization. The use of our simple and inexpensive detector combined with the gold nanoparticle-based ECL method described here is adaptable to simplify and increase sensitivity of any immunological assay and for point-of-care diagnostics.

Gold nanoparticle-based enhanced chemiluminescence immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food

PubMed Central

Yang, Minghui; Kostov, Yordan; Bruck, Hugh A.; Rasooly, Avraham

2010-01-01

Staphylococcal enterotoxins (SEs) are major cause of foodborne diseases, so sensitive detection (<1 ng/ml) methods are needed for SE detection in food. The surface area, geometric and physical properties of gold nanoparticles make them well-suited for enhancing interactions with biological molecules in assays. To take advantage of the properties of gold nanoparticles for immunodetection, we have developed a gold nanoparticle-based enhanced chemiluminescence (ECL) immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food. Anti-SEB primary antibodies were immobilized onto a gold nanoparticle surface through physical adsorption and then the antibody–gold nanoparticle mixture was immobilized onto a polycarbonate surface. SEB was detected by a “sandwich-type” ELISA assay on the polycarbonate surface with a secondary antibody and ECL detection. The signal from ECL was read using a point-of-care detector based on a cooled charge-coupled device (CCD) sensor or a plate reader. The system was used to test for SEB in buffer and various foods (mushrooms, tomatoes, and baby food meat). The limit of detection was found to be ~0.01 ng/mL, which is ~10 times more sensitive than traditional ELISA. The gold nanoparticles were relatively easy to use for antibody immobilization because of their physical adsorption mechanism; no other reagents were required for immobilization. The use of our simple and inexpensive detector combined with the gold nanoparticle-based ECL method described here is adaptable to simplify and increase sensitivity of any immunological assay and for point-of-care diagnostics. PMID:19540011

Techniques for Accurate Sizing of Gold Nanoparticles Using Dynamic Light Scattering with Particular Application to Chemical and Biological Sensing Based on Aggregate Formation.

PubMed

Zheng, Tianyu; Bott, Steven; Huo, Qun

2016-08-24

Gold nanoparticles (AuNPs) have found broad applications in chemical and biological sensing, catalysis, biomolecular imaging, in vitro diagnostics, cancer therapy, and many other areas. Dynamic light scattering (DLS) is an analytical tool used routinely for nanoparticle size measurement and analysis. Due to its relatively low cost and ease of operation in comparison to other more sophisticated techniques, DLS is the primary choice of instrumentation for analyzing the size and size distribution of nanoparticle suspensions. However, many DLS users are unfamiliar with the principles behind the DLS measurement and are unware of some of the intrinsic limitations as well as the unique capabilities of this technique. The lack of sufficient understanding of DLS often leads to inappropriate experimental design and misinterpretation of the data. In this study, we performed DLS analyses on a series of citrate-stabilized AuNPs with diameters ranging from 10 to 100 nm. Our study shows that the measured hydrodynamic diameters of the AuNPs can vary significantly with concentration and incident laser power. The scattered light intensity of the AuNPs has a nearly sixth order power law increase with diameter, and the enormous scattered light intensity of AuNPs with diameters around or exceeding 80 nm causes a substantial multiple scattering effect in conventional DLS instruments. The effect leads to significant errors in the reported average hydrodynamic diameter of the AuNPs when the measurements are analyzed in the conventional way, without accounting for the multiple scattering. We present here some useful methods to obtain the accurate hydrodynamic size of the AuNPs using DLS. We also demonstrate and explain an extremely powerful aspect of DLS-its exceptional sensitivity in detecting gold nanoparticle aggregate formation, and the use of this unique capability for chemical and biological sensing applications.

Inhibiting NANOG Enhances Efficacy of BH3 Mimetics | Center for Cancer Research

Cancer.gov

BCL-2 family proteins regulate cell fate. Some members promote cell survival while others induce programmed cell death. A third group, the BH3-only members, modulates the activities of the rest of the family. Some cancers, including those of the colon and rectum, express elevated levels of pro-survival BCL-2 members, which may protect cancer cells from chemotherapy. BH3 mimetics are novel therapies that target and inhibit these pro-survival family members. Two in particular, ABT-737 and ABT-199, have activity against multiple cancer types, though neither targets the protein MCL-1, which is related to the BCL-2 family and causes resistance to the BH3 mimetics. Recent studies have revealed that the embryonic regulator NANOG and the related gene NANOGP8 can indirectly regulate MCL-1 via the kinase AKT. Abid Mattoo, Ph.D., J. Milburn Jessup, M.D., and colleagues of CCR’s Laboratory of Experimental Carcinogenesis, hypothesized that combining NANOG or NANOGP8 inhibition with a BH3 mimetic would enhance the latter’s anticancer activity.

A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly.

PubMed

Li, Yong; Li, Wang; He, Kai-Yu; Li, Pei; Huang, Yan; Nie, Zhou; Yao, Shou-Zhuo

2016-04-28

In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation.

Preparation and antibacterial performance testing of Ag nanoparticles embedded biological materials

NASA Astrophysics Data System (ADS)

Li, Xiaoyun; Gao, Guanhui; Sun, Chengjun; Zhu, Yaoyao; Qu, Lingyun; Jiang, Fenghua; Ding, Haibing

2015-03-01

In this study, we developed an environmentally friendly chemistry strategy to synthesize Ag nanoparticles (Ag-NPs) embedded biological material, powdered mussel shell (PMS). With the PMS as scaffolds and surfactant, Ag nanoparticles of controllable size dispersed uniformly on it via liquid chemical reduction approach. Morphologies and characteristics of synthesized Ag-NPs/PMS hybrids were analyzed with TEM, SEM and XPS. Antibacterial properties were investigated with Gram-positive bacteria (Arthrobacter sulfureus (A. sulfureus) YACS14, Staphylococcus aureus (S. aureus)) and Gram-negative bacteria (Vibrio anguillarum (V. anguillarum) MVM425, Escherichia coli (E. coli)). The antimicrobial results illustrated that Ag-NPs/PMS composites have antibacterial effect on both sea water and fresh water bacteria with a better effect on sea water bacteria. The degree of antibacterial effect is directly related to the amount of Ag released from Ag-NPs/PMS.

BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models.

PubMed

Morii, Takeshi; Ohtsuka, Kouki; Ohnishi, Hiroaki; Mochizuki, Kazuo; Yoshiyama, Akira; Aoyagi, Takayuki; Hornicek, Francis J; Ichimura, Shoichi

2014-11-01

Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells. Chondrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak). In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcoma growth and improved survival in a mouse model. BH3 mimetics represent a novel treatment modality for chondrosarcoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

MPQ-cytometry: a magnetism-based method for quantification of nanoparticle-cell interactions

NASA Astrophysics Data System (ADS)

Shipunova, V. O.; Nikitin, M. P.; Nikitin, P. I.; Deyev, S. M.

2016-06-01

Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method called MPQ-cytometry is developed, which measures the integral non-linear response produced by magnetically labeled nanoparticles in a cell sample with an original magnetic particle quantification (MPQ) technique. MPQ-cytometry provides a sensitivity limit 0.33 ng of nanoparticles and is devoid of a background signal present in many label-based assays. Each measurement takes only a few seconds, and no complicated sample preparation or data processing is required. The capabilities of the method have been demonstrated by quantification of interactions of iron oxide nanoparticles with eukaryotic cells. The total amount of targeted nanoparticles that specifically recognized the HER2/neu oncomarker on the human cancer cell surface was successfully measured, the specificity of interaction permitting the detection of HER2/neu positive cells in a cell mixture. Moreover, it has been shown that MPQ-cytometry analysis of a HER2/neu-specific iron oxide nanoparticle interaction with six cell lines of different tissue origins quantitatively reflects the HER2/neu status of the cells. High correlation of MPQ-cytometry data with those obtained by three other commonly used in molecular and cell biology methods supports consideration of this method as a prospective alternative for both quantifying cell-bound nanoparticles and estimating the expression level of cell surface antigens. The proposed method does not require expensive sophisticated equipment or highly skilled personnel and it can be easily applied for rapid diagnostics, especially under field conditions.Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method

Smart nanoparticles as targeting platforms for HIV infections

NASA Astrophysics Data System (ADS)

Adhikary, Rishi Rajat; More, Prachi; Banerjee, Rinti

2015-04-01

While Human Immunodeficiency Virus (HIV) infections are reducing in incidence with the advent of Highly Active Anti-retroviral Therapy (HAART), there remain a number of challenges including the existence of reservoirs, drug resistance and anatomical barriers to antiretroviral therapy. To overcome these, smart nanoparticles with stimuli responsive release are proposed for delivery of anti-retroviral agents. The paper highlights the strategic similarities between the design of smart antiretroviral nanocarriers and those optimized for cancer chemotherapy. This includes the development of nanoparticles capable of passive and active targeting as well as those that are responsive to various internal and external triggers. For antiretroviral therapy, the relevant triggers for stimuli responsive release of drugs include semen, enzymes, endosomal escape, temperature and magnetic field. Deriving from the experience of cancer chemotherapy, additional potential triggers are light and ultrasound which remain hitherto unexplored in HIV therapy. In addition, the roles of nanomicrobicides (nanogels) and virus mimetic nanoparticles are discussed from the point of view of prevention of HIV transmission. The challenges associated with translation of smart nanoparticles for HIV infections to realize the Millennium Development Goal of combating HIV infections are discussed.

Smart nanoparticles as targeting platforms for HIV infections.

PubMed

Adhikary, Rishi Rajat; More, Prachi; Banerjee, Rinti

2015-05-07

While Human Immunodeficiency Virus (HIV) infections are reducing in incidence with the advent of Highly Active Anti-retroviral Therapy (HAART), there remain a number of challenges including the existence of reservoirs, drug resistance and anatomical barriers to antiretroviral therapy. To overcome these, smart nanoparticles with stimuli responsive release are proposed for delivery of anti-retroviral agents. The paper highlights the strategic similarities between the design of smart antiretroviral nanocarriers and those optimized for cancer chemotherapy. This includes the development of nanoparticles capable of passive and active targeting as well as those that are responsive to various internal and external triggers. For antiretroviral therapy, the relevant triggers for stimuli responsive release of drugs include semen, enzymes, endosomal escape, temperature and magnetic field. Deriving from the experience of cancer chemotherapy, additional potential triggers are light and ultrasound which remain hitherto unexplored in HIV therapy. In addition, the roles of nanomicrobicides (nanogels) and virus mimetic nanoparticles are discussed from the point of view of prevention of HIV transmission. The challenges associated with translation of smart nanoparticles for HIV infections to realize the Millennium Development Goal of combating HIV infections are discussed.

The method of radioactive tracer for measuring the amount of inorganic nanoparticles in biological samples

NASA Astrophysics Data System (ADS)

Buzulukov, Yu; Antsiferova, A.; Demin, V. A.; Demin, V. F.; Kashkarov, P.

2015-11-01

The method to measure the mass of inorganic nanoparticles in biological (or any other samples) using nanoparticles labeled with radioactive tracers is developed and applied to practice. The tracers are produced in original nanoparticles by radioactive activation of some of their atomic nuclei. The method of radioactive tracers demonstrates a sensitivity, specificity and accuracy equal or better than popular methods of optical and mass spectrometry, or electron microscopy and has some specific advantages. The method can be used for study of absorption, distribution, metabolism and excretion in living organism, as well as in ecological and fundamental research. It was used in practice to study absorption, distribution, metabolism and excretion of nanoparticles of Ag, Au, Se, ZnO, TiO2 as well as to study transportation of silver nanoparticles through the barriers of blood-brain, placenta and milk gland of rats. Brief descriptions of data obtained in experiments with application of this method included in the article. The method was certified in Russian Federation standard system GOST-R and recommended by the Russian Federation regulation authority ROSPOTREBNADZOR for measuring of toxicokinetic and organotropy parameters of nanoparticles.

Glyconanoparticles: types, synthesis and applications in glycoscience, biomedicine and material science.

PubMed

de la Fuente, Jesús M; Penadés, Soledad

2006-04-01

Nanoparticles are the subject of numerous papers and reports and are full of promises for electronic, optical, magnetic and biomedical applications. Although metallic nanoparticles have been functionalized with peptides, proteins and DNA during the last 20 years, carbohydrates have not been used with this purpose until 2001. Since the first synthesis of gold nanoparticles functionalized with carbohydrates (glyconanoparticles) was reported, the number of published articles has considerably increased. This article reviews progress in the development of nanoparticles functionalized with biological relevant oligosaccharides. The glyconanoparticles constitute a good bio-mimetic model of carbohydrate presentation at the cell surface, and maybe, excellent tools for Glycobiology, Biomedicine and Material Science investigations.

Standardization of Nanoparticle Characterization: Methods for Testing Properties, Stability, and Functionality of Edible Nanoparticles.

PubMed

McClements, Jake; McClements, David Julian

2016-06-10

There has been a rapid increase in the fabrication of various kinds of edible nanoparticles for oral delivery of bioactive agents, such as those constructed from proteins, carbohydrates, lipids, and/or minerals. It is currently difficult to compare the relative advantages and disadvantages of different kinds of nanoparticle-based delivery systems because researchers use different analytical instruments and protocols to characterize them. In this paper, we briefly review the various analytical methods available for characterizing the properties of edible nanoparticles, such as composition, morphology, size, charge, physical state, and stability. This information is then used to propose a number of standardized protocols for characterizing nanoparticle properties, for evaluating their stability to environmental stresses, and for predicting their biological fate. Implementation of these protocols would facilitate comparison of the performance of nanoparticles under standardized conditions, which would facilitate the rational selection of nanoparticle-based delivery systems for different applications in the food, health care, and pharmaceutical industries.

Gold nanoparticles synthesis and biological activity estimation in vitro and in vivo.

PubMed

Rieznichenko, L S; Dybkova, S M; Gruzina, T G; Ulberg, Z R; Todor, I N; Lukyanova, N Yu; Shpyleva, S I; Chekhun, V F

2012-01-01

The aim of the work was the synthesis of gold nanoparticles (GNP) of different sizes and the estimation of their biological activity in vitro and in vivo. Water dispersions of gold nanoparticles of different sizes have been synthesized by Davis method and characterized by laser-correlation spectroscopy and transmission electron microscopy methods. The GNP interaction with tumor cells has been visualized by confocal microscopy method. The enzyme activity was determined by standard biochemical methods. GNP distribution and content in organs and tissues have been determined via atomic-absorption spectrometry method; genotoxic influence has been estimated by "Comet-assay" method. The GNP size-dependent accumulation in cultured U937 tumor cells and their ability to modulate U937 cell membrane Na(+),K(+)-АТР-ase activity value has been revealed in vitro. Using in vivo model of Guerin carcinoma it has been shown that GNP possess high affinity to tumor cells. Our results indicate the perspectives of use of the synthesized GNP water dispersions for cancer diagnostics and treatment. It's necessary to take into account a size-dependent biosafety level of nanoparticles.

Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study

PubMed Central

Papageorgiou, Iraklis; Abberton, Thomas; Fuller, Martin; Tipper, Joanne L.; Fisher, John; Ingham, Eileen

2014-01-01

Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days of in vitro culture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue. PMID:28344233

Molecular Design, Structures, and Activity of Antimicrobial Peptide-Mimetic Polymers

PubMed Central

Takahashi, Haruko; Palermo, Edmund F.; Yasuhara, Kazuma; Caputo, Gregory A.

2014-01-01

There is an urgent need for new antibiotics which are effective against drug-resistant bacteria without contributing to resistance development. We have designed and developed antimicrobial copolymers with cationic amphiphilic structures based on the mimicry of naturally occurring antimicrobial peptides. These copolymers exhibit potent antimicrobial activity against a broad spectrum of bacteria including methicillin-resistant Staphylococcus aureus with no adverse hemolytic activity. Notably, these polymers also did not result in any measurable resistance development in E. coli. The peptide-mimetic design principle offers significant flexibility and diversity in the creation of new antimicrobial materials and their potential biomedical applications. PMID:23832766

Rapid biological synthesis of platinum nanoparticles using Ocimum sanctum for water electrolysis applications.

PubMed

Soundarrajan, C; Sankari, A; Dhandapani, P; Maruthamuthu, S; Ravichandran, S; Sozhan, G; Palaniswamy, N

2012-06-01

The leaf extract of Ocimum sanctum was used as a reducing agent for the synthesis of platinum nanoparticles from an aqueous chloroplatinic acid (H(2)PtCl(6)·6H(2)O). A greater conversion of platinum ions to nanoparticles was achieved by employing a tulsi leaf broth with a reaction temperature of 100 °C. Energy-dispersive absorption X-ray spectroscopy confirmed the platinum particles as major constituent in the reduction process. It is evident from scanning electron microscopy that the reduced platinum particles were found as aggregates with irregular shape. Fourier-transform infrared spectroscopy revealed that the compounds such as ascorbic acid, gallic acid, terpenoids, certain proteins and amino acids act as reducing agents for platinum ions reduction. X-ray diffraction spectroscopy suggested the associated forms of platinum with other molecules and the average particle size of platinum nanoparticle was 23 nm, calculated using Scherer equation. The reduced platinum showed similar hydrogen evolution potential and catalytic activity like pure platinum using linear scan voltammetry. This environmentally friendly method of biological platinum nanoparticles production increases the rates of synthesis faster which can potentially be used in water electrolysis applications.

Using nuclear microscopy to characterize the interaction of textile-used silver nanoparticles with a biological wastewater treatment system

NASA Astrophysics Data System (ADS)

Bento, J. B.; Franca, R. D. G.; Pinheiro, T.; Alves, L. C.; Pinheiro, H. M.; Lourenço, N. D.

2017-08-01

The use of engineered nanoparticles in the textile industry has been rapidly increasing but their fate during biological wastewater treatment is largely unknown. The goal of the current study was to characterize the interaction of silver nanoparticles (AgNPs), used in the textile industry, with a biological wastewater treatment system based on aerobic granular sludge (AGS). The exposure tests were performed using a laboratory-scale sequencing batch reactor (SBR) system with AGS. The behavior and fate of textile AgNPs in the AGS system was studied with nuclear microscopy techniques. Elemental maps of AGS samples collected from the SBR showed that AgNPs typically clustered in agglomerates of small dimensions (<10 μm), which were preferentially associated with extracellular polymeric substances (EPS). This preliminary study highlights the potential application of nuclear microscopy for the characterization of the behavior and fate of AgNPs in AGS. The detailed compartmentalization of AgNPs in AGS components obtained with nuclear microscopy provides new and relevant information concerning AgNPs retention. This will be important in biotechnological terms to delineate strategies for AgNPs removal from textile wastewater.

Bacteriophage lambda: The path from biology to theranostic agent.

PubMed

Catalano, Carlos E

2018-03-13

Viral particles provide an attractive platform for the engineering of semisynthetic therapeutic nanoparticles. They can be modified both genetically and chemically in a defined manner to alter their surface characteristics, for targeting specific cell types, to improve their pharmacokinetic features and to attenuate (or enhance) their antigenicity. These advantages derive from a detailed understanding of virus biology, gleaned from decades of fundamental genetic, biochemical, and structural studies that have provided mechanistic insight into virus assembly pathways. In particular, bacteriophages offer significant advantages as nanoparticle platforms and several have been adapted toward the design and engineering of "designer" nanoparticles for therapeutic and diagnostic (theranostic) applications. The present review focuses on one such virus, bacteriophage lambda; I discuss the biology of lambda, the tools developed to faithfully recapitulate the lambda assembly reactions in vitro and the observations that have led to cooptation of the lambda system for nanoparticle design. This discussion illustrates how a fundamental understanding of virus assembly has allowed the rational design and construction of semisynthetic nanoparticles as potential theranostic agents and illustrates the concept of benchtop to bedside translational research. This article is categorized under: Biology-Inspired Nanomaterials> Protein and Virus-Based Structures Biology-Inspired Nanomaterials> Nucleic Acid-Based Structures. © 2018 Wiley Periodicals, Inc.

Plasmonic colorimetric sensors based on etching and growth of noble metal nanoparticles: Strategies and applications.

PubMed

Zhang, Zhiyang; Wang, Han; Chen, Zhaopeng; Wang, Xiaoyan; Choo, Jaebum; Chen, Lingxin

2018-08-30

Plasmonic colorimetric sensors have emerged as a powerful tool in chemical and biological sensing applications due to the localized surface plasmon resonance (LSPR) extinction in the visible range. Among the plasmonic sensors, the most famous sensing mode is the "aggregation" plasmonic colorimetric sensor which is based on plasmon coupling due to nanoparticle aggregation. Herein, this review focuses on the newly-developing plasmonic colorimetric sensing mode - the etching or the growth of metal nanoparticles induces plasmon changes, namely, "non-aggregation" plasmonic colorimetric sensor. This type of sensors has attracted increasing interest because of their exciting properties of high sensitivity, multi-color changes, and applicability to make a test strip. Of particular interest, the test strip by immobilization of nanoparticles on the substrate can avoid the influence of nanoparticle auto-aggregation and increase the simplicity in storage and use. Although there are many excellent reviews available that describe the advance of plasmonic sensors, limited attention has been paid to the plasmonic colorimetric sensors based on etching or growth of metal nanoparticles. This review highlights recent progress on strategies and application of "non-aggregation" plasmonic colorimetric sensors. We also provide some personal insights into current challenges associated with "non-aggregation" plasmonic colorimetric sensors and propose future research directions. Copyright © 2018 Elsevier B.V. All rights reserved.

Biologically active nanocomposite of DNA-PbS nanoparticles: A new material for non-volatile memory devices

NASA Astrophysics Data System (ADS)

Murgunde, B. K.; Rabinal, M. K.; Kalasad, M. N.

2018-01-01

Composite films of deoxyribonucleic acid (DNA) and lead sulfide (PbS) nanoparticles are prepared to fabricate biological memory devices. A simple solution based electrografting is developed to deposit large (few cm2) uniform films of DNA:PbS on conducting substrates. The films are studied by X-ray photoelectron spectroscopy, field emission SEM, FTIR and optical spectroscopy to understand their properties. Charge transport measurements are carried out on ITO-DNA:PbS-metal junctions by cyclic voltage scans, electrical bi-stability is observed with ON/OFF ratio more than ∼104 times with good stability and endurance, such performance being rarely reported. The observed results are interpreted in the light of strong electrostatic binding of nanoparticles and DNA stands, which leads doping of Pb atoms into DNA. As a result, these devices exhibit negative differential resistance (NDR) effect due to oxidation of doped metal atoms. These composites can be the potential materials in the development of new generation non-volatile memory devices.

Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

PubMed

Burrows, Anne M; Li, Ly; Waller, Bridget M; Micheletta, Jerome

2016-04-01

Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance 'style', and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber-type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might

Nanosensors based on functionalized nanoparticles and surface enhanced raman scattering

DOEpatents

Talley, Chad E.; Huser, Thomas R.; Hollars, Christopher W.; Lane, Stephen M.; Satcher, Jr., Joe H.; Hart, Bradley R.; Laurence, Ted A.

2007-11-27

Surface-Enhanced Raman Spectroscopy (SERS) is a vibrational spectroscopic technique that utilizes metal surfaces to provide enhanced signals of several orders of magnitude. When molecules of interest are attached to designed metal nanoparticles, a SERS signal is attainable with single molecule detection limits. This provides an ultrasensitive means of detecting the presence of molecules. By using selective chemistries, metal nanoparticles can be functionalized to provide a unique signal upon analyte binding. Moreover, by using measurement techniques, such as, ratiometric received SERS spectra, such metal nanoparticles can be used to monitor dynamic processes in addition to static binding events. Accordingly, such nanoparticles can be used as nanosensors for a wide range of chemicals in fluid, gaseous and solid form, environmental sensors for pH, ion concentration, temperature, etc., and biological sensors for proteins, DNA, RNA, etc.

Toxicity Effects of Functionalized Quantum Dots, Gold and Polystyrene Nanoparticles on Target Aquatic Biological Models: A Review.

PubMed

Libralato, Giovanni; Galdiero, Emilia; Falanga, Annarita; Carotenuto, Rosa; de Alteriis, Elisabetta; Guida, Marco

2017-08-31

Nano-based products are widespread in several sectors, including textiles, medical-products, cosmetics, paints and plastics. Nanosafety and safe-by-design are driving nanoparticle (NP) production and applications through NP functionalization (@NPs). Indeed, @NPs frequently present biological effects that differ from the parent material. This paper reviews the impact of quantum dots (QDs), gold nanoparticles (AuNPs), and polystyrene-cored NPs (PSNPs), evidencing the role of NP functionalization in toxicity definition. Key biological models were taken into consideration for NP evaluation: Saccharomyces cerevisiae , fresh- (F) and saltwater (S) microalgae ( Raphidocelis subcapitata (F), Scenedesmus obliquus (F) and Chlorella spp. (F), and Phaeodactylum tricornutum (S)), Daphnia magna , and Xenopus laevis . QDs are quite widespread in technological devices, and they are known to induce genotoxicity and oxidative stress that can drastically change according to the coating employed. For example, AuNPs are frequently functionalized with antimicrobial peptides, which is shown to both increase their activity and decrease the relative environmental toxicity. P-NPs are frequently coated with NH₂ - for cationic and COOH - for anionic surfaces, but when positively charged toxicity effects can be observed. Careful assessment of functionalized and non-functionalized NPs is compulsory to also understand their potential direct and indirect effects when the coating is removed or degraded.

