Airspace Dimension Assessment with nanoparticles reflects lung density as quantified by MRI

PubMed Central

Jakobsson, Jonas K; Löndahl, Jakob; Olsson, Lars E; Diaz, Sandra; Zackrisson, Sophia; Wollmer, Per

2018-01-01

Background Airspace Dimension Assessment with inhaled nanoparticles is a novel method to determine distal airway morphology. This is the first empirical study using Airspace Dimension Assessment with nanoparticles (AiDA) to estimate distal airspace radius. The technology is relatively simple and potentially accessible in clinical outpatient settings. Method Nineteen never-smoking volunteers performed nanoparticle inhalation tests at multiple breath-hold times, and the difference in nanoparticle concentration of inhaled and exhaled gas was measured. An exponential decay curve was fitted to the concentration of recovered nanoparticles, and airspace dimensions were assessed from the half-life of the decay. Pulmonary tissue density was measured using magnetic resonance imaging (MRI). Results The distal airspace radius measured by AiDA correlated with lung tissue density as measured by MRI (ρ = −0.584; p = 0.0086). The linear intercept of the logarithm of the exponential decay curve correlated with forced expiratory volume in one second (FEV1) (ρ = 0.549; p = 0.0149). Conclusion The AiDA method shows potential to be developed into a tool to assess conditions involving changes in distal airways, eg, emphysema. The intercept may reflect airway properties; this finding should be further investigated.

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging.

PubMed

Mulder, Willem J M; Strijkers, Gustav J; van Tilborg, Geralda A F; Griffioen, Arjan W; Nicolay, Klaas

2006-02-01

In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed. 2006 John Wiley & Sons, Ltd.

Engineering Gd-loaded nanoparticles to enhance MRI sensitivity via T1 shortening

NASA Astrophysics Data System (ADS)

Bruckman, Michael A.; Yu, Xin; Steinmetz, Nicole F.

2013-11-01

Magnetic resonance imaging (MRI) is a noninvasive imaging technique capable of obtaining high-resolution anatomical images of the body. Major drawbacks of MRI are the low contrast agent sensitivity and inability to distinguish healthy tissue from diseased tissue, making early detection challenging. To address this technological hurdle, paramagnetic contrast agents have been developed to increase the longitudinal relaxivity, leading to an increased signal-to-noise ratio. This review focuses on methods and principles that enabled the design and engineering of nanoparticles to deliver contrast agents with enhanced ionic relaxivities. Different engineering strategies and nanoparticle platforms will be compared in terms of their manufacturability, biocompatibility properties, and their overall potential to make an impact in clinical MR imaging.

Iron oxide nanoparticles stabilized with dendritic polyglycerols as selective MRI contrast agents

NASA Astrophysics Data System (ADS)

Nordmeyer, Daniel; Stumpf, Patrick; Gröger, Dominic; Hofmann, Andreas; Enders, Sven; Riese, Sebastian B.; Dernedde, Jens; Taupitz, Matthias; Rauch, Ursula; Haag, Rainer; Rühl, Eckart; Graf, Christina

2014-07-01

Monodisperse small iron oxide nanoparticles functionalized with dendritic polyglycerol (dPG) or dendritic polyglycerol sulfate (dPGS) are prepared. They are highly stable in aqueous solutions as well as physiological media. In particular, oleic acid capped iron oxide particles (core diameter = 11 +/- 1 nm) were modified by a ligand exchange process in a one pot synthesis with dPG and dPGS bearing phosphonate as anchor groups. Dynamic light scattering measurements performed in water and different biological media demonstrate that the hydrodynamic diameter of the particles is only slightly increased by the ligand exchange process resulting in a final diameter of less than 30 nm and that the particles are stable in these media. It is also revealed by magnetic resonance studies that their magnetic relaxivity is reduced by the surface modification but it is still sufficient for high contrast magnetic resonance imaging (MRI). Additionally, incubation of dPGS functionalized iron oxide nanoparticles with human umbilical vein endothelial cells showed a 50% survival at 85 nM (concentration of nanoparticles). Surface plasmon resonance (SPR) studies demonstrate that the dPGS functionalized iron oxide nanoparticles inhibit L-selectin ligand binding whereas the particles containing only dPG do not show this effect. Experiments in a flow chamber with human myelogenous leukemia cells confirmed L-selectin inhibition of the dPGS functionalized iron oxide nanoparticles and with that the L-selectin mediated leukocyte adhesion. These results indicate that dPGS functionalized iron oxide nanoparticles are a promising contrast agent for inflamed tissue probed by MRI.Monodisperse small iron oxide nanoparticles functionalized with dendritic polyglycerol (dPG) or dendritic polyglycerol sulfate (dPGS) are prepared. They are highly stable in aqueous solutions as well as physiological media. In particular, oleic acid capped iron oxide particles (core diameter = 11 +/- 1 nm) were modified by a