Preparation and characterization of alginate based-fluorescent magnetic nanoparticles for fluorescence/magnetic resonance multimodal imaging applications

NASA Astrophysics Data System (ADS)

Kwon, Yong-Su; Choi, Kee-Bong; Lim, Hyungjun; Lee, Sunghwi; Lee, Jae-Jong

2018-06-01

Simple and versatile methodologies have been reported that customize the surface of superparamagnetic iron oxide (SPIO) nanoparticles and impart additional fluorescence capabilities to these contrast agents. Herein, we present the rational design, synthesis, characterization, and biological applications of a new magnetic-based fluorescent probe. The dual modality imaging protocol was developed by labeling fluorophore with alginate natural polymers that have excellent biocompatibility and biodegradability, and using gelification method to form nanocomposites containing SPIO. The formation of alginate-based fluorescent magnetic (AFM) nanoparticles was observed in spherical and elliptical forms with a diameter of less than 500 nm by a transmission electron microscope (TEM). The fluorescent wavelength band in the range of 560 nm was also confirmed in the UV–visible spectrophotometer. In this study, we demonstrate that the multi-tasking design of AFM nanoparticles provides an ideal platform for building balanced dual-image probes of magnetic resonance imaging and optical imaging.

B cell lymphoma-2 (BCL-2) homology domain 3 (BH3) mimetics demonstrate differential activities dependent upon the functional repertoire of pro- and anti-apoptotic BCL-2 family proteins.

PubMed

Renault, Thibaud T; Elkholi, Rana; Bharti, Archana; Chipuk, Jerry E

2014-09-19

The B cell lymphoma-2 (BCL-2) family is the key mediator of cellular sensitivity to apoptosis during pharmacological interventions for numerous human pathologies, including cancer. There is tremendous interest to understand how the proapoptotic BCL-2 effector members (e.g. BCL-2-associated X protein, BAX) cooperate with the BCL-2 homology domain only (BH3-only) subclass (e.g. BCL-2 interacting mediator of death, BIM; BCL-2 interacting-domain death agonist, BID) to induce mitochondrial outer membrane permeabilization (MOMP) and apoptosis and whether these mechanisms may be pharmacologically exploited to enhance the killing of cancer cells. Indeed, small molecule inhibitors of the anti-apoptotic BCL-2 family members have been designed rationally. However, the success of these "BH3 mimetics" in the clinic has been limited, likely due to an incomplete understanding of how these drugs function in the presence of multiple BCL-2 family members. To increase our mechanistic understanding of how BH3 mimetics cooperate with multiple BCL-2 family members in vitro, we directly compared the activity of several BH3-mimetic compounds (i.e. ABT-263, ABT-737, GX15-070, HA14.1, TW-37) in biochemically defined large unilamellar vesicle model systems that faithfully recapitulate BAX-dependent mitochondrial outer membrane permeabilization. Our investigations revealed that the presence of BAX, BID, and BIM differentially regulated the ability of BH3 mimetics to derepress proapoptotic molecules from anti-apoptotic proteins. Using mitochondria loaded with fluorescent BH3 peptides and cells treated with inducers of cell death, these differences were supported. Together, these data suggest that although the presence of anti-apoptotic BCL-2 proteins primarily dictates cellular sensitivity to BH3 mimetics, additional specificity is conferred by proapoptotic BCL-2 proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Portable Nanoparticle-Based Sensors for Food Safety Assessment

PubMed Central

Bülbül, Gonca; Hayat, Akhtar; Andreescu, Silvana

2015-01-01

The use of nanotechnology-derived products in the development of sensors and analytical measurement methodologies has increased significantly over the past decade. Nano-based sensing approaches include the use of nanoparticles (NPs) and nanostructures to enhance sensitivity and selectivity, design new detection schemes, improve sample preparation and increase portability. This review summarizes recent advancements in the design and development of NP-based sensors for assessing food safety. The most common types of NPs used to fabricate sensors for detection of food contaminants are discussed. Selected examples of NP-based detection schemes with colorimetric and electrochemical detection are provided with focus on sensors for the detection of chemical and biological contaminants including pesticides, heavy metals, bacterial pathogens and natural toxins. Current trends in the development of low-cost portable NP-based technology for rapid assessment of food safety as well as challenges for practical implementation and future research directions are discussed. PMID:26690169

Quantitative nanoparticle tracking: applications to nanomedicine.

PubMed

Huang, Feiran; Dempsey, Christopher; Chona, Daniela; Suh, Junghae

2011-06-01

Particle tracking is an invaluable technique to extract quantitative and qualitative information regarding the transport of nanomaterials through complex biological environments. This technique can be used to probe the dynamic behavior of nanoparticles as they interact with and navigate through intra- and extra-cellular barriers. In this article, we focus on the recent developments in the application of particle-tracking technology to nanomedicine, including the study of synthetic and virus-based materials designed for gene and drug delivery. Specifically, we cover research where mean square displacements of nanomaterial transport were explicitly determined in order to quantitatively assess the transport of nanoparticles through biological environments. Particle-tracking experiments can provide important insights that may help guide the design of more intelligent and effective diagnostic and therapeutic nanoparticles.

Tuning the luminescence of ZnO:Eu nanoparticles for applications in biology and medicine

NASA Astrophysics Data System (ADS)

Kaszewski, Jarosław; Kiełbik, Paula; Wolska, Ewelina; Witkowski, Bartłomiej; Wachnicki, Łukasz; Gajewski, Zdzisław; Godlewski, Marek; Godlewski, Michał M.

2018-06-01

Zinc oxide nanoparticles were synthesized with microwave hydrothermal technique and tested as luminescent contrast for biological imaging. Luminescence was activated by Eu3+ ions embedded in the nanoparticle matrix in the increasing concentrations of 1, 5 and 10 %mol. It was found that europium did not create a separate crystalline phase up to the concentration as high as 5 %mol. However, Eu3+ ions did not substitute Zn2+ in the host lattice, but allocated in the low symmetry environment. It was proposed that europium was locating in the inter-grain space or on the surface of nanoparticles. The luminescence intensity in ZnO:Eu, as well as the size of particles, increased with the Eu ion concentration. Moreover, in 10 %mol Eu sample, the separate phase of Eu-hydroxide was identified with crystals of micrometre length. Interestingly, in vivo study revealed, that contrary to the in silico experiments, following gastric gavage, the brightest nanoparticle-related luminescence signal was observed at 1 %mol. concentration of Eu. Since the alimentary uptake of nanoparticles was related to their size, we concluded that the increase in luminescence at 5 and 10 %mol. Eu concentrations was associated with the largest ZnO:Eu and Eu-hydroxide particles that did not cross the gastrointestinal barrier.

Metal-based nanoparticle interactions with the nervous system: the challenge of brain entry and the risk of retention in the organism.

PubMed

Yokel, Robert; Grulke, Eric; MacPhail, Robert

2013-01-01

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical-chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in vivo methods, and very few human studies. The routes of uptake into the nervous system and mechanisms of nanoparticle uptake by cells are presented with examples. Brain nanoparticle uptake inversely correlates with size. The influence of shape has not been reported. Surface charge has not been clearly shown to affect flux across the blood-brain barrier. There is very little evidence for metal-based nanoparticle distribution into brain parenchyma. Metal-based nanoparticle disruption of the blood-brain barrier and adverse brain changes have been shown, and are more pronounced for spheres than rods. Study concentrations need to be put in exposure contexts. Work with dorsal root ganglion cells and brain cells in vitro show the potential for metal-based nanoparticles to produce toxicity. Interpretation of these results must consider the ability of nanoparticles to distribute across the barriers protecting the nervous system. Effects of the persistence of poorly soluble metal-based nanoparticles are of particular concern. Copyright © 2013 Wiley Periodicals, Inc.

Biological and Environmental Transformations of Copper-Based Nanomaterials

PubMed Central

Wang, Zhongying; Von Dem Bussche, Annette; Kabadi, Pranita K.; Kane, Agnes B.; Hurt, Robert H.

2013-01-01

Copper-based nanoparticles are an important class of materials with applications as catalysts, conductive inks, and antimicrobial agents. Environmental and safety issues are particularly important for copper-based nanomaterials because of their potential large-scale use and their high redox activity and toxicity reported from in vitro studies. Elemental nanocopper oxidizes readily upon atmospheric exposure during storage and use, so copper oxides are highly relevant phases to consider in studies of environmental and health impacts. Here we show that copper oxide nanoparticles undergo profound chemical transformations under conditions relevant to living systems and the natural environment. Copper oxide nanoparticle (CuO-NP) dissolution occurs at lysosomal pH (4-5), but not at neutral pH in pure water. Despite the near-neutral pH of cell culture medium, CuO-NPs undergo significant dissolution in media over time scales relevant to toxicity testing due to ligand-assisted ion release, in which amino acid complexation is an important contributor. Electron paramagnetic resonance (EPR) spectroscopy shows that dissolved copper in association with CuO-NPs are the primary redox-active species. CuO-NPs also undergo sulfidation by a dissolution-reprecipitation mechanism, and the new sulfide surfaces act as catalysts for sulfide oxidation. Copper sulfide NPs are found to be much less cytotoxic than CuO NPs, which is consistent with the very low solubility of CuS. Despite this low solubility of CuS, EPR studies show that sulfidated CuO continues to generate some ROS activity due to the release of free copper by H2O2 oxidation during the Fenton-chemistry-based EPR assay. While sulfidation can serve as a natural detoxification process for nanosilver and other chalcophile metals, our results suggest that sulfidation may not fully and permanently detoxify copper in biological or environmental compartments that contain reactive oxygen species. PMID:24032665

Amylin structure–function relationships and receptor pharmacology: implications for amylin mimetic drug development

PubMed Central

Bower, Rebekah L

2016-01-01

Amylin is an important, but poorly understood, 37 amino acid glucoregulatory hormone with great potential to target metabolic diseases. A working example that the amylin system is one worth developing is the FDA‐approved drug used in insulin‐requiring diabetic patients, pramlintide. However, certain characteristics of pramlintide pharmacokinetics and formulation leave considerable room for further development of amylin‐mimetic compounds. Given that amylin‐mimetic drug design and development is an active area of research, surprisingly little is known about the structure/function relationships of amylin. This is largely due to the unfavourable aggregative and solubility properties of the native peptide sequence, which are further complicated by the composition of amylin receptors. These are complexes of the calcitonin receptor with receptor activity‐modifying proteins. This review explores what is known of the structure–function relationships of amylin and provides insights that can be drawn from the closely related peptide, CGRP. We also describe how this information is aiding the development of more potent and stable amylin mimetics, including peptide hybrids. PMID:27061187

In vitro biological validation and cytocompatibility evaluation of hydrogel iron-oxide nanoparticles

NASA Astrophysics Data System (ADS)

Catalano, Enrico

2017-08-01

Superparamagnetic iron oxide nanoparticles (MNPs) have recently been investigated for their excellent biocompatibility as well as multi-purpose biomedical potential with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe3O4 magnetic nanoparticles were synthesized for possible use for induced magnetic hyperthermia, and targeted drug delivery. The coating of iron oxide nanoparticles plays a key-role to efficiently improve internalization of nanoparticles in many cell types. Targeting is also highly desirable for these applications. In this regard hydrophilic coating like chitosan was used to improve drug release. Uncoated (Fe3O4)and chitosan-coated iron oxide nanoparticles (CS-Fe3O4) were synthesized and characterized from the biological point of view. The aim of this study was to provide an in vitro evaluation of the cytocompatibility of Fe3O4 and CS-Fe3O4 MNPs by using different in vitro evaluation tests. In this context, the cytocompatibility and cytotoxic effects of uncoated and hydrogel chemically-engineered chitosan-coated iron oxide NPs were investigated according to the ISO standard 10993-5:2009. Fe3O4 and CS-Fe3O4 NPs were tested on human mammary epithelial cells (MCF-10A) by using direct and not direct contact cytotoxicity evaluation tests, by evaluating influence of the iron particles on the cytoskeleton with phalloidin/DAPI staining and in vitro cellular iron uptake with Perl's Prussian blue staining. The results indicate that uncoated and chitosan-coated iron oxide nanoparticles are cytocompatible, without negative influence on the cytoskeleton or higher accumulation of iron in the cytoplasm. Therefore, it is encouraging that our data suggest uncoated and chitosan-coated iron oxide nanoparticles have satisfactory proliferative and viability effects on MCF-10A cells. In conclusion data suggest that both MNP types may be differently aimed in biomedical application in relation

Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs.

PubMed

Li, Jianyu; Weber, Eckhard; Guth-Gundel, Sabine; Schuleit, Michael; Kuttler, Andreas; Halleux, Christine; Accart, Nathalie; Doelemeyer, Arno; Basler, Anne; Tigani, Bruno; Wuersch, Kuno; Fornaro, Mara; Kneissel, Michaela; Stafford, Alexander; Freedman, Benjamin R; Mooney, David J

2018-05-01

Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks. The composite hydrogels demonstrate feasibility of storage, and extended release of large quantities of an insulin-like growth factor-1 mimetic protein (8 mg mL -1 ) over four weeks. The release rate is primarily governed by ionic exchange and can be upregulated by low pH, which is typical for injured tissues. A rodent model of Achilles tendon injury is used to demonstrate that the composite hydrogels allow for highly extended and localized release of biological drugs in vivo, while demonstrating biodegradation and biocompatibility. These attributes make the composite hydrogel a promising system for drug delivery and regenerative medicine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Platinum Nanoparticles: Efficient and Stable Catechol Oxidase Mimetics.

PubMed

Liu, Yi; Wu, Haohao; Chong, Yu; Wamer, Wayne G; Xia, Qingsu; Cai, Lining; Nie, Zhihong; Fu, Peter P; Yin, Jun-Jie

2015-09-09

Although enzyme-like nanomaterials have been extensively investigated over the past decade, most research has focused on the peroxidase-like, catalase-like, or SOD-like activity of these nanomaterials. Identifying nanomaterials having oxidase-like activities has received less attention. In this study, we demonstrate that platinum nanoparticles (Pt NPs) exhibit catechol oxidase-like activity, oxidizing polyphenols into the corresponding o-quinones. Four unique approaches are employed to demonstrate the catechol oxidase-like activity exerted by Pt NPs. First, UV-vis spectroscopy is used to monitor the oxidation of polyphenols catalyzed by Pt NPs. Second, the oxidized products of polyphenols are identified by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution mass spectrometry (HRMS) identification. Third, electron spin resonance (ESR) oximetry techniques are used to confirm the O2 consumption during the oxidation reaction. Fourth, the intermediate products of semiquinone radicals formed during the oxidation of polyphenols are determined by ESR using spin stabilization. These results indicate Pt NPs possess catechol oxidase-like activity. Because polyphenols and related bioactive substances have been explored as potent antioxidants that could be useful for the prevention of cancer and cardiovascular diseases, and Pt NPs have been widely used in the chemical industry and medical science, it is essential to understand the potential effects of Pt NPs for altering or influencing the antioxidant activity of polyphenols.

Extracellular synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 and their biological applications.

PubMed

Singh, Priyanka; Singh, Hina; Kim, Yeon Ju; Mathiyalagan, Ramya; Wang, Chao; Yang, Deok Chun

2016-05-01

The present study highlights the microbial synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 strain, in an efficient way. The synthesized nanoparticles were characterized by ultraviolet-visible spectrophotometry, which displayed maximum absorbance at 424nm and 531nm for silver and gold nanoparticles, respectively. The spherical shape of nanoparticles was characterized by field emission transmission electron microscopy. The energy dispersive X-ray spectroscopy and elemental mapping were displayed the purity and maximum elemental distribution of silver and gold elements in the respective nanoproducts. The X-ray diffraction spectroscopy results demonstrate the crystalline nature of synthesized nanoparticles. The particle size analysis demonstrate the nanoparticles distribution with respect to intensity, volume and number of nanoparticles. For biological applications, the silver nanoparticles have been explored in terms of MIC and MBC against pathogenic microorganisms such as Vibrio parahaemolyticus, Escherichia coli, Salmonella enterica, Bacillus anthracis, Bacillus cereus and Staphylococcus aureus. Moreover, the silver nanoparticles in combination with commercial antibiotics, such as vancomycin, rifampicin, oleandomycin, penicillin G, novobiocin, and lincomycin have been explored for the enhancement of antibacterial activity and the obtained results showed that 3μg concentration of silver nanoparticles sufficiently enhance the antimicrobial efficacy of commercial antibiotics against pathogenic microorganism. Furthermore, the silver nanoparticles potential has been reconnoitered for the biofilm inhibition by S. aureus, Pseudomonas aeruginosa and E. coli and the results revealed sufficient activity at 6μg concentration. In addition, gold nanoparticles have been applied for catalytic activity, for the reduction of 4-nitrophenol to 4-aminophenol using sodium borohydride and positive results were attained. Copyright © 2016 Elsevier Inc. All

Nanoparticles in the clinic

PubMed Central

Anselmo, Aaron C.

2016-01-01

Abstract Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems. PMID:29313004

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

HDL mimetic CER-001 targets atherosclerotic plaques in patients.

PubMed

Zheng, Kang He; van der Valk, Fleur M; Smits, Loek P; Sandberg, Mara; Dasseux, Jean-Louis; Baron, Rudi; Barbaras, Ronald; Keyserling, Constance; Coolen, Bram F; Nederveen, Aart J; Verberne, Hein J; Nell, Thijs E; Vugts, Danielle J; Duivenvoorden, Raphaël; Fayad, Zahi A; Mulder, Willem J M; van Dongen, Guus A M S; Stroes, Erik S G

2016-08-01

Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p < 0.001). Using serial PET/CT imaging, we showed that arterial uptake of CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p < 0.001). Plaque TBRmax correlated with local plaque contrast enhancement (r = 0.56; p = 0.019) as assessed by CE-MRI. Infusion of HDL mimetic CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. Netherlands Trial Registry - NTR5178. http

Preferential binding of positive nanoparticles on cell membranes is due to electrostatic interactions: A too simplistic explanation that does not take into account the nanoparticle protein corona.

PubMed

Forest, Valérie; Pourchez, Jérémie

2017-01-01

The internalization of nanoparticles by cells (and more broadly the nanoparticle/cell interaction) is a crucial issue both for biomedical applications (for the design of nanocarriers with enhanced cellular uptake to reach their intracellular therapeutic targets) and in a nanosafety context (as the internalized dose is one of the key factors in cytotoxicity). Many parameters can influence the nanoparticle/cell interaction, among them, the nanoparticle physico-chemical features, and especially the surface charge. It is generally admitted that positive nanoparticles are more uptaken by cells than neutral or negative nanoparticles. It is supposedly due to favorable electrostatic interactions with negatively charged cell membrane. However, this theory seems too simplistic as it does not consider a fundamental element: the nanoparticle protein corona. Indeed, once introduced in a biological medium nanoparticles adsorb proteins at their surface, forming a new interface defining the nanoparticle "biological identity". This adds a new level of complexity in the interactions with biological systems that cannot be any more limited to electrostatic binding. These interactions will then influence cell behavior. Based on a literature review and on an example of our own experience the parameters involved in the nanoparticle protein corona formation as well as in the nanoparticle/cell interactions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

A proposed CT contrast agent using carboxybetaine zwitterionic tantalum oxide nanoparticles: Imaging, biological, and physicochemical performance

PubMed Central

FitzGerald, Paul F.; Butts, Matthew D.; Roberts, Jeannette C.; Colborn, Robert E.; Torres, Andrew S.; Lee, Brian D.; Yeh, Benjamin M.; Bonitatibus, Peter J.

2016-01-01

Objectives To produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ) coated soluble tantalum oxide nanoparticles (CZ-TaO NPs). We chose tantalum to provide superior imaging performance compared to current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. The aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared to clinically-used iodinated agents. Materials and Methods We evaluated CT imaging performance of our CZ-TaO NPs compared to an iodinated agent in live rats, imaged centrally-located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats’ great vessels at high temporal resolution during and following contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. CZ-TaO NPs were synthesized and analyzed in detail. We used multi-dimensional nuclear magnetic resonance (NMR) to determine surface functionality of the nanoparticles. We measured nanoparticle size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including

Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

NASA Astrophysics Data System (ADS)

Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

2012-02-01

Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

Additional records and descriptions of the ant-mimetic plant bug genus Pilophorus from Thailand (Hemiptera: Heteroptera: Miridae: Phylinae: Pilophorini).

PubMed

Yasunaga, Tomohide; Yamada, Kazutaka; Artchawakom, Taksin

2014-05-09

Eleven species of the ant-mimetic plant bug genus Pilophorus Hahn from Thailand are documented, with photographic images of live individuals. Four new species with conventional, moderate antlike shape, Pilophorus meteorus, P. saovapruki, P. subparallelus and P. suwimonae, are described. Two known Thai species, P. alstoni Schuh and P. typicus (Distant), are further reported and diagnosed. Biological information including host association is provided for P. alstoni, P. meteorus, P. saovapruki and P. typicus. A checklist of all currently known species of Pilophorus in Thailand and a key to known Thai species are included. Pilophorus typicus is reported from Singapore for the first time.

Synthesis of Gold Nanoparticles with Buffer-Dependent Variations of Size and Morphology in Biological Buffers.

PubMed

Ahmed, Syed Rahin; Oh, Sangjin; Baba, Rina; Zhou, Hongjian; Hwang, Sungu; Lee, Jaebeom; Park, Enoch Y

2016-12-01

The demand for biologically compatible and stable noble metal nanoparticles (NPs) has increased in recent years due to their inert nature and unique optical properties. In this article, we present 11 different synthetic methods for obtaining gold nanoparticles (Au NPs) through the use of common biological buffers. The results demonstrate that the sizes, shapes, and monodispersity of the NPs could be varied depending on the type of buffer used, as these buffers acted as both a reducing agent and a stabilizer in each synthesis. Theoretical simulations and electrochemical experiments were performed to understand the buffer-dependent variations of size and morphology exhibited by these Au NPs, which revealed that surface interactions and the electrostatic energy on the (111) surface of Au were the determining factors. The long-term stability of the synthesized NPs in buffer solution was also investigated. Most NPs synthesized using buffers showed a uniquely wide range of pH stability and excellent cell viability without the need for further modifications.

Synthesis and Characterization of BSA Conjugated Silver Nanoparticles (Ag/BSA Nanoparticles) and Evaluation of Biological Properties of Ag/BSA Nanoparticles and Ag/BSA Nanoparticles Loaded Poly(hydroxy butyrate valerate) PHBV Films

NASA Astrophysics Data System (ADS)

Ambaye, Almaz

Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa are the etiological agents of several infectious diseases. Antibiotic resistance by these three microbes has emerged as a prevalent problem due in part to the misuse of existing antibiotics and the lack of novel antibiotics. Nanoparticles have emerged as an alternative antibacterial agents to conventional antibiotics owing to their high surface area to volume ratio and their unique chemical and physical properties. Among the nanoparticles, silver nanoparticles have gained increasing attention because silver nanoparticles exhibit antibacterial activity against a range of gram positive and gram negative bacteria. Nanoparticles of well-defined chemistry and morphology can be used in broad biomedical applications, especially in bone tissue engineering applications, where bone infection by bacteria can be acute and lethal. It is commonly noted in the literature that the activity of nanoparticles against microorganisms is dependent upon the size and concentration of the nanoparticles as well as the chemistry of stabilizing agent. To the best of our knowledge, a comprehensive study that evaluates the antibacterial activity of well characterized silver nanoparticles in particular Bovine Serum Albumin (BSA) stabilized against S. aureus and E. coli and cytotoxicity level of BSA stabilized silver nanoparticles towards osteoblast cells (MC3T3-E1) is currently lacking. Therefore, the primary objective of this study was to characterize protein conjugated silver nanoparticles prepared by chemical reduction of AgNO3 and BSA mixture. The formation of Ag/BSA nanoparticles was studied by UV-Vis spectroscopy. The molar ratio of silver to BSA in the Ag/BSA nanoparticles was established to be 27+/- 3: 1, based on Thermogravimetric Analysis and Atomic Absorption Spectroscopy. Based on atomic force microscopy, dynamic light scattering,and transmission electron microscopy(TEM) measurements, the particle size (diameter) of

Number of Nanoparticles per Cell through a Spectrophotometric Method - A key parameter to Assess Nanoparticle-based Cellular Assays.

PubMed

Unciti-Broceta, Juan D; Cano-Cortés, Victoria; Altea-Manzano, Patricia; Pernagallo, Salvatore; Díaz-Mochón, Juan J; Sánchez-Martín, Rosario M

2015-05-15

Engineered nanoparticles (eNPs) for biological and biomedical applications are produced from functionalised nanoparticles (NPs) after undergoing multiple handling steps, giving rise to an inevitable loss of NPs. Herein we present a practical method to quantify nanoparticles (NPs) number per volume in an aqueous suspension using standard spectrophotometers and minute amounts of the suspensions (up to 1 μL). This method allows, for the first time, to analyse cellular uptake by reporting NPs number added per cell, as opposed to current methods which are related to solid content (w/V) of NPs. In analogy to the parameter used in viral infective assays (multiplicity of infection), we propose to name this novel parameter as multiplicity of nanofection.

Design, synthesis and biological evaluation of non-peptide PAR1 thrombin receptor antagonists based on small bifunctional templates: arginine and phenylalanine side chain groups are keys for receptor activity.

PubMed

Androutsou, Maria-Eleni; Saifeddine, Mahmoud; Hollenberg, Morley D; Matsoukas, John; Agelis, George

2010-04-01

In the present study, we report the synthesis and biological evaluation of a series of new non-peptide PAR(1) mimetic receptor antagonists, based on conformational analysis of the S(42)FLLR(46) tethered ligand (TL) sequence of PAR(1). These compounds incorporate the key pharmacophore groups in the TL sequence, guanidyl, amino and phenyl, which are essential for triggering receptor activity. Compounds 5 and 15 (50-100 microM) inhibited both TFLLR-amide (10 microM) and thrombin-mediated (0.5 and 1 U/ml; 5 and 10 microM) calcium signaling in a cultured human HEK cell assay.

DRP-1 is required for BH3 mimetic-mediated mitochondrial fragmentation and apoptosis

PubMed Central

Milani, Mateus; Byrne, Dominic P; Greaves, Georgia; Butterworth, Michael; Cohen, Gerald M; Eyers, Patrick A; Varadarajan, Shankar

2017-01-01

The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context. To address the lack of standardised assays for benchmarking the in vitro binding of putative inhibitors before analysis of their cellular effects, we developed a rapid differential scanning fluorimetry (DSF)-based assay, and used it to screen a panel of BH3 mimetics. We next contrasted their binding signatures with their ability to induce apoptosis in a MCL-1 dependent cell line. Of all the MCL-1 inhibitors tested, only A-1210477 induced rapid, concentration-dependent apoptosis, which strongly correlated with a thermal protective effect on MCL-1 in the DSF assay. In cells that depend on both MCL-1 and BCL-XL, A-1210477 exhibited marked synergy with A-1331852, a BCL-XL specific inhibitor, to induce cell death. Despite this selectivity and potency, A-1210477 induced profound structural changes in the mitochondrial network in several cell lines that were not phenocopied following MCL-1 RNA interference or transcriptional repression, suggesting that A-1210477 induces mitochondrial fragmentation in an MCL-1-independent manner. However, A-1210477-induced mitochondrial fragmentation was dependent upon DRP-1, and silencing expression levels of DRP-1 diminished not just mitochondrial fragmentation but also BH3 mimetic-mediated apoptosis. These findings provide new insights into MCL-1 ligands, and the interplay between DRP-1 and the anti-apoptotic BCL-2 family members in the regulation of apoptosis. PMID:28079887

Antimicrobial property of zinc based nanoparticles

NASA Astrophysics Data System (ADS)

Chiriac, V.; Stratulat, D. N.; Calin, G.; Nichitus, S.; Burlui, V.; Stadoleanu, C.; Popa, M.; Popa, I. M.

2016-06-01

Pathogen bacteria strains with wide spectrum can cause serious infections with drastic damages on humans. There are studies reflecting antibacterial effect of nanoparticles type metal or metal oxides as an alternative or concurrent treatment to the diseases caused by infectious agents. Synthesised nanoparticles using different methods like sol-gel, hydrothermal or plant extraction were tested following well-established protocols with the regard to their antimicrobial activity. It was found that zinc based nanoparticles possess strong synergistic effect with commonly used antibiotics on infection tratment.

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

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

Hanns-Rudolf, Paur; Cassee, Flemming R.; Teeguarden, Justin G.

The rapid introduction of engineered nanostructured materials into numerous industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of consumer products. The dynamic development of new nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety. In this consensus document from a workshop on in-vitro cell systems for nanotoxicity testing an overview is given of the main issues concerningmore » inhalation exposure to nanoparticles, lung physiology, nanoparticle-related biological mechanisms, in-vitro cell exposure systems for nanoparticles and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanotoxicity. For the investigation of pulmonary nanotoxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.« less

Substrate-Independent Robust and Heparin-Mimetic Hydrogel Thin Film Coating via Combined LbL Self-Assembly and Mussel-Inspired Post-Cross-linking.

PubMed

Ma, Lang; Cheng, Chong; He, Chao; Nie, Chuanxiong; Deng, Jie; Sun, Shudong; Zhao, Changsheng

2015-12-02

Staphylococcus aureus bacteria. Combined the above advantages, it is believed that the designed heparin-mimetic hydrogel thin films may show high potential for applications in various biological and clinical fields, such as long-term hemocompatible and drug-loading materials for implants.

Engineering Persistent Luminescence Nanoparticles for Biological Applications: From Biosensing/Bioimaging to Theranostics.

PubMed

Sun, Shao-Kai; Wang, He-Fang; Yan, Xiu-Ping

2018-05-15

Persistent luminescence nanoparticles (PLNPs) are unique optical materials emitting long-lasting luminescence after ceasing excitation. Such a unique optical feature allows luminescence detection without constant external illumination to avoid the interferences of autofluorescence and scattering light from biological fluids and tissues. Besides, near-infrared (NIR) PLNPs have advantages of deep penetration and the reactivation of the persistent luminescence (PL) by red or NIR light. These features make the application of NIR-emitting PLNPs in long-term bioimaging no longer limited by the lifetime of PL. To take full advantage of PLNPs for biological applications, the versatile strategies for bridging PLNPs and biological system become increasingly significant for the design of PLNPs-based nanoprobes. In this Account, we summarize our systematic achievements in the biological applications of PLNPs from biosensing/bioimaging to theranostics with emphasizing the engineering strategies for fabricating specific PLNPs-based nanoprobes. We take surface engineering and manipulating energy transfer as the major principles to design various PLNPs-based nanoprobes based on the nature of interactions between nanoprobes and targets. We have developed target-induced formation or interruption of fluorescence resonance energy transfer systems for autofluorescence-free biosensing and imaging of cancer biomarkers. We have decorated single or dual targeting ligands on PLNPs for tumor-targeted imaging, and integrated other modal imaging agents into PLNPs for multimodal imaging. We have also employed specific functionalization for various biomedical applications including chemotherapy, photodynamic therapy, photothermal therapy, stem cells tracking and PL imaging-guided gene therapy. Besides, we have modified PLNPs with multiple functional units to achieve challenging metastatic tumor theranostics. The proposed design principle and comprehensive strategies show great potential in

Magnetic nanoparticles based cancer therapy: current status and applications.

PubMed

Zhang, Huan; Liu, Xiao Li; Zhang, Yi Fan; Gao, Fei; Li, Ga Long; He, Yuan; Peng, Ming Li; Fan, Hai Ming

2018-04-01

Nanotechnology holds a promising potential for developing biomedical nanoplatforms in cancer therapy. The magnetic nanoparticles, which integrate uniquely appealing features of magnetic manipulation, nanoscale heat generator, localized magnetic field and enzyme-mimics, prompt the development and application of magnetic nanoparticles-based cancer medicine. Considerable success has been achieved in improving the magnetic resonance imaging (MRI) sensitivity, and the therapeutic function of the magnetic nanoparticles should be given adequate attention. This work reviews the current status and applications of magnetic nanoparticles based cancer therapy. The advantages of magnetic nanoparticles that may contribute to improved therapeutics efficacy of clinic cancer treatment are highlighted here.

Beyond dRGT as mimetic massive gravity

NASA Astrophysics Data System (ADS)

Golovnev, Alexey

2018-04-01

An interesting proposal has recently been made to extend massive gravity models beyond dRGT by a disformal transformation of the metric. In this Letter we want to note that it can be viewed as a mimetic extension of dRGT gravity which enormously simplifies the Hamiltonian analysis. In particular, pure gravity sector is equivalent to the usual dRGT gravity coupled to a constrained scalar field. And we also give some comments about possible matter couplings.

Synthesis of highly stable cyanine-dye-doped silica nanoparticle for biological applications

NASA Astrophysics Data System (ADS)

Lian, Ying; Ding, Long-Jiang; Zhang, Wei; Zhang, Xiao-ai; Zhang, Ying-Lu; Lin, Zhen-zhen; Wang, Xu-dong

2018-07-01

Cyanine dyes are widely used in biological labeling and imaging because of their narrow near infrared emission, good brightness and high flexibility in functionalization, which not only enables multiplex analysis and multi-color imaging, but also greatly reduces autofluorescence from biological matter and increases signal-to-noise ratio. Unfortunately, their poor chemical- and photo-stability strongly limits their applications. The incorporation of cyanine dyes in silica nanoparticles provides a solution to the problem. On one hand, the incorporation of cyanine dyes in silica matrix can enhance their chemical- and photo-stability and increase brightness of the nanomaterials. On the other hand, silica matrix provides an optimized condition to host the dye, which helps to maintain their fluorescent properties during application. In addition, the well-established silane technique provides numerous functionalities for diverse applications. However, commercially available cyanine dyes are not very stable at high alkaline conditions, which will gradually lose their fluorescence over time. Our results showed that cyanine dyes are very vulnerable in the reverse micelle system, in which they will lose their fluorescence in less than half an hour. The existence of surfactant could greatly promote degradation of cyanine dyes. Fluorescent silica nanoparticles cannot be obtained at the high alkaline condition with the existence of surfactant. In contrast, the cyanine dyes are relatively stable in Stöber media. Owing to the fast formation of silica particles in Stöber media, the exposure time of cyanine dye in alkaline solution was greatly reduced, and highly fluorescent particles with good morphology and size distribution could be obtained via Stöber approach. However, the increasing water content in the Stöber could reduce the stability of cyanine dyes, which should be avoided. This research here provides a clear guidance on how to successfully synthesize cyanine dye

In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles.

PubMed

Esmaeili, Akbar; Asgari, Azadeh

2015-11-01

In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality. Copyright © 2015 Elsevier B.V. All rights reserved.

Polymeric nanoparticles

PubMed Central

Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

2014-01-01

Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems. PMID:24128651

Helium-based cold atmospheric plasma-induced reactive oxygen species-mediated apoptotic pathway attenuated by platinum nanoparticles.

PubMed

Jawaid, Paras; Rehman, Mati Ur; Zhao, Qing Li; Takeda, Keigo; Ishikawa, Kenji; Hori, Masaru; Shimizu, Tadamichi; Kondo, Takashi

2016-09-01

Plasma is generated by ionizing gas molecules. Helium (He)-based cold atmospheric plasma (CAP) was generated using a high-voltage power supply with low-frequency excitation (60 Hz at 7 kV) and He flow at 2 l/min. Platinum nanoparticles (Pt-NPs) are potent antioxidants due to their unique ability to scavenge superoxides and peroxides. These features make them useful for the protection against oxidative stress-associated pathologies. Here, the effects of Pt-NPs on He-CAP-induced apoptosis and the underlying mechanism were examined in human lymphoma U937 cells. Apoptosis was measured after cells were exposed to He-CAP in the presence or absence of Pt-NPs. The effects of combined treatment were determined by observing the changes in intracellular reactive oxygen species (ROS) and both mitochondrial and Fas dependent pathway. The results indicate that Pt-NPs substantially scavenge He-CAP-induced superoxides and peroxides and inhibit all the pathways involved in apoptosis execution. This might be because of the SOD/catalase mimetic effects of Pt-NPs. These results showed that the Pt-NPs can induce He-CAP desensitization in human lymphoma U937 cells. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles.

PubMed

Pooja, Deep; Babu Bikkina, Dileep J; Kulhari, Hitesh; Nikhila, Nalla; Chinde, Srinivas; Raghavendra, Y M; Sreedhar, B; Tiwari, Ashok K

2014-08-01

Silibinin is reported to possess multiple biological activities. However, its hydrophobic nature limits its bioavailability compromising in vivo biological activities. Nanoparticles-based delivery of such molecules has emerged as new technique to resolve these issues. Bio-degradable, compatible and adhesive nature of chitosan has recently attracted its suitability as a carrier for biologically active molecules. This study presents fabrication and characterization of chitosan-tripolyphosphate based encapsulation of silibinin. Various preparations of silibinin encapsulated chitosan-tripolyphosphate nanoparticles were studied for particle size, morphology, zeta-potential, and encapsulation efficiencies. Preparations were also evaluated for cytotoxic activities in vitro. The optimized silibinin loaded chitosan nanoparticles were of 263.7±4.1nm in particle size with zeta potential 37.4±1.57mV. Nanoparticles showed high silibinin encapsulation efficiencies (82.94±1.82%). No chemical interactions between silibinin and chitosan were observed in FTIR analysis. Powder X-ray diffraction analysis revealed transformed physical state of silibinin after encapsulation. Surface morphology and thermal behaviour were determined using TEM and DSC analysis. Encapsulated silibinin displayed increased dissolution and better cytotoxicity against human prostate cancer cells (DU145) than silibinin alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Silver Nanoparticle Impregnated Bio-Based Activated Carbon with Enhanced Antimicrobial Activity

NASA Astrophysics Data System (ADS)

Selvakumar, R.; Suriyaraj, S. P.; Jayavignesh, V.; Swaminathan, K.

2013-08-01

The present study involves the production of silver nanoparticles using a novel yeast strain Saccharomyces cerevisiae BU-MBT CY-1 isolated from coconut cell sap. The biological reduction of silver nitrate by the isolate was deducted at various time intervals. The yeast cells after biological silver reduction were harvested and subjected to carbonization at 400°C for 1 h and its properties were analyzed using Fourier transform infra-red spectroscopy, X-ray diffraction, scanning electron microscope attached with energy dispersive spectroscopy and transmission electron microscopy. The average size of the silver nanoparticles present on the surface of the carbonized silver containing yeast cells (CSY) was 19 ± 9 nm. The carbonized control yeast cells (CCY) did not contain any particles on its surface. The carbonized silver nanoparticles containing yeast cells (CSY) were made into bioactive emulsion and tested for its efficacy against various pathogenic Gram positive and Gram negative bacteria. The antimicrobial activity studies indicated that CSY bioactive nanoemulsion was effective against Gram negative organisms than Gram positive organism.

Lipid-lipid and lipid-drug interactions in biological membranes

NASA Astrophysics Data System (ADS)

Martynowycz, Michael W.

Interactions between lipids and drug molecules in biological membranes help govern proper biological function in organisms. The mechanisms responsible for hydrophobic drug permeation remain elusive. Many small molecule drugs are hydrophobic. These drugs inhibit proteins in the cellular interior. The rise of antibiotic resistance in bacteria is thought to be caused by mutations in protein structure, changing drug kinetics to favor growth. However, small molecule drugs have been shown to have different mechanisms depending in the structure of the lipid membrane of the target cell. Biological membranes are investigated using Langmuir monolayers at the air-liquid interface. These offer the highest level of control in the mimetic system and allow them to be investigated using complementary techniques. Langmuir isotherms and insertion assays are used to determine the area occupied by each lipid in the membrane and the change in area caused by the introduction of a drug molecule, respectively. Specular X-ray reflectivity is used to determine the electron density of the monolayer, and grazing incidence X-ray diffraction is used to determine the in-plane order of the monolayer. These methods determine the affinity of the drug and the mechanism of action. Studies are presented on hydrophobic drugs with mammalian membrane mimics using warfarin along with modified analogues, called superwarfarins. Data shows that toxicity of these modified drugs are modulated by the membrane cholesterol content in cells; explaining several previously unexplained effects of the drugs. Membrane mimics of bacteria are investigated along with their interactions with a hydrophobic antibiotic, novobiocin. Data suggests that permeation of the drug is mediated by modifications to the membrane lipids, and completely ceases translocation under certain circumstances. Circumventing deficiencies in small, hydrophobic drugs is approached by using biologically mimetic oligomers. Peptoids, mimetic of host

Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states

PubMed Central

Pulido-Reyes, Gerardo; Rodea-Palomares, Ismael; Das, Soumen; Sakthivel, Tamil Selvan; Leganes, Francisco; Rosal, Roberto; Seal, Sudipta; Fernández-Piñas, Francisca

2015-01-01

Cerium oxide nanoparticles (nanoceria; CNPs) have been found to have both pro-oxidant and anti-oxidant effects on different cell systems or organisms. In order to untangle the mechanisms which underlie the biological activity of nanoceria, we have studied the effect of five different CNPs on a model relevant aquatic microorganism. Neither shape, concentration, synthesis method, surface charge (ζ-potential), nor nominal size had any influence in the observed biological activity. The main driver of toxicity was found to be the percentage of surface content of Ce3+ sites: CNP1 (58%) and CNP5 (40%) were found to be toxic whereas CNP2 (28%), CNP3 (36%) and CNP4 (26%) were found to be non-toxic. The colloidal stability and redox chemistry of the most and least toxic CNPs, CNP1 and CNP2, respectively, were modified by incubation with iron and phosphate buffers. Blocking surface Ce3+ sites of the most toxic CNP, CNP1, with phosphate treatment reverted toxicity and stimulated growth. Colloidal destabilization with Fe treatment only increased toxicity of CNP1. The results of this study are relevant in the understanding of the main drivers of biological activity of nanoceria and to define global descriptors of engineered nanoparticles (ENPs) bioactivity which may be useful in safer-by-design strategies of nanomaterials. PMID:26489858

Mapping of native inorganic elements and injected nanoparticles in a biological organ with laser-induced plasma

NASA Astrophysics Data System (ADS)

Motto-Ros, V.; Sancey, L.; Ma, Q. L.; Lux, F.; Bai, X. S.; Wang, X. C.; Yu, Jin; Panczer, G.; Tillement, O.

2012-11-01

Emission spectroscopy of laser-induced plasma from a thin section of mouse kidney successfully detected inorganic elements, Na, Ca, Cu, and Gd, naturally contained in the organ or artificially injected in the form of Gd-based nanoparticle. A two-dimensional scan of the sample allowed the laser beam to explore its surface with a resolution of 100 μm, resulting in a quantitative elemental mapping of the organ with sub-mM sensitivity. The compatibility of the setup with standard optical microscopy emphasizes the potential to provide multiple images of a same biological tissue with different types of response which can be elemental, molecular, or cellular.

The mimetic repertoire of the spotted bowerbird Ptilonorhynchus maculatus

NASA Astrophysics Data System (ADS)

Kelley, Laura A.; Healy, Susan D.

2011-06-01

Although vocal mimicry in songbirds is well documented, little is known about the function of such mimicry. One possibility is that the mimic produces the vocalisations of predatory or aggressive species to deter potential predators or competitors. Alternatively, these sounds may be learned in error as a result of their acoustic properties such as structural simplicity. We determined the mimetic repertoires of a population of male spotted bowerbirds Ptilonorhynchus maculatus, a species that mimics predatory and aggressive species. Although male mimetic repertoires contained an overabundance of vocalisations produced by species that were generally aggressive, there was also a marked prevalence of mimicry of sounds that are associated with alarm such as predator calls, alarm calls and mobbing calls, irrespective of whether the species being mimicked was aggressive or not. We propose that it may be the alarming context in which these sounds are first heard that may lead both to their acquisition and to their later reproduction. We suggest that enhanced learning capability during acute stress may explain vocal mimicry in many species that mimic sounds associated with alarm.

Synthesis, surface modification and biological imaging of aggregation-induced emission (AIE) dye doped silica nanoparticles

NASA Astrophysics Data System (ADS)

Mao, Liucheng; Liu, Meiying; Xu, Dazhuang; Wan, Qing; Huang, Qiang; Jiang, Ruming; Shi, Yingge; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-05-01

Fluorescent silica nanoparticles (FSNPs) have been extensively investigated for various biomedical applications in recently years. However, the aggregation of organic dyes in silica nanoparticles also leads the significant fluorescence quenching owing to the aggregation caused quenching effects of organic dyes. Herein, we developed a rather facile strategy to fabricate FSNPs with desirable fluorescent properties through non-covalent incorporation of fluorophores with aggregation-induced emission (AIE) feature into silica nanoparticles, which were subsequently modified with functional polymers. The resultant FSNPs polymer nanocomposites (named as FSNPs-poly(IA-co-PEGMA)) exhibited uniform spherical morphology, high water dispersiity, and bright red fluorescence. Cytotoxicity results indicate that FSNPs-poly(IA-co-PEGMA) possess excellent biocompatibility. Cell uptake behavior suggests FSNPs-poly(IA-co-PEGMA) are of great potential for biological imaging applications. Taken together, we have reported a facile method for the fabrication of FSNPs through non-covalent encapsulation using an AIE-active dye. These FSNPs can be further functionalized with functional polymers through ring-opening reaction and the resultant FSNPs-poly(IA-co-PEGMA) showed great potential for biological imaging. More importantly, we believe that many other functional components could also be integrated into these FSNPs through the facile ring-opening reaction. Therefore, this method should be a facile and general tool for fabrication of polymer functionalized AIE-active FSNPs.

Characterization of KCNE1 inside Lipodisq Nanoparticles for EPR Spectroscopic Studies of Membrane Proteins.

PubMed

Sahu, Indra D; Zhang, Rongfu; Dunagan, Megan M; Craig, Andrew F; Lorigan, Gary A

2017-06-01

EPR spectroscopic studies of membrane proteins in a physiologically relevant native membrane-bound state are extremely challenging due to the complexity observed in inhomogeneity sample preparation and dynamic motion of the spin-label. Traditionally, detergent micelles are the most widely used membrane mimetics for membrane proteins due to their smaller size and homogeneity, providing high-resolution structure analysis by solution NMR spectroscopy. However, it is often difficult to examine whether the protein structure in a micelle environment is the same as that of the respective membrane-bound state. Recently, lipodisq nanoparticles have been introduced as a potentially good membrane mimetic system for structural studies of membrane proteins. However, a detailed characterization of a spin-labeled membrane protein incorporated into lipodisq nanoparticles is still lacking. In this work, lipodisq nanoparticles were used as a membrane mimic system for probing the structural and dynamic properties of the integral membrane protein KCNE1 using site-directed spin labeling EPR spectroscopy. The characterization of spin-labeled KCNE1 incorporated into lipodisq nanoparticles was carried out using CW-EPR titration experiments for the EPR spectral line shape analysis and pulsed EPR titration experiment for the phase memory time (T m ) measurements. The CW-EPR titration experiment indicated an increase in spectral line broadening with the addition of the SMA polymer which approaches close to the rigid limit at a lipid to polymer weight ratio of 1:1, providing a clear solubilization of the protein-lipid complex. Similarly, the T m titration experiment indicated an increase in T m values with the addition of SMA polymer and approaches ∼2 μs at a lipid to polymer weight ratio of 1:2. Additionally, CW-EPR spectral line shape analysis was performed on six inside and six outside the membrane spin-label probes of KCNE1 in lipodisq nanoparticles. The results indicated significant

Photoactivatable fluorescent probes reveal heterogeneous nanoparticle permeation through biological gels at multiple scales

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

Schuster, Benjamin S.; Allan, Daniel B.; Kays, Joshua C.

Diffusion through biological gels is crucial for effective drug delivery using nanoparticles. Here, we demonstrate a new method to measure diffusivity over a large range of length scales – from tens of nanometers to tens of micrometers – using photoactivatable fluorescent nanoparticle probes. We have applied this method to investigate the length-scale dependent mobility of nanoparticles in fibrin gels and in sputum from patients with cystic fibrosis (CF). Nanoparticles composed of poly(lactic-co-glycolic acid), with polyethylene glycol coatings to resist bioadhesion, were internally labeled with caged rhodamine to make the particles photoactivatable. We activated particles within a region of sample usingmore » brief, targeted exposure to UV light, uncaging the rhodamine and causing the particles in that region to become fluorescent. We imaged the subsequent spatiotemporal evolution in fluorescence intensity and observed the collective particle diffusion over tens of minutes and tens of micrometers. We also performed complementary multiple particle tracking experiments on the same particles, extending significantly the range over which particle motion and its heterogeneity can be observed. In fibrin gels, both methods showed an immobile fraction of particles and a mobile fraction that diffused over all measured length scales. In the CF sputum, particle diffusion was spatially heterogeneous and locally anisotropic but nevertheless typically led to unbounded transport extending tens of micrometers within tens of minutes. Lastly, these findings provide insight into the mesoscale architecture of these gels and its role in setting their permeability on physiologically relevant length scales, pointing toward strategies for improving nanoparticle drug delivery.« less

Photoactivatable fluorescent probes reveal heterogeneous nanoparticle permeation through biological gels at multiple scales

DOE PAGES

Schuster, Benjamin S.; Allan, Daniel B.; Kays, Joshua C.; ...