Non-invasive mapping of deep-tissue lymph nodes in live animals using a multimodal PET/MRI nanoparticle

NASA Astrophysics Data System (ADS)

Thorek, Daniel L. J.; Ulmert, David; Diop, Ndeye-Fatou M.; Lupu, Mihaela E.; Doran, Michael G.; Huang, Ruimin; Abou, Diane S.; Larson, Steven M.; Grimm, Jan

2014-01-01

The invasion status of tumour-draining lymph nodes (LNs) is a critical indicator of cancer stage and is important for treatment planning. Clinicians currently use planar scintigraphy and single-photon emission computed tomography (SPECT) with 99mTc-radiocolloid to guide biopsy and resection of LNs. However, emerging multimodality approaches such as positron emission tomography combined with magnetic resonance imaging (PET/MRI) detect sites of disease with higher sensitivity and accuracy. Here we present a multimodal nanoparticle, 89Zr-ferumoxytol, for the enhanced detection of LNs with PET/MRI. For genuine translational potential, we leverage a clinical iron oxide formulation, altered with minimal modification for radiolabelling. Axillary drainage in naive mice and from healthy and tumour-bearing prostates was investigated. We demonstrate that 89Zr-ferumoxytol can be used for high-resolution tomographic studies of lymphatic drainage in preclinical disease models. This nanoparticle platform has significant translational potential to improve preoperative planning for nodal resection and tumour staging.

Synthesis and characterization of superparamagnetic iron oxide nanoparticles as calcium-responsive MRI contrast agents

NASA Astrophysics Data System (ADS)

Xu, Pengfei; Shen, Zhiwei; Zhang, Baolin; Wang, Jun; Wu, Renhua

2016-12-01

Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca2+) using magnetic resonance imaging (MRI). Here we prepared calcium-responsive SPIONs for MRI, formed by combining poly(ethylene glycol) (PEG) and polyethylenimine (PEI) coated iron oxide nanoparticle (PEI/PEG-SPIONs) contrast agents with the straightforward calcium-sensing compound EGTA (ethylene glycol tetraacetic acid). EGTA was conjugated onto PEI/PEG-SPIONs using EDC/sulfo-NHS method. EGTA-SPIONs were characterized using TEM, XPS, DSL, TGA and SQUIID. DSL results show that the SPIONs aggregate in the presence of Ca2+. MRI analyses indicate that the water proton T2 relaxation rates in HEPES suspensions of the EGTA-SPIONs significantly increase with the calcium concentration because the SPIONs aggregate in the presence of Ca2+. The T2 values decreased 25% when Ca2+ concentration decreased from 1.2 to 0.8 mM. The aggregation of EGTA-SPIONs could be reversed by EDTA. EGTA-SPIONs have potential as smart contrast agents for Ca2+-sensitive MRI.

Convection-enhanced delivery of maghemite nanoparticles: Increased efficacy and MRI monitoring

PubMed Central

Perlstein, Benny; Ram, Zvi; Daniels, Dianne; Ocherashvilli, Aharon; Roth, Yiftach; Margel, Shlomo; Mardor, Yael

2008-01-01

Convection-enhanced drug delivery (CED) is a novel approach to delivering drugs into brain tissue. Drugs are delivered continuously via a catheter, enabling large volume distributions of high drug concentrations with minimum systemic toxicity. Previously we demonstrated that CED formation/extent of small molecules may be significantly improved by increasing infusate viscosities. In this study we show that the same methodology can be applied to monodispersed maghemite nanoparticles (MNPs). For this purpose we used a normal rat brain model and performed CED of MNPs over short infusion times. By adding 3% sucrose or 3%–6% polyethylene glycol (PEG; molecular weight 400) to saline containing pristine MNPs, we increased infusate viscosity and obtained increased CED efficacy. Further, we show that CED of dextran-coated MNPs (dextran-MNPs) resulted in increased efficacy over pristine MNPs (p < 0.007). To establish the use of MRI for reliable depiction of MNP distribution, CED of fluorescent dextran-MNPs was performed, demonstrating a significant correlation between the distributions as depicted by MRI and spectroscopic images (r2 = 0.74, p < 0.0002). MRI follow-up showed that approximately 80%–90% of the dextran-MNPs were cleared from the rat brain within 40 days of CED; the rest remained in the brain for more than 4 months. MNPs have been tested for applications such as targeted drug delivery and controlled drug release and are clinically used as a contrast agent for MRI. Thus, combining the CED method with the advantages of MNPs may provide a powerful tool to treat and monitor brain tumors. PMID:18316474

Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.