2017-05-31

Diffusion through biological gels is crucial for effective drug delivery using nanoparticles. Here, we demonstrate a new method to measure diffusivity over a large range of length scales – from tens of nanometers to tens of micrometers – using photoactivatable fluorescent nanoparticle probes. We have applied this method to investigate the length-scale dependent mobility of nanoparticles in fibrin gels and in sputum from patients with cystic fibrosis (CF). Nanoparticles composed of poly(lactic-co-glycolic acid), with polyethylene glycol coatings to resist bioadhesion, were internally labeled with caged rhodamine to make the particles photoactivatable. We activated particles within a region of sample usingmore » brief, targeted exposure to UV light, uncaging the rhodamine and causing the particles in that region to become fluorescent. We imaged the subsequent spatiotemporal evolution in fluorescence intensity and observed the collective particle diffusion over tens of minutes and tens of micrometers. We also performed complementary multiple particle tracking experiments on the same particles, extending significantly the range over which particle motion and its heterogeneity can be observed. In fibrin gels, both methods showed an immobile fraction of particles and a mobile fraction that diffused over all measured length scales. In the CF sputum, particle diffusion was spatially heterogeneous and locally anisotropic but nevertheless typically led to unbounded transport extending tens of micrometers within tens of minutes. Lastly, these findings provide insight into the mesoscale architecture of these gels and its role in setting their permeability on physiologically relevant length scales, pointing toward strategies for improving nanoparticle drug delivery.« less

Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids

PubMed Central

Jin, Haibao; Jiao, Fang; Daily, Michael D.; Chen, Yulin; Yan, Feng; Ding, Yan-Huai; Zhang, Xin; Robertson, Ellen J.; Baer, Marcel D.; Chen, Chun-Long

2016-01-01

An ability to develop sequence-defined synthetic polymers that both mimic lipid amphiphilicity for self-assembly of highly stable membrane-mimetic 2D nanomaterials and exhibit protein-like functionality would revolutionize the development of biomimetic membranes. Here we report the assembly of lipid-like peptoids into highly stable, crystalline, free-standing and self-repairing membrane-mimetic 2D nanomaterials through a facile crystallization process. Both experimental and molecular dynamics simulation results show that peptoids assemble into membranes through an anisotropic formation process. We further demonstrated the use of peptoid membranes as a robust platform to incorporate and pattern functional objects through large side-chain diversity and/or co-crystallization approaches. Similar to lipid membranes, peptoid membranes exhibit changes in thickness upon exposure to external stimuli; they can coat surfaces in single layers and self-repair. We anticipate that this new class of membrane-mimetic 2D nanomaterials will provide a robust matrix for development of biomimetic membranes tailored to specific applications. PMID:27402325

Gold nanoparticle chemiresistors operating in biological fluids.

PubMed

Hubble, Lee J; Chow, Edith; Cooper, James S; Webster, Melissa; Müller, Karl-Heinz; Wieczorek, Lech; Raguse, Burkhard

2012-09-07

Functionalised gold nanoparticle (Au(NP)) chemiresistors are investigated for direct sensing of small organic molecules in biological fluids. The principle reason that Au(NP) chemiresistors, and many other sensing devices, have limited operation in biological fluids is due to protein and lipid fouling deactivating the sensing mechanism. In order to extend the capability of such chemiresistor sensors to operate directly in biofluids, it is essential to minimise undesirable matrix effects due to protein and lipidic components. Ultrafiltration membranes were investigated as semi-permeable size-selective barriers to prevent large biomolecule interactions with Au(NP) chemiresistors operating in protein-loaded biofluids. All of the ultrafiltration membranes protected the Au(NP) chemiresistors from fouling by the globular biomolecules, with the 10 kDa molecular weight cut-off size being optimum for operation in biofluids. Titrations of toluene in different protein-loaded fluids indicated that small molecule detection was possible. A sensor array consisting of six different thiolate-functionalised Au(NP) chemiresistors protected with a size-selective ultrafiltration membrane successfully identified, and discriminated the spoilage of pasteurised bovine milk. This proof-of-principle study demonstrates the on-chip protein separation and small metabolite detection capability, illustrating the potential for this technology in the field of microbial metabolomics. Overall, these results demonstrate that a sensor array can be protected from protein fouling with the use of a membrane, significantly increasing the possible application areas of Au(NP) chemiresistors ranging from the food industry to health services.

Frequency-dependent variation in mimetic fidelity in an intraspecific mimicry system

PubMed Central

Iserbyt, Arne; Bots, Jessica; Van Dongen, Stefan; Ting, Janice J.; Van Gossum, Hans; Sherratt, Thomas N.

2011-01-01

Contemporary theory predicts that the degree of mimetic similarity of mimics towards their model should increase as the mimic/model ratio increases. Thus, when the mimic/model ratio is high, then the mimic has to resemble the model very closely to still gain protection from the signal receiver. To date, empirical evidence of this effect is limited to a single example where mimicry occurs between species. Here, for the first time, we test whether mimetic fidelity varies with mimic/model ratios in an intraspecific mimicry system, in which signal receivers are the same species as the mimics and models. To this end, we studied a polymorphic damselfly with a single male phenotype and two female morphs, in which one morph resembles the male phenotype while the other does not. Phenotypic similarity of males to both female morphs was quantified using morphometric data for multiple populations with varying mimic/model ratios repeated over a 3 year period. Our results demonstrate that male-like females were overall closer in size to males than the other female morph. Furthermore, the extent of morphological similarity between male-like females and males, measured as Mahalanobis distances, was frequency-dependent in the direction predicted. Hence, this study provides direct quantitative support for the prediction that the mimetic similarity of mimics to their models increases as the mimic/model ratio increases. We suggest that the phenomenon may be widespread in a range of mimicry systems. PMID:21367784

The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle.

PubMed

Hu, Zhengyan; Zhao, Liang; Zhang, Hongyan; Zhang, Yi; Wu, Ren'an; Zou, Hanfa

2014-03-21

Proteins interacting with nanoparticles would form the protein coronas on the surface of nanoparticles in biological systems, which would critically impact the biological identities of nanoparticles and/or result in the physiological and pathological consequences. The enzymatic digestion of protein corona was the primary step to achieve the identification of protein components of the protein corona for the bottom-up proteomic approaches. In this study, the investigation on the tryptic digestion of protein corona by the immobilized trypsin on a magnetic nanoparticle was carried out for the first time. As a comparison with the usual overnight long-time digestion and the severe self-digestion of free trypsin, the on-bead digestion of protein corona by the immobilized trypsin could be accomplished within 1h, along with the significantly reduced self-digestion of trypsin and the improved reproducibility on the identification of proteins by the mass spectrometry-based proteomic approach. It showed that the number of identified bovine serum (BS) proteins on the commercial Fe3O4 nanoparticles was increased by 13% for the immobilized trypsin with 1h digestion as compared to that of using free trypsin with even overnight digestion. In addition, the on-bead digestion of using the immobilized trypsin was further applied on the identification of human plasma protein corona on the commercial Fe3O4 nanoparticles, which leads the efficient digestion of the human plasma proteins and the identification of 149 human plasma proteins corresponding to putative critical pathways and biological processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Methylidynetrisphosphonates: Promising C1 building block for the design of phosphate mimetics

PubMed Central

Romanenko, Vadim D

2013-01-01

Summary Methylidynetrisphosphonates are representatives of geminal polyphosphonates bearing three phosphonate (PO3H2) groups at the bridged carbon atom. Like well-known methylenebisphosphonates (BPs), they are characterized by a P–C–P backbone structure and are chemically stable mimetics of the endogenous metabolites, i.e., inorganic pyrophosphates (PPi). Because of its analogy to PPi and an ability to chelate metal ions, the 1,1,1-trisphosphonate structure is of great potential as a C1 building block for the design of phosphate mimetics. The purpose of this review is to present a concise summary of the state of the art in trisphosphonate chemistry with particular emphasis on the synthesis, structure, reactions, and potential medicinal applications of these compounds. PMID:23766816

A safe lithium mimetic for bipolar disorder

PubMed Central

Singh, Nisha; Halliday, Amy C.; Thomas, Justyn M.; Kuznetsova, Olga; Baldwin, Rhiannon; Woon, Esther C. Y.; Aley, Parvinder K.; Antoniadou, Ivi; Sharp, Trevor; Vasudevan, Sridhar R.; Churchill, Grant C.

2012-01-01

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, lithium’s therapeutic target remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebselen inhibits inositol monophosphatase and induces lithium-like effects on mouse behaviour, which are reversed with inositol, consistent with a mechanism involving inhibition of inositol recycling. Ebselen is part of the National Institutes of Health Clinical Collection, a chemical library of bioavailable drugs considered clinically safe but without proven use. Therefore, ebselen represents a lithium mimetic with the potential both to validate inositol monophosphatase inhibition as a treatment for bipolar disorder and to serve as a treatment itself. PMID:23299882

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

PubMed Central

Nair K, Lekha; Jagadeeshan, Sankar; Nair, S Asha; Kumar, GS Vinod

2011-01-01

Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release

A biosensor system using nickel ferrite nanoparticles

NASA Astrophysics Data System (ADS)

Singh, Prachi; Rathore, Deepshikha

2016-05-01

NiFe2O4 ferrite nanoparticles were synthesized by chemical co-precipitation method and the structural characteristics were investigated using X-ray diffraction technique, where single cubic phase formation of nanoparticles was confirmed. The average particle size of NiFe2O4 was found to be 4.9 nm. Nanoscale magnetic materials are an important source of labels for biosensing due to their strong magnetic properties which are not found in biological systems. This property of the material was exploited and the fabrication of the NiFe2O4 nanoparticle based biosensor was done in the form of a capacitor system, with NiFe2O4 as the dielectric material. The biosensor system was tested towards different biological materials with the help of electrochemical workstation and the same was analysed through Cole-Cole plot of NiFe2O4. The performance of the sensor was determined based on its sensitivity, response time and recovery time.

Imaging of Biological Cells Using Luminescent Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Kravets, Vira; Almemar, Zamavang; Jiang, Ke; Culhane, Kyle; Machado, Rosa; Hagen, Guy; Kotko, Andriy; Dmytruk, Igor; Spendier, Kathrin; Pinchuk, Anatoliy

2016-01-01

The application of luminescent silver nanoparticles as imaging agents for neural stem and rat basophilic leukemia cells was demonstrated. The experimental size dependence of the extinction and emission spectra for silver nanoparticles were also studied. The nanoparticles were functionalized with fluorescent glycine dimers. Spectral position of the resonance extinction and photoluminescence emission for particles with average diameters ranging from 9 to 32 nm were examined. As the particle size increased, the spectral peaks for both extinction and the intrinsic emission of silver nanoparticles shifted to the red end of the spectrum. The intrinsic photoluminescence of the particles was orders of magnitude weaker and was spectrally separated from the photoluminescence of the glycine dimer ligands. The spectral position of the ligand emission was independent of the particle size; however, the quantum yield of the nanoparticle-ligand system was size-dependent. This was attributed to the enhancement of the ligand's emission caused by the local electric field strength's dependence on the particle size. The maximum quantum yield determined for the nanoparticle-ligand complex was (5.2 ± 0.1) %. The nanoparticles were able to penetrate cell membranes of rat basophilic leukemia and neural stem cells fixed with paraformaldehyde. Additionally, toxicity studies were performed. It was found that towards rat basophilic leukemia cells, luminescent silver nanoparticles had a toxic effect in the silver atom concentration range of 10-100 μM.

In-situ formation of nanoparticles within a silicon-based matrix

DOEpatents

Thoma, Steven G [Albuquerque, NM; Wilcoxon, Jess P [Albuquerque, NM; Abrams, Billie L [Albuquerque, NM

2008-06-10

A method for encapsulating nanoparticles with an encapsulating matrix that minimizes aggregation and maintains favorable properties of the nanoparticles. The matrix comprises silicon-based network-forming compounds such as ormosils and polysiloxanes. The nanoparticles are synthesized from precursors directly within the silicon-based matrix.

Recent advancements in nanoparticle based drug delivery for gastrointestinal disorders.

PubMed

Mittal, Rahul; Patel, Amit P; Jhaveri, Vasanti M; Kay, Sae-In S; Debs, Luca H; Parrish, James M; Pan, Debbie R; Nguyen, Desiree; Mittal, Jeenu; Jayant, Rahul Dev

2018-03-01

The emergent field of nanoparticles has presented a wealth of opportunities for improving the treatment of human diseases. Recent advances have allowed for promising developments in drug delivery, diagnostics, and therapeutics. Modified delivery systems allow improved drug delivery over traditional pH, microbe, or receptor dependent models, while antibody association allows for more advanced imaging modalities. Nanoparticles have potential clinical application in the field of gastroenterology as they offer several advantages compared to the conventional treatment systems including target drug delivery, enhanced treatment efficacy, and reduced side effects. Areas covered: The aim of this review article is to summarize the recent advancements in developing nanoparticle technologies to treat gastrointestinal diseases. We have covered the application of nanoparticles in various gastrointestinal disorders including inflammatory bowel disease and colorectal cancer. We also have discussed how the gut microbiota affects the nanoparticle based drug delivery in the gastrointestinal tract. Expert opinion: Nanoparticles based drug delivery offers a great platform for targeted drug delivery for gastrointestinal disorders. However, it is influenced by the presence of microbiota, drug interaction with nanoparticles, and cytotoxicity of nanoparticles. With the advancements in nanoparticle technology, it may be possible to overcome these barriers leading to efficient drug delivery for gastrointestinal disorders based on nanoparticle platform.

The Role of BH3-Mimetic Drugs in the Treatment of Pediatric Hepatoblastoma

PubMed Central

Lieber, Justus; Armeanu-Ebinger, Sorin; Fuchs, Jörg

2015-01-01

Pediatric hepatoblastoma (HB) is commonly treated by neoadjuvant chemotherapy and surgical tumor resection according to international multicenter trial protocols. Complete tumor resection is essential and survival rates up to 95% have now been achieved in those tumors classified as standard-risk HB. Drug resistance and occurrence of metastases remain the major challenges in the treatment of HB, especially in high-risk tumors. These conditions urgently require the development of alternative therapeutic strategies. One of those alternatives is the modulation of apoptosis in HB cells. HBs regularly overexpress anti-apoptotic proteins of the Bcl-family in comparison to healthy liver tissue. This fact may contribute to the development of chemoresistance of HB cells. Synthetic small inhibitory molecules with BH3-mimetic effects, such as ABT-737 and obatoclax, enhance the susceptibility of tumor cells to different cytotoxic drugs and thereby affect initiator proteins of the apoptosis cascade via the intrinsic pathway. Besides additive effects on HB cell viability when used in combination with cytotoxic drugs, BH3-mimetics also play a role in preventing metastasation by reducing adhesion and inhibiting cell migration abilities. Presumably, including additive BH3-mimetic drugs into existing therapeutic regimens in HB patients might allow dose reduction of established cytotoxic drugs and thereby associated immanent side effects, while maintaining the antitumor activity. Furthermore, reduction of tumor growth and inhibition of tumor cell dissemination may facilitate complete surgical tumor resection, which is mandatory in this tumor type resulting in improved survival rates in high-risk HB. Currently, there are phase I and phase II clinical trials in several cancer entities using this potential target. This paper reviews the available literature regarding the use of BH3-mimetic drugs as single agents or in combination with chemotherapy in various malignancies and focuses on

Interaction of Inorganic Nanoparticles With Cell Membranes

DTIC Science & Technology

2008-10-20

the field of colloidal and biological behaviour of nanoparticles. Questions regarding the colloidal behavior of particles in biological liquids...better the behaviour of nanoparticles in living systems. 2. Research work During the preparation phase of this project we have defined following...unique knowledge of the participating researgroups in the field of colloidal and biological behaviour of nanoparticles. Questions regarding the

Biological Fate of Fe3O4 Core-Shell Mesoporous Silica Nanoparticles Depending on Particle Surface Chemistry

PubMed Central

Rascol, Estelle; Daurat, Morgane; Da Silva, Afitz; Maynadier, Marie; Dorandeu, Christophe; Charnay, Clarence; Garcia, Marcel; Lai-Kee-Him, Joséphine; Bron, Patrick; Auffan, Mélanie; Angeletti, Bernard; Devoisselle, Jean-Marie; Guari, Yannick; Gary-Bobo, Magali; Chopineau, Joël

2017-01-01

The biological fate of nanoparticles (NPs) for biomedical applications is highly dependent of their size and charge, their aggregation state and their surface chemistry. The chemical composition of the NPs surface influences their stability in biological fluids, their interaction with proteins, and their attraction to the cell membranes. In this work, core-shell magnetic mesoporous silica nanoparticles (Fe3O4@MSN), that are considered as potential theranostic candidates, are coated with polyethylene glycol (PEG) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. Their biological fate is studied in comparison to the native NPs. The physicochemical properties of these three types of NPs and their suspension behavior in different media are investigated. The attraction to a membrane model is also evaluated using a supported lipid bilayer. The surface composition of NPs strongly influences their dispersion in biological fluids mimics, protein binding and their interaction with cell membrane. While none of these types of NPs is found to be toxic on mice four days after intravenous injection of a dose of 40 mg kg−1 of NPs, their surface coating nature influences the in vivo biodistribution. Importantly, NP coated with DMPC exhibit a strong accumulation in liver and a very low accumulation in lung in comparison with nude or PEG ones. PMID:28665317

A story told by a single nanoparticle in the body fluid: demonstration of dissolution-reprecipitation of nanocrystals in a biological system.

PubMed

Wu, Cheng-Yeu; Young, David; Martel, Jan; Young, John D

2015-01-01

Analysis of the chemical composition of mineral particles found in the body is critical to understand the formation and effects of these entities in vivo. Yet, the possibility that biological fluids may modulate particle composition over time has not been examined. Materials & methods: Mineralo-organic nanoparticles similar to the ones that spontaneously form in human tissues were analyzed using electron microscopy, spectroscopy and proteomic analyses.   We show that the mineralo-organic nanoparticles assimilate various ions and minerals during incubation in ionic solutions simulating body fluids. The particles undergo dissolution-reprecipitation reactions that affect the final protein composition of the particles. The reactions occurring at the mineral-water interface therefore modulate the ionic and organic composition of mineral nanoparticles formed in biological fluids, producing changes that may alter the effects of mineral particles and stones in vivo.

Iron oxide magnetic nanoparticles with versatile surface functions based on dopamine anchors

NASA Astrophysics Data System (ADS)

Mazur, Mykola; Barras, Alexandre; Kuncser, Victor; Galatanu, Andrei; Zaitzev, Vladimir; Turcheniuk, Kostiantyn V.; Woisel, Patrice; Lyskawa, Joel; Laure, William; Siriwardena, Aloysius; Boukherroub, Rabah; Szunerits, Sabine

2013-03-01

The synthesis of multifunctional magnetic nanoparticles (MF-MPs) is one of the most active research areas in advanced materials as their multifunctional surfaces allow conjugation of biological and chemical molecules, thus making it possible to achieve target-specific diagnostic in parallel to therapeutics. We report here a simple strategy to integrate in a one-step reaction several reactive sites onto the particles. The preparation of MF-MPs is based on their simultaneous modification with differently functionalized dopamine derivatives using simple solution chemistry. The formed MF-MPs show comparable magnetic properties to those of naked nanoparticles with almost unaltered particle size of around 25 nm. The different termini, amine, azide and maleimide functions, enable further functionalization of MF-MPs by the grafting-on approach. Michael addition, Cu(i) catalyzed « click » chemistry and amidation reactions are performed on the MF-MPs integrating subsequently 6-(ferrocenyl)-hexanethiol, horseradish peroxidase (HRP) and mannose.

Multifunctional platinum-based nanoparticles for biomedical applications.

PubMed

Cheng, Qinqin; Liu, Yangzhong

2017-03-01

Platinum-based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier-based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor-specific localization as well as tumor cell uptake. The introduction of stimuli-responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor-localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real-time monitoring the distribution of drug-loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum-based anticancer drugs. WIREs Nanomed Nanobiotechnol 2017, 9:e1410. doi: 10.1002/wnan.1410 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

High-Density Lipoproteins (HDL) – Nature’s Multi-Functional Nanoparticles

PubMed Central

Kuai, Rui; Li, Dan; Chen, Y. Eugene; Moon, James J.; Schwendeman, Anna

2016-01-01

High-density lipoproteins (HDL) are endogenous nanoparticles involved in the transport and metabolism of cholesterol, phospholipids, and triglycerides. HDL is well known as the ―good‖ cholesterol because it not only removes excess cholesterol from atherosclerotic plaques but also has anti-inflammatory and anti-oxidative properties, which protect the cardiovascular system. Circulating HDL also transports endogenous proteins, vitamins, hormones, and microRNA to various organs. Compared with other synthetic nanocarriers, such as liposomes, micelles, inorganic and polymeric nanoparticles, HDL has unique features that allow them to deliver cargo to specific targets more efficiently. These attributes include their ultra-small size (8-12 nm in diameter), high tolerability in humans (up to 8 g of protein per infusion), long circulating half-life (12-24 hours), and intrinsic targeting properties to different recipient cells. Various recombinant ApoA proteins and ApoA mimetic peptides have been recently developed for the preparation of reconstituted HDL that exhibits properties similar to endogenous HDL and has a potential for industrial scale-up. In this review, we will summarize: a) clinical pharmacokinetics and safety of reconstituted HDL products, b) comparison of HDL with inorganic and other organic nanoparticles, c) the rationale for using HDL as drug delivery vehicles for important therapeutic indications, d) the current state-of-the-art in HDL production, and e) HDL-based drug delivery strategies for small molecules, peptides/proteins, nucleic acids, and imaging agents targeted to various organs. PMID:26889958

Application of a Nanostructured Enzymatic Biosensor Based on Fullerene and Gold Nanoparticles to Polyphenol Detection.

PubMed

Tortolini, Cristina; Sanzò, Gabriella; Antiochia, Riccarda; Mazzei, Franco; Favero, Gabriele

2017-01-01

Electrochemical biosensors provide an attractive means of analyzing the content of a biological sample due to the direct conversion of a biological event to an electronic signal. The signal transduction and the general performance of electrochemical biosensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. We show herein a novel electrochemical biosensing platform based on the coupling of two different nanostructured materials (gold nanoparticles and fullerenols) displaying interesting electrochemical features. The use of these nanomaterials improved the electrochemical performance of the proposed biosensor.An application of the nanostructured enzyme-based biosensor has been developed for evaluating the detection of polyphenols either in buffer solution or in real wine samples.

Interaction of Colloidal Gold Nanoparticles with Model Serum Proteins: The Nanoparticle-Protein 'Corona' from a PhysicoChemical Viewpoint

NASA Astrophysics Data System (ADS)

Dominguez Medina, Sergio

When nanoparticles come in contact with biological fluids they become coated with a mixture of proteins present in the media, forming what is known as the nanoparticle-protein 'corona'. This corona changes the nanoparticles' original surface properties and plays a central role in how these get screened by cellular receptors. In the context of biomedical research, this presents a bottleneck for the transition of nanoparticles from research laboratories to clinical settings. It is therefore fundamental to probe these nanoparticle-protein interactions in order to understand the different physico-chemical mechanisms involved. This thesis is aimed to investigate the exposure of colloidal gold nanoparticles to model serum proteins, particularly serum albumin, the main transporter of molecular compounds in the bloodstream of mammals. A set of experimental tools based on optical microscopy and spectroscopy were developed in order to probe these interactions in situ. First, the intrinsic photoluminescence and elastic scattering of individual gold nanoparticles were investigated in order to understand its physical origin. These optical signals were then used to measure the size of the nanoparticles while in Brownian diffusion using fluctuation correlation spectroscopy. This spectroscopic tool was then applied to detect the binding of serum albumin onto the nanoparticle surface, increasing its hydrodynamic size. By performing a binding isotherm as a function of protein concentration, it was determined that serum albumin follows an anti-cooperative binding mechanism on negatively charged gold nanoparticles. This protein monolayer substantially enhanced the stability of the colloid, preventing their aggregation in saline solutions with ionic strength higher than biological media. Cationic gold nanoparticles in contrast, aggregated when serum albumin was present at a low protein-to-nanoparticle ratio, but prevented aggregation if exposed in excess. Single-molecule fluorescence

Microfluidic paper-based device for colorimetric determination of glucose based on a metal-organic framework acting as peroxidase mimetic.

PubMed

Ortiz-Gómez, Inmaculada; Salinas-Castillo, Alfonso; García, Amalia García; Álvarez-Bermejo, José Antonio; de Orbe-Payá, Ignacio; Rodríguez-Diéguez, Antonio; Capitán-Vallvey, Luis Fermín

2017-12-13

This work presents a microfluidic paper-based analytical device (μPAD) for glucose determination using a supported metal-organic framework (MOF) acting as a peroxidase mimic. The catalytic action of glucose oxidase (GOx) on glucose causes the formation of H 2 O 2 , and the MOF causes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H 2 O 2 to form a blue-green product with an absorption peak at 650 nm in the detection zone. A digital camera and the iOS feature of a smartphone are used for the quantitation of glucose with the S coordinate of the HSV color space as the analytical parameter. Different factors such as the concentration of TMB, GOx and MOF, pH and buffer, sample volume, reaction time and reagent position in the μPAD were optimized. Under optimal conditions, the value for the S coordinate increases linearly up to 150 μmol·L -1 glucose concentrations, with a 2.5 μmol·L -1 detection limit. The μPAD remains stable for 21 days under conventional storage conditions. Such an enzyme mimetic-based assay to glucose determination using Fe-MIL-101 MOF implemented in a microfluidic paper-based device possesses advantages over enzyme-based assays in terms of costs, durability and stability compared to other existing glucose determination methods. The procedure was applied to the determination of glucose in (spiked) serum and urine. Graphical abstract Schematic representation of microfluidic paper-based analytical device using metal-organic framework as a peroxidase mimic for colorimetric glucose detection with digital camera or smartphone and iOS app readout.

Dispersion Behaviour of Silica Nanoparticles in Biological Media and Its Influence on Cellular Uptake.

PubMed

Halamoda-Kenzaoui, Blanka; Ceridono, Mara; Colpo, Pascal; Valsesia, Andrea; Urbán, Patricia; Ojea-Jiménez, Isaac; Gioria, Sabrina; Gilliland, Douglas; Rossi, François; Kinsner-Ovaskainen, Agnieszka

2015-01-01

Given the increasing variety of manufactured nanomaterials, suitable, robust, standardized in vitro screening methods are needed to study the mechanisms by which they can interact with biological systems. The in vitro evaluation of interactions of nanoparticles (NPs) with living cells is challenging due to the complex behaviour of NPs, which may involve dissolution, aggregation, sedimentation and formation of a protein corona. These variable parameters have an influence on the surface properties and the stability of NPs in the biological environment and therefore also on the interaction of NPs with cells. We present here a study using 30 nm and 80 nm fluorescently-labelled silicon dioxide NPs (Rubipy-SiO2 NPs) to evaluate the NPs dispersion behaviour up to 48 hours in two different cellular media either supplemented with 10% of serum or in serum-free conditions. Size-dependent differences in dispersion behaviour were observed and the influence of the living cells on NPs stability and deposition was determined. Using flow cytometry and fluorescence microscopy techniques we studied the kinetics of the cellular uptake of Rubipy-SiO2 NPs by A549 and CaCo-2 cells and we found a correlation between the NPs characteristics in cell media and the amount of cellular uptake. Our results emphasize how relevant and important it is to evaluate and to monitor the size and agglomeration state of nanoparticles in the biological medium, in order to interpret correctly the results of the in vitro toxicological assays.

Dispersion Behaviour of Silica Nanoparticles in Biological Media and Its Influence on Cellular Uptake

PubMed Central

Halamoda-Kenzaoui, Blanka; Ceridono, Mara; Colpo, Pascal; Valsesia, Andrea; Urbán, Patricia; Ojea-Jiménez, Isaac; Gioria, Sabrina; Gilliland, Douglas; Rossi, François; Kinsner-Ovaskainen, Agnieszka

2015-01-01

Given the increasing variety of manufactured nanomaterials, suitable, robust, standardized in vitro screening methods are needed to study the mechanisms by which they can interact with biological systems. The in vitro evaluation of interactions of nanoparticles (NPs) with living cells is challenging due to the complex behaviour of NPs, which may involve dissolution, aggregation, sedimentation and formation of a protein corona. These variable parameters have an influence on the surface properties and the stability of NPs in the biological environment and therefore also on the interaction of NPs with cells. We present here a study using 30 nm and 80 nm fluorescently-labelled silicon dioxide NPs (Rubipy-SiO2 NPs) to evaluate the NPs dispersion behaviour up to 48 hours in two different cellular media either supplemented with 10% of serum or in serum-free conditions. Size-dependent differences in dispersion behaviour were observed and the influence of the living cells on NPs stability and deposition was determined. Using flow cytometry and fluorescence microscopy techniques we studied the kinetics of the cellular uptake of Rubipy-SiO2 NPs by A549 and CaCo-2 cells and we found a correlation between the NPs characteristics in cell media and the amount of cellular uptake. Our results emphasize how relevant and important it is to evaluate and to monitor the size and agglomeration state of nanoparticles in the biological medium, in order to interpret correctly the results of the in vitro toxicological assays. PMID:26517371

Protamine-based nanoparticles as new antigen delivery systems.

PubMed

González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

2015-11-01

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

A predictive model of iron oxide nanoparticles flocculation tuning Z-potential in aqueous environment for biological application

NASA Astrophysics Data System (ADS)

Baldassarre, Francesca; Cacciola, Matteo; Ciccarella, Giuseppe

2015-09-01

Iron oxide nanoparticles are the most used magnetic nanoparticles in biomedical and biotechnological field because of their nontoxicity respect to the other metals. The investigation of iron oxide nanoparticles behaviour in aqueous environment is important for the biological applications in terms of polydispersity, mobility, cellular uptake and response to the external magnetic field. Iron oxide nanoparticles tend to agglomerate in aqueous solutions; thus, the stabilisation and aggregation could be modified tuning the colloids physical proprieties. Surfactants or polymers are often used to avoid agglomeration and increase nanoparticles stability. We have modelled and synthesised iron oxide nanoparticles through a co-precipitation method, in order to study the influence of surfactants and coatings on the aggregation state. Thus, we compared experimental results to simulation model data. The change of Z-potential and the clusters size were determined by Dynamic Light Scattering. We developed a suitable numerical model to predict the flocculation. The effects of Volume Mean Diameter and fractal dimension were explored in the model. We obtained the trend of these parameters tuning the Z-potential. These curves matched with the experimental results and confirmed the goodness of the model. Subsequently, we exploited the model to study the influence of nanoparticles aggregation and stability by Z-potential and external magnetic field. The highest Z-potential is reached up with a small external magnetic influence, a small aggregation and then a high suspension stability. Thus, we obtained a predictive model of Iron oxide nanoparticles flocculation that will be exploited for the nanoparticles engineering and experimental setup of bioassays.

Modulation of stress-induced neurobehavioral changes and brain oxidative injury by nitric oxide (NO) mimetics in rats.

PubMed

Gulati, Kavita; Chakraborti, Ayanabha; Ray, Arunabha

2007-11-02

The present study evaluated the effects of NO mimetics on stress-induced neurobehavioral changes and the possible involvement of ROS-RNS interactions in rats. Restraint stress (RS) suppressed both percent open arm entries and time spent in the open arms in the elevated plus maze (EPM) test. These RS-induced changes in EPM activity were attenuated by the NO mimetics, l-arginine, isosorbide dinitrate and molsidomine, in a differential manner. RS-exposed rats showed (a) increased lipid peroxidation (MDA) and (b) lowered reduced glutathione (GSH) and NO metabolites (NOx), in brain homogenates of these animals. Pretreatment with the NO mimetics also differentially influenced RS-induced changes in brain oxidative stress markers. The results suggest that NO may protect against stress-induced anxiogenic behavior and oxidative injury in the brain and highlight the significance of ROS-RNS interactions.

Highly sensitive immunoassay of protein molecules based on single nanoparticle fluorescence detection in a nanowell

NASA Astrophysics Data System (ADS)

Han, Jin-Hee; Kim, Hee-Joo; Lakshmana, Sudheendra; Gee, Shirley J.; Hammock, Bruce D.; Kennedy, Ian M.

2011-03-01

A nanoarray based-single molecule detection system was developed for detecting proteins with extremely high sensitivity. The nanoarray was able to effectively trap nanoparticles conjugated with biological sample into nanowells by integrating with an electrophoretic particle entrapment system (EPES). The nanoarray/EPES is superior to other biosensor using immunoassays in terms of saving the amounts of biological solution and enhancing kinetics of antibody binding due to reduced steric hindrance from the neighboring biological molecules. The nanoarray patterned onto a layer of PMMA and LOL on conductive and transparent indium tin oxide (ITO)-glass slide by using e-beam lithography. The suspension of 500 nm-fluorescent (green emission)-carboxylated polystyrene (PS) particles coated with protein-A followed by BDE 47 polyclonal antibody was added to the chip that was connected to the positive voltage. The droplet was covered by another ITO-coated-glass slide and connected to a ground terminal. After trapping the particles into the nanowells, the solution of different concentrations of anti-rabbit- IgG labeled with Alexa 532 was added for an immunoassay. A single molecule detection system could quantify the anti-rabbit IgG down to atto-mole level by counting photons emitted from the fluorescent dye bound to a single nanoparticle in a nanowell.

Mimetic Ag nanoparticle/Zn-based MOF nanocomposite (AgNPs@ZnMOF) capped with molecularly imprinted polymer for the selective detection of patulin.

PubMed

Bagheri, Nafiseh; Khataee, Alireza; Habibi, Biuck; Hassanzadeh, Javad

2018-03-01

Here, Ag nanoparticle/flake-like Zn-based MOF nanocomposite (AgNPs@ZnMOF) with great peroxidase-like activity was applied as an efficient support for molecularly imprinted polymer (MIP) and successfully used for selective determination of patulin. AgNPs@ZnMOF was simply synthesized by creating Ag nanoparticles (Ag NPs) inside the nano-pores of flake-like (Zn)MOF. The high surface area of MOF remarkably improved the catalytic activity of Ag NPs which was assessed by fluorometric, colorimetric and electrochemical techniques. Furthermore, it was observed that patulin could strangely reduce the catalytic activity of AgNPs@ZnMOF, probably due to its electron capturing features. This outcome was the motivation to design an assay for patulin detection. In order to make a selective interaction with patulin molecules, MIP layer was created on the surface of AgNPs@ZnMOF by co-polymerization reaction of 3-aminopropyl triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) monomers wherein patulin was applied as template agent. Combination between the selective identifying feature of MIP and outstanding peroxidase-like activity of novel AgNPs@ZnMOF nanocomposite as well as the sensitive fluorescence detection system was led to the design of a reliable probe for patulin. The prepared MIP-capped AgNPs@ZnMOF catalyzed the H 2 O 2 -terephthalic acid reaction which produced a high florescent product. In the presence of patulin, the fluorescence intensity was decreased proportional to its concentration in the range of 0.1-10µmolL -1 with a detection limit of 0.06µmolL -1 . The proposed method was able to selectively measure patulin in a complex media without significant interfering effects from analogue compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of particle size on the toxic action of silver nanoparticles

NASA Astrophysics Data System (ADS)

Sosenkova, L. S.; Egorova, E. M.

2011-04-01

Silver nanoparticles in AOT reverse micelles were obtained by means of the biochemical synthesis. Synthesis of nanoparticles was carried out with variation of the three parameters of reverse-micellar systems: concentration of silver ions, concentration of the stabilizer (AOT) and hydration extent w = [H2O]/[AOT]. The combinations of varied parameters have been found, allowing to prepare micellar solutions of spherical silver nanoparticles with average sizes 4.6 and 9.5 nm and narrow size distribution. From micellar solution the nanoparticles were transferred into the water phase; water solutions of the nanoparticles were used for testing their biological activity. Our assay is based on negative chemotaxis, a motile reaction of cells to an unfavorable chemical environment. Plasmodium of the slime mold Physarum polycephalum used as an object is a multinuclear amoeboid cell with unlimited growth and the auto-oscillatory mode of locomotion. In researches of chemotaxis on plasmodium it is learned that silver nanoparticles of smaller size exhibit a higher biological activity (behave as stronger repellent) and this correlates with the literary data obtained in studies of silver nanoparticles interaction with other biological objects.

Enhancing regenerative approaches with nanoparticles

PubMed Central

Habibovic, Pamela

2017-01-01

In this review, we discuss recent developments in the field of nanoparticles and their use in tissue regeneration approaches. Owing to their unique chemical properties and flexibility in design, nanoparticles can be used as drug delivery systems, to create novel features within materials or as bioimaging agents, or indeed these properties can be combined to create smart multifunctional structures. This review aims to provide an overview of this research field where the focus will be on nanoparticle-based strategies to stimulate bone regeneration; however, the same principles can be applied for other tissue and organ regeneration strategies. In the first section, nanoparticle-based methods for the delivery of drugs, growth factors and genetic material to promote tissue regeneration are discussed. The second section deals with the addition of nanoparticles to materials to create nanocomposites. Such materials can improve several material properties, including mechanical stability, biocompatibility and biological activity. The third section will deal with the emergence of a relatively new field of research using nanoparticles in advanced cell imaging and stem cell tracking approaches. As the development of nanoparticles continues, incorporation of this technology in the field of regenerative medicine will ultimately lead to new tools that can diagnose, track and stimulate the growth of new tissues and organs. PMID:28404870

Enhancing regenerative approaches with nanoparticles.

PubMed

van Rijt, Sabine; Habibovic, Pamela

2017-04-01

In this review, we discuss recent developments in the field of nanoparticles and their use in tissue regeneration approaches. Owing to their unique chemical properties and flexibility in design, nanoparticles can be used as drug delivery systems, to create novel features within materials or as bioimaging agents, or indeed these properties can be combined to create smart multifunctional structures. This review aims to provide an overview of this research field where the focus will be on nanoparticle-based strategies to stimulate bone regeneration; however, the same principles can be applied for other tissue and organ regeneration strategies. In the first section, nanoparticle-based methods for the delivery of drugs, growth factors and genetic material to promote tissue regeneration are discussed. The second section deals with the addition of nanoparticles to materials to create nanocomposites. Such materials can improve several material properties, including mechanical stability, biocompatibility and biological activity. The third section will deal with the emergence of a relatively new field of research using nanoparticles in advanced cell imaging and stem cell tracking approaches. As the development of nanoparticles continues, incorporation of this technology in the field of regenerative medicine will ultimately lead to new tools that can diagnose, track and stimulate the growth of new tissues and organs. © 2017 The Author(s).

Molecular building kit of fused-proline-derived peptide mimetics allowing specific adjustment of the dihedral Psi angle.

PubMed

Einsiedel, Juergen; Lanig, Harald; Waibel, Reiner; Gmeiner, Peter

2007-11-23

Proline-derived peptide mimetics have become an area of paramount importance in peptide and protein chemistry. Since protein crystal structures frequently display Psi angles of 140-170 degrees for prolyl moieties, our intention was to design a completely novel series of 2,3-fused-proline-derived lactams covering this particular conformational space. Extending our recently described toolset of spirocyclic reverse-turn mimetics, we synthesized pyrrolidinyl-fused seven-, eight-, and nine-membered unsaturated lactam model peptides taking advantage of Grubbs' ring-closing metathesis. Investigating the seven-membered lactam 3a by means of IR and NMR spectroscopy and semiempirical molecular dynamics simulations, we could not observe a U-turn conformation; however, increasing the ring size to give eight- and nine-membered congeners revealed moderate and high type IotaIota beta-turn inducing properties. Interestingly, the conformational properties of our model systems depend on both the ring size of the fused dehydro-Freidinger lactam and the position of the endocyclic double bond. Superior reverse-turn inducing properties could be observed for the fused azacyclononenone 3e. According to diagnostic transanular NOEs, a discrete folding principle of the lactam ring strongly deviating from the regioisomeric lactams 3c,f explains the conformational behavior. Hence, we were able to establish a molecular building kit that allows adjustments of a wide range of naturally occurring proline Psi angles and thus can be exploited to probe molecular recognition and functional properties of biological systems.

Task-based exposure assessment of nanoparticles in the workplace

NASA Astrophysics Data System (ADS)

Ham, Seunghon; Yoon, Chungsik; Lee, Euiseung; Lee, Kiyoung; Park, Donguk; Chung, Eunkyo; Kim, Pilje; Lee, Byoungcheun

2012-09-01

Although task-based sampling is, theoretically, a plausible approach to the assessment of nanoparticle exposure, few studies using this type of sampling have been published. This study characterized and compared task-based nanoparticle exposure profiles for engineered nanoparticle manufacturing workplaces (ENMW) and workplaces that generated welding fumes containing incidental nanoparticles. Two ENMW and two welding workplaces were selected for exposure assessments. Real-time devices were utilized to characterize the concentration profiles and size distributions of airborne nanoparticles. Filter-based sampling was performed to measure time-weighted average (TWA) concentrations, and off-line analysis was performed using an electron microscope. Workplace tasks were recorded by researchers to determine the concentration profiles associated with particular tasks/events. This study demonstrated that exposure profiles differ greatly in terms of concentrations and size distributions according to the task performed. The size distributions recorded during tasks were different from both those recorded during periods with no activity and from the background. The airborne concentration profiles of the nanoparticles varied according to not only the type of workplace but also the concentration metrics. The concentrations measured by surface area and the number concentrations measured by condensation particle counter, particulate matter 1.0, and TWA mass concentrations all showed a similar pattern, whereas the number concentrations measured by scanning mobility particle sizer indicated that the welding fume concentrations at one of the welding workplaces were unexpectedly higher than were those at workplaces that were engineering nanoparticles. This study suggests that a task-based exposure assessment can provide useful information regarding the exposure profiles of nanoparticles and can therefore be used as an exposure assessment tool.

Chitosan-based nanoparticles for improving immunization against hepatitis B infection.

PubMed

Prego, Cecilia; Paolicelli, Patrizia; Díaz, Belen; Vicente, Sara; Sánchez, Alejandro; González-Fernández, Africa; Alonso, María José

2010-03-19

The design of effective vaccine delivery vehicles is opening up new possibilities for making immunization more equitable, safe and efficient. In this work, we purpose polysaccharidic-based nanoparticles as delivery structures for virus-like particle antigens, using recombinant hepatitis B surface antigen (rHBsAg) as a model. Polysaccharidic-based nanoparticles were prepared using a very mild ionic gelation technique, by cross-linking the polysaccharide chitosan (CS) with a counter ion. The resulting nanoparticles could be easily isolated with a size in the nanometric range (160-200 nm) and positive surface charge (+6 to +10 mV). More importantly, CS-based nanoparticles allowed the efficient association of the antigen (>60%) while maintaining the antigenic epitope intact, as determined by ELISA and Western blot. The entrapped antigen was further released in vitro from the nanoparticles in a sustained manner without compromising its antigenicity. In addition, loaded CS-based nanoparticles were stable, and protected the associated antigen during storage, either as an aqueous suspension under different temperature conditions (+4 degrees C and -20 degrees C), or as a dried form after freeze-drying the nanoparticles. Finally, immunization studies showed the induction of important seroprotection rates after intramuscular administration of the nanoparticles, indicating their adjuvant capacity. In fact, CS-based nanoparticles were able to induce anti-HBsAg IgG levels up to 5500 mIU/ml, values 9-fold the conventional alum-adsorbed vaccine. In conclusion, we report here a polysaccharidic nanocarrier which exhibits a number of in vitro and in vivo features that make it a promising adjuvant for vaccine delivery of subunit antigens. Copyright 2010 Elsevier Ltd. All rights reserved.

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

PubMed Central

Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

Estimation of sensing characteristics for refractory nitrides based gain assisted core-shell plasmonic nanoparticles

NASA Astrophysics Data System (ADS)

Shishodia, Manmohan Singh; Pathania, Pankaj

2018-04-01

Refractory transition metal nitrides such as zirconium nitride (ZrN), hafnium nitride (HfN) and titanium nitride (TiN) have emerged as viable alternatives to coinage metals based plasmonic materials, e.g., gold (Au) and silver (Ag). The present work assesses the suitability of gain assisted ZrN-, HfN- and TiN-based conventional core-shell nanoparticles (CCSNPs) and multilayered core-shell nanoparticles (MCSNPs) for refractive index sensing. We report that the optical gain incorporation in the dielectric layer leads to multifold enhancement of the scattering efficiency (Qsca), substantial reduction of the spectral full width at half maximum, and a higher figure of merit (FOM). In comparison with CCSNPs, the MCSNP system exhibits superior sensing characteristics such as higher FOM, ˜ 45% reduction in the critical optical gain, response shift towards the biological window, and higher degree of tunability. Inherent biocompatibility, growth compatibility, chemical stability and flexible spectral tuning of refractory nitrides augmented by superior sensing properties in the present work may pave the way for refractory nitrides based low cost sensing.

Si-based Nanoparticles: a biocompatibility study

NASA Astrophysics Data System (ADS)

Rivolta, I.; Lettiero, B.; Panariti, A.; D'Amato, R.; Maurice, V.; Falconieri, M.; Herlein, N.; Borsella, E.; Miserocchi, G.

2010-10-01

Exposure to silicon nanoparticles (Si-NPs) may occur in professional working conditions or for people undergoing a diagnostic screening test. Despite the fact that silicon is known as a non-toxic material, in the first case the risk is mostly related to the inhalation of nanoparticles, thus the most likely route of entry is across the lung alveolar epithelium. In the case of diagnostic imaging, nanoparticles are usually injected intravenously and Si-NPs could impact on the endothelial wall. In our study we investigated the interaction between selected Si-based NPs and an epithelial lung cell line. Our data showed that, despite the overall silicon biocompatibility, however accurate studies of the potential toxicity induced by the nanostructure and engineered surface characteristics need to be accurately investigated before Si nanoparticles can be safely used for in vivo applications as bio-imaging, cell staining and drug delivery.

Recent Advances on Inorganic Nanoparticle-Based Cancer Therapeutic Agents

PubMed Central

Wang, Fenglin; Li, Chengyao; Cheng, Jing; Yuan, Zhiqin

2016-01-01

Inorganic nanoparticles have been widely investigated as therapeutic agents for cancer treatments in biomedical fields due to their unique physical/chemical properties, versatile synthetic strategies, easy surface functionalization and excellent biocompatibility. This review focuses on the discussion of several types of inorganic nanoparticle-based cancer therapeutic agents, including gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and mesoporous silica nanoparticles. Several cancer therapy techniques are briefly introduced at the beginning. Emphasis is placed on how these inorganic nanoparticles can provide enhanced therapeutic efficacy in cancer treatment through site-specific accumulation, targeted drug delivery and stimulated drug release, with elaborations on several examples to highlight the respective strategies adopted. Finally, a brief summary and future challenges are included. PMID:27898016

Recent Advances on Inorganic Nanoparticle-Based Cancer Therapeutic Agents.

PubMed

Wang, Fenglin; Li, Chengyao; Cheng, Jing; Yuan, Zhiqin

2016-11-25

Inorganic nanoparticles have been widely investigated as therapeutic agents for cancer treatments in biomedical fields due to their unique physical/chemical properties, versatile synthetic strategies, easy surface functionalization and excellent biocompatibility. This review focuses on the discussion of several types of inorganic nanoparticle-based cancer therapeutic agents, including gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and mesoporous silica nanoparticles. Several cancer therapy techniques are briefly introduced at the beginning. Emphasis is placed on how these inorganic nanoparticles can provide enhanced therapeutic efficacy in cancer treatment through site-specific accumulation, targeted drug delivery and stimulated drug release, with elaborations on several examples to highlight the respective strategies adopted. Finally, a brief summary and future challenges are included.

Low-cost endoscopic third ventriculostomy simulator with mimetic endoscope.

PubMed

Garling, Richard Justin; Jin, Xin; Yang, Jianzhong; Khasawneh, Ahmad H; Harris, Carolyn Anne

2018-05-11

OBJECTIVE Hydrocephalus affects approximately 1 in 500 people in the US, yet ventricular shunting, the gold standard of treatment, has a nearly 85% failure rate. Endoscopic third ventriculostomy (ETV) is an alternative surgical approach for a specific subset of hydrocephalic patients, but can be limited by the inability of neurosurgical residents to practice prior to patient contact. The goal of this study was to create an affordable ETV model and endoscope for resident training. METHODS Open-source software was used to isolate the skull and brain from the CT and MR images of a 2-year-old boy with hydrocephalus. A 3D printer created the skull and a 3D mold of the brain. A mixture of silicone and silicone tactile mutator was used to cast the brain mold prior to subsequent compression and shearing modulus testing. A mimetic endoscope was then created from basic supplies and a 3D printed frame. A small cohort of neurosurgical residents and attending physicians evaluated the ETV simulator with mimetic endoscope. RESULTS The authors successfully created a mimetic endoscope and ETV simulator. After compression and shearing modulus testing, a silicone/Slacker ratio between 10:6 and 10:7 was found to be similar to that of human brain parenchyma. Eighty-seven percent of participants strongly agreed that the simulator was useful for resident training, and 93% strongly agreed that the simulator helped them understand how to orient themselves with the endoscope. CONCLUSIONS The authors created an affordable (US$123, excluding 3D printer), easy-to-use ETV simulator with endoscope. Previous models have required expensive software and costly operative endoscopes that may not be available to most residents. Instead, this attempt takes advantage of open-source software for the manipulation and fabrication of a patient-specific mold. This model can assist with resident development, allowing them to safely practice use of the endoscope in ETV.

Recent advances and future prospects of iron oxide nanoparticles in biomedicine and diagnostics.

PubMed

Vallabani, N V Srikanth; Singh, Sanjay

2018-06-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are considered as chemically inert materials and, therefore, being extensively applied in the areas of imaging, targeting, drug delivery and biosensors. Their unique properties such as low toxicity, biocompatibility, potent magnetic and catalytic behavior and superior role in multifunctional modalities have epitomized them as an appropriate candidate for biomedical applications. Recent developments in the area of materials science have enabled the facile synthesis of Iron oxide nanoparticles (IONPs) offering easy tuning of surface properties and surface functionalization with desired biomolecules. Such developments have enabled IONPs to be easily accommodated in nanocomposite platform or devices. Additionally, the tag of biocompatible material has realized their potential in myriad applications of nanomedicines including imaging modalities, sensing, and therapeutics. Further, IONPs enzyme mimetic activity pronounced their role as nanozymes in detecting biomolecules like glucose, and cholesterol etc. Hence, based on their versatile applications in biomedicine, the present review article focusses on the current trends, developments and future prospects of IONPs in MRI, hyperthermia, photothermal therapy, biomolecules detection, chemotherapy, antimicrobial activity and also their role as the multifunctional agent in diagnosis and nanomedicines.

Colorimetric assay of heparin in plasma based on the inhibition of oxidase-like activity of citrate-capped platinum nanoparticles.

PubMed

You, Jyun-Guo; Liu, Yao-Wen; Lu, Chi-Yu; Tseng, Wei-Lung; Yu, Cheng-Ju

2017-06-15

We report citrate-capped platinum nanoparticles (Pt NPs) as oxidase mimetics for effectively catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), dopamine, and methylene blue in the presence of O 2 . To confirm oxidase-like activity of citrate-capped Pt NPs, their activity toward oxygen reduction reaction was studied using cyclic voltammetry and rotating ring-disk electrode method. The results obtained showed that Pt NP NPs can catalyze the oxidation of organic substrates to the colored product and the reduction of oxygen to water through a four-electron exchange process. Because the aggregation of Pt NPs can inhibit their oxidase-like activity and protamine can recognize heparin, we prepared the protamine-modified Pt NPs through direct adsorption on the surface of citrate-capped Pt NPs. The electrostatic attraction between heparin and protamine-stabilized Pt NPs induced nanoparticle aggregation, inhibiting their catalytic activity. Therefore, the lowest detectable heparin concentrations through UV-vis absorption and by the naked eye were estimated to be 0.3 and 60nM, respectively. Moreover, the proposed system enabled the determination of the therapeutic heparin concentration in a single drop of blood. Copyright © 2016 Elsevier B.V. All rights reserved.

Grafting of allylimidazole and n-vinylcaprolactam as a thermosensitive polymer onto magnetic nano-particles for the extraction and determination of celecoxib in biological samples.

PubMed

Morovati, Atefeh; Ahmad Panahi, Homayon; Yazdani, Farzaneh

2016-11-20

In this research, a novel method is reported for the surface grafting of n-vinylcaprolactam as a thermosensitive agent and allylimidazole with affinity toward celecoxib onto magnetic nano-particles. The grafted nano-particles were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The surface morphology was studied using Scanning Electron Microscopy. The resulting grafted nano-particles were used for the determination of trace celecoxib in biological human fluids and pharmaceutical samples. The profile of celecoxib uptake by the modified magnetic nano-particles indicated good accessibility of the active sites in the grafted copolymer. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. Solid phase extraction for biological fluids such as urine and serum were investigated. In this study, urine extraction recovery of more than 95% was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanobiotechnology today: focus on nanoparticles.

PubMed

Soloviev, Mikhail

2007-12-30

In the recent years the nanobiotechnology field and the Journal of Nanobiotechnology readership have witnessed an increase in interest towards the nanoparticles and their biological effects and applications. These include bottom-up and molecular self-assembly, biological effects of naked nanoparticles and nano-safety, drug encapsulation and nanotherapeutics, and novel nanoparticles for use in microscopy, imaging and diagnostics. This review highlights recent Journal of Nanobiotechnology publications in some of these areas http://www.jnanobiotechnology.com.

Nanobiotechnology today: focus on nanoparticles

PubMed Central

Soloviev, Mikhail

2007-01-01

In the recent years the nanobiotechnology field and the Journal of Nanobiotechnology readership have witnessed an increase in interest towards the nanoparticles and their biological effects and applications. These include bottom-up and molecular self-assembly, biological effects of naked nanoparticles and nano-safety, drug encapsulation and nanotherapeutics, and novel nanoparticles for use in microscopy, imaging and diagnostics. This review highlights recent Journal of Nanobiotechnology publications in some of these areas . PMID:18163916

Structurally homogeneous nanosheets from self-assembly of a collagen-mimetic peptide.

PubMed

Jiang, Tao; Xu, Chunfu; Zuo, Xiaobing; Conticello, Vincent P

2014-08-04

A collagen-mimetic peptide, NSIII, has been designed with three sequential blocks having positive, neutral, and negative charges, respectively. The non-canonical imino acid, (2S,4S)-4-aminoproline (amp), was used to specify the positive charges at the Xaa positions of (Xaa-Yaa-Gly) triads in the N-terminal domain of NSIII. Peptide NSIII underwent self-assembly from aqueous solution to form a highly homogeneous population of nanosheets. Two-dimensional crystalline sheets formed in which the length of the peptide defined the height of the sheets. These results contrasted with prior results on a similar multi-domain collagen-mimetic polypeptides in which the sheets had highly polydisperse distribution of sizes in the (x/y)- and (z)-dimensions. The structural differences between the two nanosheet assemblies were interpreted in terms of the relative stereoelectronic effects of the different aminoproline derivatives on the local triple helical conformation of the peptides. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

WO3 nanoparticle-based conformable pH sensor.

PubMed

Santos, Lídia; Neto, Joana P; Crespo, Ana; Nunes, Daniela; Costa, Nuno; Fonseca, Isabel M; Barquinha, Pedro; Pereira, Luís; Silva, Jorge; Martins, Rodrigo; Fortunato, Elvira

2014-08-13

pH is a vital physiological parameter that can be used for disease diagnosis and treatment as well as in monitoring other biological processes. Metal/metal oxide based pH sensors have several advantages regarding their reliability, miniaturization, and cost-effectiveness, which are critical characteristics for in vivo applications. In this work, WO3 nanoparticles were electrodeposited on flexible substrates over metal electrodes with a sensing area of 1 mm(2). These sensors show a sensitivity of -56.7 ± 1.3 mV/pH, in a wide pH range of 9 to 5. A proof of concept is also demonstrated using a flexible reference electrode in solid electrolyte with a curved surface. A good balance between the performance parameters (sensitivity), the production costs, and simplicity of the sensors was accomplished, as required for wearable biomedical devices.

A review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: A green expertise

PubMed Central

Ahmed, Shakeel; Ahmad, Mudasir; Swami, Babu Lal; Ikram, Saiqa

2015-01-01

Metallic nanoparticles are being utilized in every phase of science along with engineering including medical fields and are still charming the scientists to explore new dimensions for their respective worth which is generally attributed to their corresponding small sizes. The up-and-coming researches have proven their antimicrobial significance. Among several noble metal nanoparticles, silver nanoparticles have attained a special focus. Conventionally silver nanoparticles are synthesized by chemical method using chemicals as reducing agents which later on become accountable for various biological risks due to their general toxicity; engendering the serious concern to develop environment friendly processes. Thus, to solve the objective; biological approaches are coming up to fill the void; for instance green syntheses using biological molecules derived from plant sources in the form of extracts exhibiting superiority over chemical and/or biological methods. These plant based biological molecules undergo highly controlled assembly for making them suitable for the metal nanoparticle syntheses. The present review explores the huge plant diversity to be utilized towards rapid and single step protocol preparatory method with green principles over the conventional ones and describes the antimicrobial activities of silver nanoparticles. PMID:26843966

3D nanometer images of biological fibers by directed motion of gold nanoparticles.

PubMed

Estrada, Laura C; Gratton, Enrico

2011-11-09

Using near-infrared femtosecond pulses, we move single gold nanoparticles (AuNPs) along biological fibers, such as collagen and actin filaments. While the AuNP is sliding on the fiber, its trajectory is measured in three dimensions (3D) with nanometer resolution providing a high-resolution image of the fiber. Here, we systematically moved a single AuNP along nanometer-size collagen fibers and actin filament inside chinese hamster ovary K1 living cells, mapping their 3D topography with high fidelity.

Gold nanoparticles-based protease assay

PubMed Central

Guarise, Cristian; Pasquato, Lucia; De Filippis, Vincenzo; Scrimin, Paolo

2006-01-01

We describe here a simple assay that allows the visual detection of a protease. The method takes advantage of the high molar absorptivity of the plasmon band of gold colloids and is based on the color change of their solution when treated with dithiols. We used C- and N-terminal cysteinyl derivatives of a peptide substrate exploiting its selective recognition and cleavage by a specific protease. Contrary to the native ones, cleaved peptides are unable to induce nanoparticles aggregation; hence, the color of the solution does not change. The detection of two proteases is reported: thrombin (involved in blood coagulation and thrombosis) and lethal factor (an enzyme component of the toxin produced by Bacillus anthracis). The sensitivity of this nanoparticle-based assay is in the low nanomolar range. PMID:16537471

Gold nanoparticles-based protease assay.

PubMed

Guarise, Cristian; Pasquato, Lucia; De Filippis, Vincenzo; Scrimin, Paolo

2006-03-14

We describe here a simple assay that allows the visual detection of a protease. The method takes advantage of the high molar absorptivity of the plasmon band of gold colloids and is based on the color change of their solution when treated with dithiols. We used C- and N-terminal cysteinyl derivatives of a peptide substrate exploiting its selective recognition and cleavage by a specific protease. Contrary to the native ones, cleaved peptides are unable to induce nanoparticles aggregation; hence, the color of the solution does not change. The detection of two proteases is reported: thrombin (involved in blood coagulation and thrombosis) and lethal factor (an enzyme component of the toxin produced by Bacillus anthracis). The sensitivity of this nanoparticle-based assay is in the low nanomolar range.

Magnetic nanoparticle-based drug delivery for cancer therapy.

PubMed

Tietze, Rainer; Zaloga, Jan; Unterweger, Harald; Lyer, Stefan; Friedrich, Ralf P; Janko, Christina; Pöttler, Marina; Dürr, Stephan; Alexiou, Christoph

2015-12-18

Nanoparticles have belonged to various fields of biomedical research for quite some time. A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles which are directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium [1]. In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so-called "magnetic drug targeting", MDT), has additionally emerged as a promising strategy of drug delivery. Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism-exploiting, tumor-specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. As it is nearly impossible to record every magnetic nanoparticle system developed so far, this review summarizes interesting approaches which have recently emerged in the field of targeted drug delivery for cancer therapy based on magnetic nanoparticles. Copyright © 2015 Elsevier Inc. All rights reserved.

A biosensor system using nickel ferrite nanoparticles

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

Singh, Prachi, E-mail: prachi.singh@st.niituniversity.in; Rathore, Deepshikha, E-mail: deep.nano@gmail.com

2016-05-06

NiFe{sub 2}O{sub 4} ferrite nanoparticles were synthesized by chemical co-precipitation method and the structural characteristics were investigated using X-ray diffraction technique, where single cubic phase formation of nanoparticles was confirmed. The average particle size of NiFe{sub 2}O{sub 4} was found to be 4.9 nm. Nanoscale magnetic materials are an important source of labels for biosensing due to their strong magnetic properties which are not found in biological systems. This property of the material was exploited and the fabrication of the NiFe{sub 2}O{sub 4} nanoparticle based biosensor was done in the form of a capacitor system, with NiFe{sub 2}O{sub 4} as themore » dielectric material. The biosensor system was tested towards different biological materials with the help of electrochemical workstation and the same was analysed through Cole-Cole plot of NiFe{sub 2}O{sub 4}. The performance of the sensor was determined based on its sensitivity, response time and recovery time.« less

Bio-mimetic mineralization potential of collagen hydrolysate obtained from chromium tanned leather waste.

PubMed

Banerjee, Pradipta; Madhu, S; Chandra Babu, N K; Shanthi, C

2015-04-01

Hydroxyapatite (HA) ceramics serve as an alternative to autogenous-free bone grafting by virtue of their excellent biocompatibility. However, chemically synthesized HA lacks the strong load-bearing capacity as required by bone. The bio-mimetic growth of HA crystals on collagen surface provides a feasible solution for synthesizing bone substitutes with the desired properties. This study deals with the utilization of the collagen hydrolysate recovered from leather waste as a substrate for promoting HA crystal growth. Bio-mimetic growth of HA was induced by subjecting the hydrolysate to various mineralization conditions. Parameters that would have a direct effect on crystal growth were varied to determine the optimal conditions necessary. Maximum mineralization was achieved with a combination of 10mM of CaCl2, 5mM of Na2HPO4, 100mM of NaCl and 0.575% glutaraldehyde at a pH of 7.4. The metal-protein interactions leading to formation of HA were identified through Fourier-transform infrared (FTIR) spectroscopy and x-ray diffraction (XRD) studies. The crystal dimensions were determined to be in the nanoscale range by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The size and crystallinity of bio-mimetically grown HA indicate that hydrolysate from leather waste can be used as an ideal alternative substrate for bone growth. Copyright © 2015 Elsevier B.V. All rights reserved.

Chitosan nanoparticle-based delivery of fused NKG2D–IL-21 gene suppresses colon cancer growth in mice

PubMed Central

Tan, Lunmei; Han, Sen; Ding, Shizhen; Xiao, Weiming; Ding, Yanbing; Qian, Li; Wang, Chenming; Gong, Weijuan

2017-01-01

Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21) have displayed antitumor activities through lymphocyte activation. The NKG2D–IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(−) plasmid. PcDNA3.1–dsNKG2D–IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D–IL-21 gene nanoparticles can activate natural killer (NK) and CD8+ T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D–IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for ~4–24 h. Treatment of dsNKG2D–IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D–IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy. PMID:28450784

Delivery of RNA interference therapeutics using polycation-based nanoparticles.

PubMed

Howard, Kenneth Alan

2009-07-25

RNAi-based therapies are dependent on extracellular and intracellular delivery of RNA molecules for enabling target interaction. Polycation-based nanoparticles (or polyplexes) formed by self-assembly with RNA can be used to modulate pharmacokinetics and intracellular trafficking to improve the therapeutic efficacy of RNAi-based therapeutics. This review describes the application of polyplexes for extracellular and intracellular delivery of synthetic RNA molecules. Focus is given to routes of administration and silencing effects in animal disease models. The inclusion of functional components into the nanoparticle for controlling cellular trafficking and RNA release is discussed. This work highlights the versatile nature of polycation-based nanoparticles to fulfil the delivery requirements for RNA molecules with flexibility in design to evolve alongside an expanding repertoire of RNAi-based drugs.

Compact solar autoclave based on steam generation using broadband light-harvesting nanoparticles.

PubMed

Neumann, Oara; Feronti, Curtis; Neumann, Albert D; Dong, Anjie; Schell, Kevin; Lu, Benjamin; Kim, Eric; Quinn, Mary; Thompson, Shea; Grady, Nathaniel; Nordlander, Peter; Oden, Maria; Halas, Naomi J

2013-07-16

The lack of readily available sterilization processes for medicine and dentistry practices in the developing world is a major risk factor for the propagation of disease. Modern medical facilities in the developed world often use autoclave systems to sterilize medical instruments and equipment and process waste that could contain harmful contagions. Here, we show the use of broadband light-absorbing nanoparticles as solar photothermal heaters, which generate high-temperature steam for a standalone, efficient solar autoclave useful for sanitation of instruments or materials in resource-limited, remote locations. Sterilization was verified using a standard Geobacillus stearothermophilus-based biological indicator.

Compact solar autoclave based on steam generation using broadband light-harvesting nanoparticles

PubMed Central

Neumann, Oara; Feronti, Curtis; Neumann, Albert D.; Dong, Anjie; Schell, Kevin; Lu, Benjamin; Kim, Eric; Quinn, Mary; Thompson, Shea; Grady, Nathaniel; Nordlander, Peter; Oden, Maria; Halas, Naomi J.

2013-01-01

The lack of readily available sterilization processes for medicine and dentistry practices in the developing world is a major risk factor for the propagation of disease. Modern medical facilities in the developed world often use autoclave systems to sterilize medical instruments and equipment and process waste that could contain harmful contagions. Here, we show the use of broadband light-absorbing nanoparticles as solar photothermal heaters, which generate high-temperature steam for a standalone, efficient solar autoclave useful for sanitation of instruments or materials in resource-limited, remote locations. Sterilization was verified using a standard Geobacillus stearothermophilus-based biological indicator. PMID:23836642

Adverse Biological Effect of TiO2 and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement

PubMed Central

Wang, Jiangxue; Wang, Liting; Fan, Yubo

2016-01-01

The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO2 nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris–mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants. PMID:27231896

Effect of natural extracts pH on morphological characteristics of hybrid materials based on gold nanoparticles

NASA Astrophysics Data System (ADS)

Olenic, L.; Vulcu, A.; Chiorean, I.; Crisan, M.; Berghian-Grosan, C.; Dreve, S.; David, L.; Tudoran, L. B.; Kacso, I.; Bratu, I.; Neamtu, C.; Voica, C.

2013-11-01

In the present paper we have investigated the pH influence on the morphology of some new hybrid materials based on gold nanoparticles and natural extracts from fruits of Romanian native plants of Adoxaceae family (Viburnum opulus L. and Sambucus nigra L.). It is well known that the natural plants extracts are beneficial for humans thanks to their antioxidant, anti-inflammatory and immunomodulatory effects. The biological activity of these berries is mainly due to their high content of anthocyanins and other polyphenols. The nanoparticles facilitate the penetration of substances in skin, enhancing their antimitotic, anti-inflammatory and antibiotic properties. We have chosen the optimal method to get these materials in which gold nanoparticles of 10-80 nm were obtained. We characterized them by UV-Vis and FT-IR spectroscopy, by TEM and DSC. Creams prepared with the hybrid materials have been tested on psoriatic lesions and the medical results emphasized a remarkable improvement in this diseases.

Arbitrary Order Mixed Mimetic Finite Differences Method with Nodal Degrees of Freedom

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

Iaroshenko, Oleksandr; Gyrya, Vitaliy; Manzini, Gianmarco

2016-09-01

In this work we consider a modification to an arbitrary order mixed mimetic finite difference method (MFD) for a diffusion equation on general polygonal meshes [1]. The modification is based on moving some degrees of freedom (DoF) for a flux variable from edges to vertices. We showed that for a non-degenerate element this transformation is locally equivalent, i.e. there is a one-to-one map between the new and the old DoF. Globally, on the other hand, this transformation leads to a reduction of the total number of degrees of freedom (by up to 40%) and additional continuity of the discrete flux.

A highly efficient colorimetric immunoassay using a nanocomposite entrapping magnetic and platinum nanoparticles in ordered mesoporous carbon.

PubMed

Kim, Moon Il; Ye, Youngjin; Woo, Min-Ah; Lee, Jinwoo; Park, Hyun Gyu

2014-01-01

Nanocomposite to achieve ultrafast immunoassay: a new synergistically integrated nanocomposite consisting of magnetic and platinum nanoparticles, simultaneously entrapped in mesoporous carbon, is developed as a promising enzyme mimetic candidate to achieve ultrafast colorimetric immunoassays. Using new assay system, clinically important target molecules, such as human epidermal growth factor receptor 2 (HER2) and diarrhea-causing rotavirus, can be detected in only 3 min at room temperature with high specificity and sensitivity. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of novel small-molecule Ulex europaeus I mimetics for targeted drug delivery.

PubMed

Hamashin, Christa; Spindler, Lisa; Russell, Shannon; Schink, Amy; Lambkin, Imelda; O'Mahony, Daniel; Houghten, Richard; Pinilla, Clemencia

2003-11-17

Lectin mimetics have been identified that may have potential application towards targeted drug delivery. Synthetic multivalent polygalloyl constructs effectively competed with Ulex europaeus agglutinin I (UEA1) for binding to intestinal Caco-2 cell membranes.

Nanoparticles for Imaging: Top or Flop?

PubMed Central

Mertens, Marianne E.; Grimm, Jan; Lammers, Twan

2014-01-01

Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential. PMID:25247562

Interactions of nanomaterials with biological systems: A study of bio-mineralized nanoparticles and nanoparticle antibiotics

NASA Astrophysics Data System (ADS)

Gifford, Jennifer Chappell

Nature is continually able to out-perform laboratory syntheses of nanomaterials with control of specific properties under ambient temperatures, pressures and pH. The investigation of existing biomolecule-mediated nanoparticle synthesis provides insight and knowledge necessary for duplicating these processes. In this way, peptides or proteins with nanomaterial mediation capabilities can be: 1) explored to further understand the ways in which biomolecules create specific nanoparticles then 2) used to create genetically encodable tags for use in electron tomography. The goal of designing such a tag was to assist in closing the resolution gap that exists in current imaging techniques between approximately 5 nm and 100 nm. Presented in this thesis are examples of peptides and proteins that form iron oxide, silver or gold nanoparticles under discrete circumstances. Three iron oxide-related bacterial proteins -- bacterioferritin, Dps and Mms6 -- were investigated for potential use. Similarly, a silver mineralizing peptide, Ge8, was studied upon attachment to the filamentous protein, FtsZ, and a gold mineralizing peptide, A3, was examined to characterize the way in which it mediates the formation of both Au0 nanoclusters and nanoparticles. Given the established interactions that occur between nanoparticles and biomolecules, it may not be surprising that gold nanoparticles displaying specific ratios of functional groups are able to interact with bacteria, in some cases inhibiting growth or causing cell death as antibiotics. A previously developed small molecule variable ligand display (SMVLD) method was expanded to identify a nanoparticle conjugate with a minimal inhibitory concentration (MIC99.9) of 6 muM for Mycobacterium smegmatis, a common laboratory model for M. tuberculosis and the first example of SMVLD applied to mycobacteria. Nanoparticle structure-activity relationships, modes of action and approximations of mammalian cell toxicities were also explored to expand

Development of peptoid-based ligands for the removal of cadmium from biological media

DOE PAGES

Knight, Abigail S.; Zhou, Effie Y.; Francis, Matthew B.

2015-05-14

Cadmium poisoning poses a serious health concern due to cadmium's increasing industrial use, yet there is currently no recommended treatment. The selective coordination of cadmium in a biological environment—i.e. in the presence of serum ions, small molecules, and proteins—is a difficult task. To address this challenge, a combinatorial library of peptoid-based ligands has been evaluated to identify structures that selectively bind to cadmium in human serum with minimal chelation of essential metal ions. Eighteen unique ligands were identified in this screening procedure, and the binding affinity of each was measured using metal titrations monitored by UV-vis spectroscopy. To evaluate themore » significance of each chelating moiety, sequence rearrangements and substitutions were examined. Analysis of a metal–ligand complex by NMR spectroscopy highlighted the importance of particular residues. Depletion experiments were performed in serum mimetics and human serum with exogenously added cadmium. These depletion experiments were used to compare and demonstrate the ability of these peptoids to remove cadmium from blood-like mixtures. In one of these depletion experiments, the peptoid sequence was able to deplete the cadmium to a level comparable to the reported acute toxicity limit. Evaluation of the metal selectivity in buffered solution and in human serum was performed to verify minimal off-target binding. These studies highlight a screening platform for the identification of metal–ligands that are capable of binding in a complex environment. They additionally demonstrate the potential utility of biologically-compatible ligands for the treatment of heavy metal poisoning.« less

Development of peptoid-based ligands for the removal of cadmium from biological media

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

Knight, Abigail S.; Zhou, Effie Y.; Francis, Matthew B.

Cadmium poisoning poses a serious health concern due to cadmium's increasing industrial use, yet there is currently no recommended treatment. The selective coordination of cadmium in a biological environment—i.e. in the presence of serum ions, small molecules, and proteins—is a difficult task. To address this challenge, a combinatorial library of peptoid-based ligands has been evaluated to identify structures that selectively bind to cadmium in human serum with minimal chelation of essential metal ions. Eighteen unique ligands were identified in this screening procedure, and the binding affinity of each was measured using metal titrations monitored by UV-vis spectroscopy. To evaluate themore » significance of each chelating moiety, sequence rearrangements and substitutions were examined. Analysis of a metal–ligand complex by NMR spectroscopy highlighted the importance of particular residues. Depletion experiments were performed in serum mimetics and human serum with exogenously added cadmium. These depletion experiments were used to compare and demonstrate the ability of these peptoids to remove cadmium from blood-like mixtures. In one of these depletion experiments, the peptoid sequence was able to deplete the cadmium to a level comparable to the reported acute toxicity limit. Evaluation of the metal selectivity in buffered solution and in human serum was performed to verify minimal off-target binding. These studies highlight a screening platform for the identification of metal–ligands that are capable of binding in a complex environment. They additionally demonstrate the potential utility of biologically-compatible ligands for the treatment of heavy metal poisoning.« less

Biologically synthesised silver nanoparticles from three diverse family of plant extracts and their anticancer activity against epidermoid A431 carcinoma.

PubMed

Nayak, Debasis; Pradhan, Sonali; Ashe, Sarbani; Rauta, Pradipta Ranjan; Nayak, Bismita

2015-11-01

Biological synthesis of silver nanoparticles is a cost effective natural process where the phytochemicals specifically phenols, flavonoids and terpenoids present in the plant extracts act as capping and reducing agent. Due to their nano size regime the silver nanoparticles may directly bind to the DNA of the pathogenic bacterial strains leading to higher antimicrobial activity. In the current study silver nanoparticles were synthesised using plant extracts from different origin Cucurbita maxima (petals), Moringa oleifera (leaves) and Acorus calamus (rhizome). The synthesised nanoparticles were characterized by UV-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), field emission scanning electron microscopy (Fe-SEM) and Fourier transform infrared spectroscopy (FTIR). Highly crystalline, roughly spherical and cuboidal silver nanoparticles of 30-70 nm in size were synthesised. The nanoparticles provided strong antimicrobial activity against pathogenic strains. The effect of the synthesised nanoparticles against A431 skin cancer cell line was tested for their toxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. The IC50 values of 82.39±3.1, 83.57±3.9 and 78.58±2.7 μg/ml were calculated for silver nanoparticles synthesised by C. maxima, M. oleifera and A. calamus respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

Do physico-chemical properties of silver nanoparticles decide their interaction with biological media and bactericidal action? A review.

PubMed

Pareek, Vikram; Gupta, Rinki; Panwar, Jitendra

2018-09-01

The unprecedented increase in antibiotic resistance in this era has resuscitated the attention of scientific community to exploit silver and its various species as antimicrobial agents. Plenty of studies have been done to measure the antimicrobial potential of silver species (cationic silver, metallic Ag 0 or silver nanoparticles, silver oxide particulates etc.) and indicated that membrane damage, oxidative stress, protein dysfunction and DNA damage to be the possible cause of injury to the microbial cell. However, the precise molecular mechanism of their mode of action has remained unclear, which makes an obstacle towards the generation of potential antibacterial agent against various pathogenic and multidrug resistant (MDR) bacteria. In order to endeavor this issue, one should first have the complete understanding about the resistance mechanisms present in bacteria that can be a therapeutic target for the silver-based drug formulations. Apart from this, in-depth understanding of the interactions of various silver species (with the biological media) is a probable deciding factor for the synthesis of silver-based drug formulations because the particular form and physico-chemical properties of silver can ultimately decide their antimicrobial action. In context to above mentioned serious concerns, the present article aims to discuss the mechanisms behind the confrontation of bacteria against various drugs and the effect of physico-chemical properties of silver species on their bactericidal action as well as critically evaluates the available reports on bacterial transcriptomic and proteomic profiles upon the exposure of various silver species. Further, this review state the mechanism of action that needs to be followed for the complete understanding of toxic potential of silver nanoparticles, which will open a possibility to synthesize new silver nanoparticle based antimicrobial systems with desired properties to ensure their safe use, exposure over extended period

Nanoparticle-based drug delivery to the vagina: a review

PubMed Central

Ensign, Laura M.; Cone, Richard; Hanes, Justin

2014-01-01

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

Nanoparticles as biochemical sensors

PubMed Central

El-Ansary, Afaf; Faddah, Layla M

2010-01-01

There is little doubt that nanoparticles offer real and new opportunities in many fields, such as biomedicine and materials science. Such particles are small enough to enter almost all areas of the body, including cells and organelles, potentially leading to new approaches in nanomedicine. Sensors for small molecules of biochemical interest are of critical importance. This review is an attempt to trace the use of nanomaterials in biochemical sensor design. The possibility of using nanoparticles functionalized with antibodies as markers for proteins will be elucidated. Moreover, capabilities and applications for nanoparticles based on gold, silver, magnetic, and semiconductor materials (quantum dots), used in optical (absorbance, luminescence, surface enhanced Raman spectroscopy, surface plasmon resonance), electrochemical, and mass-sensitive sensors will be highlighted. The unique ability of nanosensors to improve the analysis of biochemical fluids is discussed either through considering the use of nanoparticles for in vitro molecular diagnosis, or in the biological/biochemical analysis for in vivo interaction with the human body. PMID:24198472

Nanoparticle-based photodynamic therapy on non-melanoma skin cancer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Arce-Diego, J. L.

2018-02-01

There are several advantages of Photodynamic Therapy (PDT) for nonmelanoma skin cancer treatment compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages its noninvasive nature, the use of non ionizing radiation and its high selectivity can be mentioned. Despite all these advantages, the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. An adequate dosimetry is needed in order to personalize the protocol. There are strategies that try to overcome the current PDT shortcomings, such as the improvement of the photosensitizer accumulation in the target tissue, optical radiation distribution optimization or photochemical reactions maximization. These strategies can be further complemented by the use of nanostructures with conventional PDT. Customized dosimetry for nanoparticle-based PDT requires models in order to adjust parameters of different nature to get an optimal tumor removal. In this work, a predictive model of nanoparticle-based PDT is proposed and analyzed. Dosimetry in nanoparticle-based PDT is going to be influenced by photosensitizer-nanoparticle distribution in the malignant tissue, its influence in the optical radiation distribution and the subsequent photochemical reactions. Nanoparticles are considered as photosensitizer carriers on several types of non-melanoma skin cancer. Shielding effects are taken into account. The results allow to compare the estimated treatment outcome with and without nanoparticles.

Nanoparticle-based Therapies for Wound Biofilm Infection: Opportunities and Challenges

PubMed Central

Kim, Min-Ho

2016-01-01

Clinical data from human chronic wounds implicates biofilm formation with the onset of wound chronicity. Despite the development of novel antimicrobial agents, the cost and complexity of treating chronic wound infections associated with biofilms remain a serious challenge, which necessitates the development of new and alternative approaches for effective anti-biofilm treatment. Recent advancement in nanotechnology for developing a new class of nanoparticles that exhibit unique chemical and physical properties holds promise for the treatment of biofilm infections. Over the last decade, nanoparticle-based approaches against wound biofilm infection have been directed toward developing nanoparticles with intrinsic antimicrobial properties, utilizing nanoparticles for controlled antimicrobials delivery, and applying nanoparticles for antibacterial hyperthermia therapy. In addition, a strategy to functionalize nanoparticles towards enhanced penetration through the biofilm matrix has been receiving considerable interest recently by means of achieving an efficient targeting to the bacterial cells within biofilm matrix. This review summarizes and highlights the recent development of these nanoparticle-based approaches as potential therapeutics for controlling wound biofilm infection, along with current challenges that need to be overcome for their successful clinical translation. PMID:26955044

Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

EPA Science Inventory

ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles.

PubMed

Seynhaeve, Ann L B; Ten Hagen, Timo L M

2017-11-01

Conventional imaging techniques can provide detailed information about cellular processes. However, this information is based on static images in an otherwise dynamic system, and successive phases are easily overlooked or misinterpreted. Live-cell imaging and time-lapse microscopy, in which living cells can be followed for hours or even days in a more or less continuous fashion, are therefore very informative. The protocol described here allows for the investigation of the fate of chemotherapeutic nanoparticles after the delivery of doxorubicin (dox) in living cells. Dox is an intercalating agent that must be released from its nanocarrier to become biologically active. In spite of its clinical registration for more than two decades, its uptake, breakdown, and drug release are still not fully understood. This article explores the hypothesis that lipid-based nanoparticles are taken up by the tumor cells and are slowly degraded. Released dox is then translocated to the nucleus. To prevent fixation artifacts, live-cell imaging and time-lapse microscopy, described in this experimental procedure, can be applied.

A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide.

PubMed

Roh, Changhyun

2012-01-01

Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS), and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (-)-catechin gallate and (-)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (-)-catechin gallate and (-)-gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 μg mL(-1), (-)-catechin gallate and (-)-gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system.

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems

DOE PAGES

Phan, Manh-Huong; Alonso, Javier; Khurshid, Hafsa; ...

2016-11-23

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and relatedmore » phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.« less

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems

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

Phan, Manh-Huong; Alonso, Javier; Khurshid, Hafsa

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and relatedmore » phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.« less

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems

PubMed Central

Phan, Manh-Huong; Alonso, Javier; Khurshid, Hafsa; Lampen-Kelley, Paula; Chandra, Sayan; Stojak Repa, Kristen; Nemati, Zohreh; Das, Raja; Iglesias, Óscar; Srikanth, Hariharan

2016-01-01

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and related phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications. PMID:28335349

Scope and limitations of carbohydrate hydrolysis for de novo glycan sequencing using a hydrogen peroxide/metallopeptide-based glycosidase mimetic.

PubMed

Peng, Tianyuan; Wooke, Zachary; Pohl, Nicola L B

2018-03-22

Acidic hydrolysis is commonly used as a first step to break down oligo- and polysaccharides into monosaccharide units for structural analysis. While easy to set up and amenable to mass spectrometry detection, acid hydrolysis is not without its drawbacks. For example, ring-destruction side reactions and degradation products, along with difficulties in optimizing conditions from analyte to analyte, greatly limits its broad utility. Herein we report studies on a hydrogen peroxide/CuGGH metallopeptide-based glycosidase mimetic design for a more efficient and controllable carbohydrate hydrolysis. A library of methyl glycosides consisting of ten common monosaccharide substrates, along with oligosaccharide substrates, was screened with the artificial glycosidase for hydrolytic activity in a high-throughput format with a robotic liquid handling system. The artificial glycosidase was found to be active towards most screened linkages, including alpha- and beta-anomers, thus serving as a potential alternative method for traditional acidic hydrolysis approaches of oligosaccharides. Copyright © 2018 Elsevier Ltd. All rights reserved.

Harnessing Functionalized Polysaccharides for Medical and Dental Applications

NASA Astrophysics Data System (ADS)

Jones, Nathan A.

Polysaccharides are an important class of biomolecules with many different biological functions and unique properties, thus it is unsurprising that polysaccharides are heavily researched as materials solutions in medicine and dentistry. This dissertation explores the potential of harnessing inherent and well-understood biological properties of polysaccharides, using chemical and materials modification techniques to create clinically useful systems for medical and dental challenges. Engineered polysaccharides systems were prepared and characterized, including starch nanoparticles with control of particle size, charge, loading, and attachment of functional molecules, and glycocalyx-mimetic polymer brushes. These systems were applied as a diagnostic aid for dental caries, as an anti-bacterial treatment, and in targeting tumor-associated macrophages. In the first application, fluorescent cationic (+5.8+/-1.2 mV) starch nanoparticles (size 101+/-56 nm) were prepared to target and adhere to early caries lesions to facilitate optical detection, test lesion activity, and monitor the impact of remineralization treatments in vitro. In the second application, similarly designed starch nanoparticles (size 440+/-58 nm) were loaded with antibacterial copper nanoparticles (6-7nm size, ˜0.35% loading) to create a system which targets bacteria electrostatically and by their enzymatic metabolic processes. This system showed high antibacterial efficacy (3-log and 7-log bacterial reductions for S. aureus and B. subtilis, respectively, for copper nanoparticle dose of 17 mug/ml). The final application demonstrated high positive predictive value (>0.8 for M2 over M1) for cellular binding of glycocalyx-mimetic mannose-coatings with M2-polarized tumor-associated macrophages, with potential applications in cancer diagnostics and therapeutics. These examples highlight the utility of modified polysaccharides in the design of clinically useful systems in medicine and dentistry.

Smac mimetic enables the anticancer action of BCG-stimulated neutrophils through TNF-α but not through TRAIL and FasL.

PubMed

Jinesh G, Goodwin; Chunduru, Srinivas; Kamat, Ashish M

2012-07-01

BCG, the current gold standard immunotherapy for bladder cancer, exerts its activity via recruitment of neutrophils to the tumor microenvironment. Many patients do not respond to BCG therapy, indicating the need to understand the mechanism of action of BCG-stimulated neutrophils and to identify ways to overcome resistance to BCG therapy. Using isolated human neutrophils stimulated with BCG, we found that TNF-α is the key mediator secreted by BCG-stimulated neutrophils. RT4v6 human bladder cancer cells, which express TNFR1, CD95/Fas, CD95 ligand/FasL, DR4, and DR5, were resistant to BCG-stimulated neutrophil conditioned medium but effectively killed by the combination of conditioned medium and Smac mimetic. rhTNF-α and rhFasL, but not rhTRAIL, in combination with Smac mimetic, generated signature molecular events similar to those produced by BCG-stimulated neutrophils in combination with Smac mimetic. However, experiments using neutralizing antibodies to these death ligands showed that TNF-α secreted from BCG-stimulated neutrophils was the key mediator of anticancer action. These findings explain the mechanism of action of BCG and identified Smac mimetics as potential combination therapeutic agents for bladder cancer.

Directed-assembly of ordered nanoparticle arrays exploiting multiple adsorption mechanisms on a self-assembling biological template

NASA Astrophysics Data System (ADS)

Shindel, Matthew M.

Developing processes to fabricate inorganic architectures with designer functionalities at increasingly minute length-scales is of chief concern in the fields of nanotechnology and nanoscience. This enterprise requires assembly mechanisms with the capacity to tailor both the spatial arrangement and material composition of a system's constituent building blocks. To this end, significant advances can be made by turning to biology, as the natural world has evolved the ability to generate intricate nanostructures, which can potentially be employed as templates for inorganic nanosystems. We explore this biotemplating methodology using two-dimensional streptavidin crystals, investigating the ability of the protein lattice to direct the assembly of ordered metallic nanoparticle arrays. We demonstrate that the adsorption of nanoparticles on the protein monolayer can be induced through both electrostatic and molecular recognition (ligand-receptor) interactions. Furthermore, the dynamics of adsorption can be modulated through both environmental factors (e.g. pH), and by tailoring particle surface chemistry. When the characteristic nanoparticle size is on the order of the biotemplate's unit-cell dimension, electrostatically-mediated adsorption occurs in a site-specific manner. The nanoparticles exhibit a pronounced preference for adhering to the areas between protein molecules. The two-dimensional structure of the resultant nanoparticle ensemble consequently conforms to that of the underlying protein crystal. Through theoretical calculations, simulation and experiment, we show that interparticle spacing in the templated array is influenced by the screened-coulombic repulsion between particles, and can thus be tuned by controlling ionic strength during deposition. Templating ordered nanoparticle arrays via ligand-receptor mediated adsorption, and the constrained growth of metallic nanoparticles directly on the protein lattice from ionic precursors are also examined. Overall

The green synthesis, characterization, and evaluation of the biological activities of silver nanoparticles synthesized from Leptadenia reticulata leaf extract

NASA Astrophysics Data System (ADS)

Kumara Swamy, M.; Sudipta, K. M.; Jayanta, K.; Balasubramanya, S.

2015-01-01

Biosynthesis of silver nanoparticles (Ag Nps) was carried out using methanol leaves extract of L. reticulata. Ag Nps were characterized based on the observations of UV-visible spectroscopy, transmission electron microscopy, and X-ray diffraction (XRD) analysis. These Ag Nps were tested for antimicrobial activity by agar well diffusion method against different pathogenic microorganisms and antioxidant activity was performed using DPPH assay. Further, the in vitro cytotoxic effects of Ag Nps were screened against HCT15 cancer cell line and viability of tumor cells was confirmed using MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole)) assay. The nuclear condensation was studied using the propidium iodide-staining method. The color change from green to dark brown and the absorbance peak at about 420 nm indicated the formation of nanoparticles. XRD pattern showed characteristic peaks indexed to the crystalline planes (111), (200) and (220) of face-centered cubic silver. The nanoparticles were of spherical shape with varying sizes ranging from 50 to 70 nm. Biosynthesized Ag Nps showed potent antibacterial activity and effective radical scavenging activity. MTT assay revealed a dose-dependent decrease in cell viability. Microscopic observations showed distinct cellular morphological changes indicating unhealthy cells, whereas the control appeared normal. Increase in the number of propidium iodide positive cells were observed in maximum concentration. Methanolic leaf extract of L. reticulata acts as an excellent capping agent for the formation of silver nanoparticles and demonstrates immense biological activities. Hence, these Ag NPs can be used as antibacterial, antioxidant as well as cytotoxic agent in treating many medical complications.

Self-organization, interfacial interaction and photophysical properties of gold nanoparticle complexes derived from resilin-mimetic fluorescent protein rec1-resilin.

PubMed

Mayavan, Sundar; Dutta, Naba K; Choudhury, Namita R; Kim, Misook; Elvin, Christopher M; Hill, Anita J

2011-04-01

In this investigation we report the synthesis of optically coupled hybrid architectures based on a new biomimetic fluorescent protein rec1-resilin and nanometer-scale gold nanoparticles (AuNPs) in a one-step method using a non-covalent mode of binding protocol. The presence of uniformly distributed fluorophore sequences, -Ser(Thr)-Tyr-Gly- along the molecular structure of rec1-resilin provides significant opportunity to synthesize fluorophore-modified AuNPs bioconjugates with unique photophysical properties. The detailed analyses of the AuNP-bioconjugates, synthesized under different experimental conditions using spectroscopic, microscopic and scattering techniques demonstrate the organizational pathways and the electronic and photophysical properties of the developed AuNP-rec1-resilin bioconjugates. The calculation of the bimolecular quenching constant using the Stern-Volmer equation confirms that the dominant mechanism involved in quenching of fluorescence of rec1-resilin in the presence of AuNP is static. Photoacoustic infrared spectroscopy was employed to understand the nature of the interfacial interaction between the AuNP and rec1-resilin and its evolution with pH. In such bioconjugates the quenched emission of fluorescence by AuNP on the fluorophore moiety of rec1-resilin in the immediate vicinity of the AuNP has significant potential for fluorescence-based detection schemes, sensors and also can be incorporated into nanoparticle-based devices. Copyright © 2011 Elsevier Ltd. All rights reserved.

Size-separation of silver nanoparticles using sucrose gradient centrifugation

DOE PAGES

Suresh, Anil K.; Pelletier, Dale A.; Moon, Ji Won; ...

2015-08-28

Size and shape distributions of nanoparticles can drastically contribute to the overall properties of nanoparticles, thereby influencing their interaction with different chemotherapeutic molecules, biological organisms and or materials and cell types. Therefore, to exploit the proper use of nanoparticles for various biomedical and biosensor applications, it is important to obtain well-separated monodispersed nanoparticles. However, gaining precise control over the morphological characteristics of nanoparticles during their synthesis is often a challenging task. Consequently, post-synthesis separation of nanoparticles is necessary. In the present study, we demonstrate the successful one-pot post-synthesis separation of anisotropic silver nanoparticles to near modispersities using sucrose density gradientmore » sedimentation. The separation of the nanoparticles was evidenced based on optical confirmation, and spectrophotometric and transmission electron microscopy measurements. Our results clearly demonstrate the facile separation of anisotropic silver nanoparticles using sucrose density gradient sedimentation and can enable the use of nanoparticles for various biomedical applications.« less

Size-separation of silver nanoparticles using sucrose gradient centrifugation

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

Suresh, Anil K.; Pelletier, Dale A.; Moon, Ji Won

Size and shape distributions of nanoparticles can drastically contribute to the overall properties of nanoparticles, thereby influencing their interaction with different chemotherapeutic molecules, biological organisms and or materials and cell types. Therefore, to exploit the proper use of nanoparticles for various biomedical and biosensor applications, it is important to obtain well-separated monodispersed nanoparticles. However, gaining precise control over the morphological characteristics of nanoparticles during their synthesis is often a challenging task. Consequently, post-synthesis separation of nanoparticles is necessary. In the present study, we demonstrate the successful one-pot post-synthesis separation of anisotropic silver nanoparticles to near modispersities using sucrose density gradientmore » sedimentation. The separation of the nanoparticles was evidenced based on optical confirmation, and spectrophotometric and transmission electron microscopy measurements. Our results clearly demonstrate the facile separation of anisotropic silver nanoparticles using sucrose density gradient sedimentation and can enable the use of nanoparticles for various biomedical applications.« less

Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle.

PubMed

Saptarshi, Shruti R; Duschl, Albert; Lopata, Andreas L

2013-07-19

Interaction of nanoparticles with proteins is the basis of nanoparticle bio-reactivity. This interaction gives rise to the formation of a dynamic nanoparticle-protein corona. The protein corona may influence cellular uptake, inflammation, accumulation, degradation and clearance of the nanoparticles. Furthermore, the nanoparticle surface can induce conformational changes in adsorbed protein molecules which may affect the overall bio-reactivity of the nanoparticle. In depth understanding of such interactions can be directed towards generating bio-compatible nanomaterials with controlled surface characteristics in a biological environment. The main aim of this review is to summarise current knowledge on factors that influence nanoparticle-protein interactions and their implications on cellular uptake.

Phenotypic and Genetic Divergence among Poison Frog Populations in a Mimetic Radiation

PubMed Central

Twomey, Evan; Yeager, Justin; Brown, Jason Lee; Morales, Victor; Cummings, Molly; Summers, Kyle

2013-01-01

The evolution of Müllerian mimicry is, paradoxically, associated with high levels of diversity in color and pattern. In a mimetic radiation, different populations of a species evolve to resemble different models, which can lead to speciation. Yet there are circumstances under which initial selection for divergence under mimicry may be reversed. Here we provide evidence for the evolution of extensive phenotypic divergence in a mimetic radiation in Ranitomeya imitator, the mimic poison frog, in Peru. Analyses of color hue (spectral reflectance) and pattern reveal substantial divergence between morphs. However, we also report that there is a “transition-zone” with mixed phenotypes. Analyses of genetic structure using microsatellite variation reveals some differentiation between populations, but this does not strictly correspond to color pattern divergence. Analyses of gene flow between populations suggest that, while historical levels of gene flow were low, recent levels are high in some cases, including substantial gene flow between some color pattern morphs. We discuss possible explanations for these observations. PMID:23405150

Compensatory and mimetic conditioned responses to effects of heroin in addicted persons.

PubMed

Trujillo, Humberto M; Oviedo-Joekes, Eugenia; Vargas, Cristina

2006-02-01

Study 1: The aim of this study was to analyze in persons detoxified of heroin, compensatory conditioned responses (CCRs) that are opposite to the unconditioned physiological, and subjective effects that are induced by this substance. The procedure consisted in presenting slides with images of neutral stimuli (NSs) and conditioned stimuli (CSs) of heroin to both non-addicted and detoxified addicted persons. The evaluated responses were heart rate (HR) and desire for heroin (DH). Study 2: The aim was to facilitate the emission of mimetic conditioned responses (MCRs) to the unconditioned physiological, and subjective effects of heroin in detoxified heroin addicts. Three different stimulus series were manipulated: SA, during which the participant remained alone; SB, administration of a needle prick given by the researcher; SC, performance of the "pump" ritual without drug by the participants. The responses measured were HR and DH. The results of both studies are considered, respectively, to be indicators of compensatory and mimetic conditioned responses.

Advances in silica based nanoparticles for targeted cancer therapy.

PubMed

Yang, Yannan; Yu, Chengzhong

2016-02-01

Targeted delivery of anticancer drug specifically to tumor site without damaging normal tissues has been the dream of all scientists fighting against cancer for decades. Recent breakthrough on nanotechnology based medicines has provided a possible tool to solve this puzzle. Among diverse nanomaterials that are under development and extensive study, silica based nanoparticles with vast advantages have attracted great attention. In this review, we concentrate on the recent progress using silica based nanoparticles, particularly mesoporous silica nanoparticles (MSNs), for targeted drug delivery applications. First, we discuss the passive targeting capability of silica based nanoparticles in relation to their physiochemical properties. Then, we focus on the recent advances of active targeting strategies involving tumor cell targeting, vascular targeting, nuclear targeting and multistage targeting, followed by an introduction to magnetic field directed targeting approach. We conclude with our personal perspectives on the remaining challenges and the possible future directions. Chemotherapy has been one of the mainstays of cancer treatment. The advances in nanotechnology has allowed the development of novel carrier systems for the delivery of anticancer drugs. Mesoporous silica has shown great promise in this respect. In this review article, the authors provided a comprehensive overview of the use of this nanoparticle in both passive, as well as active targeting in the field of oncology. The advantages of this particle were further discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

The reconstruction of f(ϕ)R and mimetic gravity from viable slow-roll inflation

NASA Astrophysics Data System (ADS)

Odintsov, S. D.; Oikonomou, V. K.

2018-04-01

In this work, we extend the bottom-up reconstruction framework of F (R) gravity to other modified gravities, and in particular for f (ϕ) R and mimetic F (R) gravities. We investigate which are the important conditions in order for the method to work, and we study several viable cosmological evolutions, focusing on the inflationary era. Particularly, for the f (ϕ) R theory case, we specify the functional form of the Hubble rate and of the scalar-to-tensor ratio as a function of the e-foldings number and accordingly, the rest of the physical quantities and also the slow-roll and the corresponding observational indices can be calculated. The same method is applied in the mimetic F (R) gravity case, and in both cases we thoroughly analyze the resulting free parameter space, in order to show that the viability of the models presented is guaranteed and secondly that there is a wide range of values of the free parameters for which the viability of the models occurs. In addition, the reconstruction method is also studied in the context of mimetic F (R) = R gravity. As we demonstrate, the resulting theory is viable, and also in this case, only the scalar-to-tensor ratio needs to be specified, since the rest follow from this condition. Finally, we discuss in brief how the reconstruction method could function for other modified gravities.

Promising iron oxide-based magnetic nanoparticles in biomedical engineering.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Vo, Toi Van; Lee, Beom-Jin

2012-12-01

For the past few decades biomedical engineering has imprinted its significant impact on the map of science through its wide applications on many other fields. An important example obviously proving this fact is the versatile application of magnetic nanoparticles in theranostics. Due to preferable properties such as biocompatibility, non-toxicity compared to other metal derivations, iron oxide-based magnetic nanoparticles was chosen to be addressed in this review. Aim of this review is to give the readers a whole working window of these magnetic nanoparticles in the current context of science. Thus, preparation of magnetic iron oxide nanoparticles with the so-far techniques, methods of characterizing the nanoparticles as well as their most recent biomedical applications will be stated.

Strategies for interfacing inorganic nanocrystals with biological systems based on polymer-coating.

PubMed

Palui, Goutam; Aldeek, Fadi; Wang, Wentao; Mattoussi, Hedi

2015-01-07

Interfacing inorganic nanoparticles and biological systems with the aim of developing novel imaging and sensing platforms has generated great interest and much activity. However, the effectiveness of this approach hinges on the ability of the surface ligands to promote water-dispersion of the nanoparticles with long term colloidal stability in buffer media. These surface ligands protect the nanostructures from the harsh biological environment, while allowing coupling to target molecules, which can be biological in nature (e.g., proteins and peptides) or exhibit specific photo-physical characteristics (e.g., a dye or a redox-active molecule). Amphiphilic block polymers have provided researchers with versatile molecular platforms with tunable size, composition and chemical properties. Hence, several groups have developed a wide range of polymers as ligands or micelle capsules to promote the transfer of a variety of inorganic nanomaterials to buffer media (including magnetic nanoparticles and semiconductor nanocrystals) and render them biocompatible. In this review, we first summarize the established synthetic routes to grow high quality nanocrystals of semiconductors, metals and metal oxides. We then provide a critical evaluation of the recent developments in the design, optimization and use of various amphiphilic copolymers to surface functionalize the above nanocrystals, along with the strategies used to conjugate them to target biomolecules. We finally conclude by providing a summary of the most promising applications of these polymer-coated inorganic platforms in sensor design, and imaging of cells and tissues.

Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis

PubMed Central

Ryan, Lisa K.; Freeman, Katie B.; Masso-Silva, Jorge A.; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G.; Fatahzadeh, Mahnaz; Scott, Richard W.

2014-01-01

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis. PMID:24752272

Student-Driven Design of Peptide Mimetics: Microwave-Assisted Synthesis of Peptoid Oligomers

ERIC Educational Resources Information Center

Pohl, Nicola L. B.; Kirshenbaum, Kent; Yoo, Barney; Schulz, Nathan; Zea, Corbin J.; Streff, Jennifer M.; Schwarz, Kimberly L.

2011-01-01

An experiment for the undergraduate organic laboratory is described in which peptide mimetic oligomers called "peptoids" are built stepwise on a solid-phase resin. Students employ two modern strategies to facilitate rapid multistep syntheses: solid-phase techniques to obviate the need for intermediate purifications and microwave irradiation to…

Polyketide mimetics yield structural and mechanistic insights into product template domain function in nonreducing polyketide synthases

PubMed Central

Barajas, Jesus F.; Shakya, Gaurav; Moreno, Gabriel; Rivera, Heriberto; Jackson, David R.; Topper, Caitlyn L.; Vagstad, Anna L.; La Clair, James J.; Townsend, Craig A.; Burkart, Michael D.; Tsai, Shiou-Chuan

2017-01-01

Product template (PT) domains from fungal nonreducing polyketide synthases (NR-PKSs) are responsible for controlling the aldol cyclizations of poly-β-ketone intermediates assembled during the catalytic cycle. Our ability to understand the high regioselective control that PT domains exert is hindered by the inaccessibility of intrinsically unstable poly-β-ketones for in vitro studies. We describe here the crystallographic application of “atom replacement” mimetics in which isoxazole rings linked by thioethers mimic the alternating sites of carbonyls in the poly-β-ketone intermediates. We report the 1.8-Å cocrystal structure of the PksA PT domain from aflatoxin biosynthesis with a heptaketide mimetic tethered to a stably modified 4′-phosphopantetheine, which provides important empirical evidence for a previously proposed mechanism of PT-catalyzed cyclization. Key observations support the proposed deprotonation at C4 of the nascent polyketide by the catalytic His1345 and the role of a protein-coordinated water network to selectively activate the C9 carbonyl for nucleophilic addition. The importance of the 4′-phosphate at the distal end of the pantetheine arm is demonstrated to both facilitate delivery of the heptaketide mimetic deep into the PT active site and anchor one end of this linear array to precisely meter C4 into close proximity to the catalytic His1345. Additional structural features, docking simulations, and mutational experiments characterize protein–substrate mimic interactions, which likely play roles in orienting and stabilizing interactions during the native multistep catalytic cycle. These findings afford a view of a polyketide “atom-replaced” mimetic in a NR-PKS active site that could prove general for other PKS domains. PMID:28484029

"Chemical transformers" from nanoparticle ensembles operated with logic.

PubMed

Motornov, Mikhail; Zhou, Jian; Pita, Marcos; Gopishetty, Venkateshwarlu; Tokarev, Ihor; Katz, Evgeny; Minko, Sergiy

2008-09-01

The pH-responsive nanoparticles were coupled with information-processing enzyme-based systems to yield "smart" signal-responsive hybrid systems with built-in Boolean logic. The enzyme systems performed AND/OR logic operations, transducing biochemical input signals into reversible structural changes (signal-directed self-assembly) of the nanoparticle assemblies, thus resulting in the processing and amplification of the biochemical signals. The hybrid system mimics biological systems in effective processing of complex biochemical information, resulting in reversible changes of the self-assembled structures of the nanoparticles. The bioinspired approach to the nanostructured morphing materials could be used in future self-assembled molecular robotic systems.

Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria.

PubMed

Naqvi, Syed Zeeshan Haider; Kiran, Urooj; Ali, Muhammad Ishtiaq; Jamal, Asif; Hameed, Abdul; Ahmed, Safia; Ali, Naeem

2013-01-01

Biological synthesis of nanoparticles is a growing innovative approach that is relatively cheaper and more environmentally friendly than current physicochemical processes. Among various microorganisms, fungi have been found to be comparatively more efficient in the synthesis of nanomaterials. In this research work, extracellular mycosynthesis of silver nanoparticles (AgNPs) was probed by reacting the precursor salt of silver nitrate (AgNO3) with culture filtrate of Aspergillus flavus. Initially, the mycosynthesis was regularly monitored by ultraviolet-visible spectroscopy, which showed AgNP peaks of around 400-470 nm. X-ray diffraction spectra revealed peaks of different intensities with respect to angle of diffractions (2θ) corresponding to varying configurations of AgNPs. Transmission electron micrographs further confirmed the formation of AgNPs in size ranging from 5-30 nm. Combined and individual antibacterial activities of the five conventional antibiotics and AgNPs were investigated against eight different multidrug-resistant bacterial species using the Kirby-Bauer disk-diffusion method. The decreasing order of antibacterial activity (zone of inhibition in mm) of antibiotics, AgNPs, and their conjugates against bacterial group (average) was; ciprofloxacin + AgNPs (23) . imipenem + AgNPs (21) > gentamycin + AgNPs (19) > vancomycin + AgNPs (16) > AgNPs (15) . imipenem (14) > trimethoprim + AgNPs (14) > ciprofloxacin (13) > gentamycin (11) > vancomycin (4) > trimethoprim (0). Overall, the synergistic effect of antibiotics and nanoparticles resulted in a 0.2-7.0 (average, 2.8) fold-area increase in antibacterial activity, which clearly revealed that nanoparticles can be effectively used in combination with antibiotics in order to improve their efficacy against various pathogenic microbes.

Mechanical characteristics of mesenchymal stem cells under impact of silica-based nanoparticles

NASA Astrophysics Data System (ADS)

Ogneva, Irina V.; Buravkov, Sergey V.; Shubenkov, Alexander N.; Buravkova, Ludmila B.

2014-06-01

Silica-based nanoparticles (NPs) pose great potential for medical and biological applications; however, their interactions with living cells have not been investigated in full. The objective of this study was to analyze the mechanical characteristics of mesenchymal stem cells when cultured in the presence of silica (Si) and silica-boron (SiB) nanoparticles. Cell stiffness was measured using atomic force microscopy; F-actin structure was evaluated using TRITC-phalloidin by confocal microscopy. The obtained data suggested that the cell stiffness increased within the following line: `Control' - `Si' - `SiB' (either after 1-h cultivation or 24-h incubation). Moreover, the cell stiffness was found to be higher after 1-h cultivation as compared to 24-h cultivation. This result shows that there is a two-phase process of particle diffusion into cells and that the particles interact directly with the membrane and, further, with the submembranous cytoskeleton. Conversely, the intensity of phalloidin fluorescence dropped within the same line: Control - Si - SiB. It could be suggested that the effects of silica-based particles may result in structural reorganization of cortical cytoskeleton with subsequent stiffness increase and concomitant F-actin content decrease (for example, in recruitment of additional actin-binding proteins within membrane and regrouping of actin filaments).

Mechanical characteristics of mesenchymal stem cells under impact of silica-based nanoparticles.

PubMed

Ogneva, Irina V; Buravkov, Sergey V; Shubenkov, Alexander N; Buravkova, Ludmila B

2014-01-01

Silica-based nanoparticles (NPs) pose great potential for medical and biological applications; however, their interactions with living cells have not been investigated in full. The objective of this study was to analyze the mechanical characteristics of mesenchymal stem cells when cultured in the presence of silica (Si) and silica-boron (SiB) nanoparticles. Cell stiffness was measured using atomic force microscopy; F-actin structure was evaluated using TRITC-phalloidin by confocal microscopy. The obtained data suggested that the cell stiffness increased within the following line: 'Control' - 'Si' - 'SiB' (either after 1-h cultivation or 24-h incubation). Moreover, the cell stiffness was found to be higher after 1-h cultivation as compared to 24-h cultivation. This result shows that there is a two-phase process of particle diffusion into cells and that the particles interact directly with the membrane and, further, with the submembranous cytoskeleton. Conversely, the intensity of phalloidin fluorescence dropped within the same line: Control - Si - SiB. It could be suggested that the effects of silica-based particles may result in structural reorganization of cortical cytoskeleton with subsequent stiffness increase and concomitant F-actin content decrease (for example, in recruitment of additional actin-binding proteins within membrane and regrouping of actin filaments).

Biologically Derived Nanoparticle Arrays via a Site-Specific Reconstitution of Ferritin and their Electrochemistry

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; King, Glen C.; Elliott, James R.; Chu, Sang-Hyon; Park, Yeonjoon; Watt, Gerald D.

2004-01-01

Nanoparticle arrays biologically derived from an electrochemically-controlled site-specific biomineralization were fabricated on a gold substrate through the immobilization process of biomolecules. The work reported herein includes the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritins with different inorganic cores, the fabrication of self-assembled arrays with the immobilized ferritin, and the electrochemical characterization of various core materials. Protein immobilization on the substrate is achieved by anchoring ferritins with dithiobis-N-succinimidyl propionate (DTSP). A reconstitution process of electrochemical site-specific biomineralization with a protein cage loads ferritins with different core materials such as Pt, Co, Mn, and Ni. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. The nano-sized metalcored ferritins on a gold substrate displayed a good electrochemical activity for the electron transport and storage, which is suitable for bioelectronics applications such as biofuel cell, bionanobattery, biosensors, etc. Keywords: Ferritin, immobilization, site-specific reconstitution, biomineralization, and bioelectronics

Ion Transport across Biological Membranes by Carborane-Capped Gold Nanoparticles.

PubMed

Grzelczak, Marcin P; Danks, Stephen P; Klipp, Robert C; Belic, Domagoj; Zaulet, Adnana; Kunstmann-Olsen, Casper; Bradley, Dan F; Tsukuda, Tatsuya; Viñas, Clara; Teixidor, Francesc; Abramson, Jonathan J; Brust, Mathias

2017-12-26

Carborane-capped gold nanoparticles (Au/carborane NPs, 2-3 nm) can act as artificial ion transporters across biological membranes. The particles themselves are large hydrophobic anions that have the ability to disperse in aqueous media and to partition over both sides of a phospholipid bilayer membrane. Their presence therefore causes a membrane potential that is determined by the relative concentrations of particles on each side of the membrane according to the Nernst equation. The particles tend to adsorb to both sides of the membrane and can flip across if changes in membrane potential require their repartitioning. Such changes can be made either with a potentiostat in an electrochemical cell or by competition with another partitioning ion, for example, potassium in the presence of its specific transporter valinomycin. Carborane-capped gold nanoparticles have a ligand shell full of voids, which stem from the packing of near spherical ligands on a near spherical metal core. These voids are normally filled with sodium or potassium ions, and the charge is overcompensated by excess electrons in the metal core. The anionic particles are therefore able to take up and release a certain payload of cations and to adjust their net charge accordingly. It is demonstrated by potential-dependent fluorescence spectroscopy that polarized phospholipid membranes of vesicles can be depolarized by ion transport mediated by the particles. It is also shown that the particles act as alkali-ion-specific transporters across free-standing membranes under potentiostatic control. Magnesium ions are not transported.

Continuous nanoparticle production by microfluidic-based emulsion, mixing and crystallization

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

Su, Y.-F.; Kim, H.; Kovenklioglu, S.

2007-09-15

BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles. BaSO{sub 4} nanoparticles in the size range of 15-100 nm were reactively precipitated within the confinement of an aqueous droplet which was coalesced from two separate aqueous droplets containing BaCl{sub 2} and (NH{sub 4}){sub 2}SO{sub 4} using a three T-junction micromixer configuration constructed with commercially available simple tubing and fitting supplies. Also, DPA nanoparticles of about 200 nm were crystallized by combining DPA+ethanol and watermore » droplets using the same micromixer configuration. - Graphical abstract: BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles.« less

Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy.

PubMed

Kang, Seounghun; Shin, Woojun; Choi, Myung-Ho; Ahn, Minchul; Kim, Young-Kwan; Kim, Seongchan; Min, Dal-Hee; Jang, Hongje

2018-06-22

Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructures-nanoshells, nanoframes, and porous nanoplates-were successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.

The design and application of fluorophore–gold nanoparticle activatable probes

PubMed Central

Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

2013-01-01

Fluorescence-based assays and detection techniques are among the most highly sensitive and popular biological tests for researchers. To match the needs of research and the clinic, detection limits and specificities need to improve, however. One mechanism is to decrease non-specific background signals, which is most efficiently done by increasing fluorescence quenching abilities. Reports in the literature of theoretical and experimental work have shown that metallic gold surfaces and nanoparticles are ultra-efficient fluorescence quenchers. Based on these findings, subsequent reports have described gold nanoparticle fluorescence-based activatable probes that were designed to increase fluorescence intensity based on a range of stimuli. In this way, these probes can detect and signify assorted biomarkers and changes in environmental conditions. In this review, we explore the various factors and theoretical models that affect gold nanoparticle fluorescence quenching, explore current uses of activatable probes, and propose an engineering approach for future development of fluorescence based gold nanoparticle activatable probes. PMID:21380462

Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition.

PubMed

Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; De Biasi, Federico; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

2017-07-13

The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which could explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs.

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

PubMed Central

Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

2012-01-01

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

Development of screening assays for nanoparticle toxicity assessment in human blood: preliminary studies with charged Au nanoparticles.

PubMed

Love, Sara A; Thompson, John W; Haynes, Christy L

2012-09-01

As nanoparticles have found increased use in both consumer and medical applications, corresponding increases in possible exposure to humans necessitate studies examining the impacts of these nanomaterials in biological systems. This article examines the effects of approximately 30-nm-diameter gold nanoparticles, with positively and negatively charged surface coatings in human blood. Here, we study the exposure effects, with up to 72 h of exposure to 5, 15, 25 and 50 µg/ml nanoparticles on hemolysis, reactive oxygen species (ROS) generation and platelet aggregation in subsets of cells from human blood. Assessing viability with hemolysis, results show significant changes in a concentration-dependent fashion. Rates of ROS generation were investigated using the dichlorofluorscein diacetate-based assay as ROS generation is a commonly suspected mechanism of nanoparticle toxicity; herein, ROS was not a significant factor. Optical monitoring of platelet aggregation revealed that none of the examined nanoparticles induced aggregation upon short-term exposure.

Microwave-assisted synthesis of triple-helical, collagen-mimetic lipopeptides

PubMed Central

Banerjee, Jayati; Hanson, Andrea J; Muhonen, Wallace W; Shabb, John B; Mallik, Sanku

2018-01-01

Collagen-mimetic peptides and lipopeptides are widely used as substrates for matrix degrading enzymes, as new biomaterials for tissue engineering, as drug delivery systems and so on. However, the preparation and subsequent purification of these peptides and their fatty-acid conjugates are really challenging. Herein, we report a rapid microwave-assisted, solid-phase synthetic protocol to prepare the fatty-acid conjugated, triple-helical peptides containing the cleavage site for the enzyme matrix metalloproteinase-9 (MMP-9). We employed a PEG-based resin as the solid support and the amino acids were protected with Fmoc- and tert-butyl groups. The amino acids were coupled at 50 °C (25 W of microwave power) for 5 min. The deprotection reactions were carried out at 75 °C (35 W of microwave power) for 3 min. Using this protocol, a peptide containing 23 amino acids was synthesized and then conjugated to stearic acid in 14 h. PMID:20057380

How Do Enzymes 'Meet' Nanoparticles and Nanomaterials?

PubMed

Chen, Ming; Zeng, Guangming; Xu, Piao; Lai, Cui; Tang, Lin

2017-11-01

Enzymes are fundamental biological catalysts responsible for biological regulation and metabolism. The opportunity for enzymes to 'meet' nanoparticles and nanomaterials is rapidly increasing due to growing demands for applications in nanomaterial design, environmental monitoring, biochemical engineering, and biomedicine. Therefore, understanding the nature of nanomaterial-enzyme interactions is becoming important. Since 2014, enzymes have been used to modify, degrade, or make nanoparticles/nanomaterials, while numerous nanoparticles/nanomaterials have been used as materials for enzymatic immobilization and biosensors and as enzyme mimicry. Among the various nanoparticles and nanomaterials, metal nanoparticles and carbon nanomaterials have received extensive attention due to their fascinating properties. This review provides an overview about how enzymes meet nanoparticles and nanomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bacterial exposure to metal-oxide nanoparticles: Methods, physical interactions, and biological effects

NASA Astrophysics Data System (ADS)

Horst, Allison Marie

Nanotechnology is a major endeavor of this century, with proposed applications in fields ranging from agriculture to energy to medicine. Nanoscale titanium dioxide (nano-TiO2) is among the most widely produced nanoparticles worldwide, and already exists in consumer products including impermanent personal care products and surface coatings. Inevitably, nano-TiO2 will be transported into the environment via consumer or industrial waste, where its effects on organisms are largely unknown. Out of concern for the possible ill-effects of nanoparticles in the environment, there is now a field of study in nanotoxicology. Bacteria are ideal organisms for nanotoxicology research because they are environmentally important, respond rapidly to intoxication, and provide evidence for effects in higher organisms. My doctoral research focuses on the effects and interactions of nano-TiO2 in aqueous systems with planktonic bacteria. This dissertation describes four projects and the outcomes of the research: (1) A discovery, using a combination of environmental- and cryogenic-scanning electron microscopy and dynamic light scattering (DLS), that initially agglomerated nano-TiO2 is dispersed upon bacterial contact, as nanoparticles preferentially sorbed to cell surfaces. (2) Establishment of a method to disperse nanoparticles in an aqueous culture medium for nanotoxicology studies. A combination of electrostatic repulsion, steric hindrance and sonication yielded a high initial level of nano-TiO2 dispersion (i.e. < 300 nm average agglomerate size) and reduced nanoparticle sedimentation. The approach is described in the context of general considerations for dispersion that are transferable to other nanoparticle and media chemistries. (3) Assessment and optimization of optically-based assays to simultaneously study effects of nanoparticles on bacterial membranes (membrane potential, membrane permeability, and electron transport chain function) and generation of reactive oxygen species. A

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its D,L-polylactide microparticle formulation.

PubMed

Bartolini, D; Piroddi, M; Tidei, C; Giovagnoli, S; Pietrella, D; Manevich, Y; Tew, K D; Giustarini, D; Rossi, R; Townsend, D M; Santi, C; Galli, F

2015-01-01

Catalytic properties and cellular effects of the glutathione peroxidase (GPx)-mimetic compound PhSeZnCl or its d,l-lactide polymer microencapsulation form (M-PhSeZnCl) were investigated and compared with the prototypical Se-organic compounds ebselen and diselenide (PhSe)2. PhSeZnCl was confirmed to catalyze the ping-pong reaction of GPx with higher Vmax than ebselen and (PhSe)2, but the catalytic efficiency calculated for the cosubstrates glutathione (GSH) and H2O2, and particularly the high reactivity against thiols (lowest KM for GSH in the series of test molecules), suggested poor biological applicability of PhSeZnCl as a GPx mimetic. Cytotoxicity of PhSeZnCl was demonstrated in various cancer cell lines via increased reactive oxygen species (ROS) generation, depletion of intracellular thiols, and induction of apoptosis. Experiments carried out in GSH S-transferase P (GSTP)-overexpressing K562 human erythroleukemia cells and in GSTP1-1-knockout murine embryonic fibroblasts (MEFs) demonstrated that this cytosolic enzyme represents a preferential target of the redox disturbances produced by this Se-compound with a key role in controlling H2O2 generation and the perturbation of stress/survival kinase signaling. Microencapsulation was adopted as a strategy to control the thiol reactivity and oxidative stress effects of PhSeZnCl, then assessing applications alternative to anticancer. The uptake of this "depowered" GPx-mimetic formulation, which occurred through an endocytosis-like mechanism, resulted in a marked reduction of cytotoxicity. In MCF-7 cells transfected with different allelic variants of GSTP, M-PhSeZnCl lowered the burst of cellular ROS induced by the exposure to extracellular H2O2, and the extent of this effect changed between the GSTP variants. Microencapsulation is a straightforward strategy to mitigate the toxicity of thiol-reactive Se-organic drugs that enhanced the antioxidant and cellular protective effects of PhSeZnCl. A mechanistic linkage of

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its d,l-polylactide microparticle formulation

PubMed Central

Bartolini, D.; Piroddi, M.; Tidei, C.; Giovagnoli, S.; Pietrella, D.; Manevich, Y.; Tew, K.D.; Giustarini, D.; Rossi, R.; Townsend, D.M.; Santi, C.; Galli, F.

2015-01-01

Catalytic properties and cellular effects of the glutathione peroxidase (GPx)-mimetic compound PhSeZnCl or its d,l-lactide polymer microencapsulation form (M-PhSeZnCl) were investigated and compared with the prototypical Se-organic compounds ebselen and diselenide (PhSe)2. PhSeZnCl was confirmed to catalyze the ping-pong reaction of GPx with higher Vmax than ebselen and (PhSe)2, but the catalytic efficiency calculated for the cosubstrates glutathione (GSH) and H2O2, and particularly the high reactivity against thiols (lowest KM for GSH in the series of test molecules), suggested poor biological applicability of PhSeZnCl as a GPx mimetic. Cytotoxicity of PhSeZnCl was demonstrated in various cancer cell lines via increased reactive oxygen species (ROS) generation, depletion of intracellular thiols, and induction of apoptosis. Experiments carried out in GSH S-transferase P (GSTP)-overexpressing K562 human erythroleukemia cells and in GSTP1-1-knockout murine embryonic fibroblasts (MEFs) demonstrated that this cytosolic enzyme represents a preferential target of the redox disturbances produced by this Se-compound with a key role in controlling H2O2 generation and the perturbation of stress/survival kinase signaling. Microencapsulation was adopted as a strategy to control the thiol reactivity and oxidative stress effects of PhSeZnCl, then assessing applications alternative to anticancer. The uptake of this “depowered” GPx-mimetic formulation, which occurred through an endocytosis-like mechanism, resulted in a marked reduction of cytotoxicity. In MCF-7 cells transfected with different allelic variants of GSTP, M-PhSeZnCl lowered the burst of cellular ROS induced by the exposure to extracellular H2O2, and the extent of this effect changed between the GSTP variants. Microencapsulation is a straightforward strategy to mitigate the toxicity of thiol-reactive Se-organic drugs that enhanced the antioxidant and cellular protective effects of PhSeZnCl. A mechanistic linkage

Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS-PAGE and LC-MS.

PubMed

Gossmann, R; Fahrländer, E; Hummel, M; Mulac, D; Brockmeyer, J; Langer, K

2015-06-01

The behavior of nanosized drug carrier systems under cell culture conditions and therefore also the destiny in the body are highly influenced by the protein corona, which is formed upon entering a biological environment. Some of the adsorbed proteins, named opsonins, lead to a shortened plasma circulation half-life of the nanoparticles. Others are attributed to promote the transport of nanoparticles into other compartments of the body, just to mention two examples. Hence, detailed knowledge concerning the composition of the protein corona is of great importance. The aim of this work was to investigate the influence of the nanoparticle starting material and the surface modification on the composition of the adsorbed serum proteins in a cell culture environment. Therefore, positively charged nanoparticles based on the biodegradable polymer poly(dl-lactide-co-glycolide) (PLGA) stabilized with didodecyldimethylammonium bromide (DMAB) and negatively charged nanoparticles based on human serum albumin (HSA) were prepared and modified with hydrophilic polymers. By incubating the nanoparticles with fetal bovine serum (FBS) the adsorption of serum proteins on the colloidal system was investigated. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) a semi-quantitative analysis of the protein corona was performed and after enzymatic in-solution-digestion the adsorbed proteins were identified using high resolution LC-MS. Our study accentuates the influence of the core material, surface charge, and surface modification on the amount and nature of the adsorbed proteins. The combination of SDS-PAGE and LC-MS turns out to be a simple and reliable method to investigate the protein corona of nanoparticles. Copyright © 2015 Elsevier B.V. All rights reserved.