PubMed

Sweeney, Sean K; Luo, Yi; O'Donnell, Michael A; Assouline, Jose

Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm. To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent

Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats

NASA Astrophysics Data System (ADS)

Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

2016-04-01

The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate ( r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM-1 s-1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly

Multifunctional rare-Earth vanadate nanoparticles: luminescent labels, oxidant sensors, and MRI contrast agents.

PubMed

Abdesselem, Mouna; Schoeffel, Markus; Maurin, Isabelle; Ramodiharilafy, Rivo; Autret, Gwennhael; Clément, Olivier; Tharaux, Pierre-Louis; Boilot, Jean-Pierre; Gacoin, Thierry; Bouzigues, Cedric; Alexandrou, Antigoni

2014-11-25

Collecting information on multiple pathophysiological parameters is essential for understanding complex pathologies, especially given the large interindividual variability. We report here multifunctional nanoparticles which are luminescent probes, oxidant sensors, and contrast agents in magnetic resonance imaging (MRI). Eu(3+) ions in an yttrium vanadate matrix have been demonstrated to emit strong, nonblinking, and stable luminescence. Time- and space-resolved optical oxidant detection is feasible after reversible photoreduction of Eu(3+) to Eu(2+) and reoxidation by oxidants, such as H2O2, leading to a modulation of the luminescence emission. The incorporation of paramagnetic Gd(3+) confers in addition proton relaxation enhancing properties to the system. We synthesized and characterized nanoparticles of either 5 or 30 nm diameter with compositions of GdVO4 and Gd0.6Eu0.4VO4. These particles retain the luminescence and oxidant detection properties of YVO4:Eu. Moreover, the proton relaxivity of GdVO4 and Gd0.6Eu0.4VO4 nanoparticles of 5 nm diameter is higher than that of the commercial Gd(3+) chelate compound Dotarem at 20 MHz. Nuclear magnetic resonance dispersion spectroscopy showed a relaxivity increase above 10 MHz. Complexometric titration indicated that rare-earth leaching is negligible. The 5 nm nanoparticles injected in mice were observed with MRI to concentrate in the liver and the bladder after 30 min. Thus, these multifunctional rare-earth vanadate nanoparticles pave the way for simultaneous optical and magnetic resonance detection, in particular, for in vivo localization evolution and reactive oxygen species detection in a broad range of physiological and pathophysiological conditions.

An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors.

PubMed

Karageorgis, Anastassia; Dufort, Sandrine; Sancey, Lucie; Henry, Maxime; Hirsjärvi, Samuli; Passirani, Catherine; Benoit, Jean-Pierre; Gravier, Julien; Texier, Isabelle; Montigon, Olivier; Benmerad, Mériem; Siroux, Valérie; Barbier, Emmanuel L; Coll, Jean-Luc

2016-02-19

Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines.

Facile integration of multiple magnetite nanoparticles for theranostics combining efficient MRI and thermal therapy

NASA Astrophysics Data System (ADS)

Huang, Guoming; Zhu, Xianglong; Li, Hui; Wang, Lirong; Chi, Xiaoqin; Chen, Jiahe; Wang, Xiaomin; Chen, Zhong; Gao, Jinhao

2015-01-01

Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned that such IO/GO-COOH nanocomposites combining efficient MRI and photothermal therapy hold great promise in theranostic applications.Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned

Receptor-Targeted Nanoparticles for In Vivo Imaging of Breast Cancer

PubMed Central

Yang, Lily; Peng, Xiang-Hong; Wang, Y. Andrew; Wang, Xiaoxia; Cao, Zehong; Ni, Chunchun; Karna, Prasanthi; Zhang, Xinjian; Wood, William C.; Gao, Xiaohu; Nie, Shuming; Mao, Hui

2009-01-01

Purpose Cell surface receptor-targeted magnetic iron oxide (IO) nanoparticles provide molecular magnetic resonance imaging (MRI) contrast agents for improving specificity of the detection of human cancer. Experimental design The present study reports the development of a novel targeted IO nanoparticle using a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator conjugated to IO nanoparticles (ATF-IO). This nanoparticle targets urokinase plasminogen activator receptor (uPAR), which is overexpressed in breast cancer tissues. Results ATF-IO nanoparticles are able to specifically bind to and be internalized by uPAR-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing subcutaneous and intraperitoneal mammary tumors leads to the accumulation of the particles in tumors, generating a strong MRI contrast detectable by a clinical MRI scanner at a field strength of 3 Tesla. Target specificity of ATF-IO nanoparticles demonstrated by in vivo MRI is further confirmed by near infrared (NIR) fluorescence imaging of the mammary tumors using NIR dye-labeled ATF peptides conjugated to IO nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared to those receiving non-targeted IO nanoparticles. Conclusions Our results suggest that uPAR-targeted ATF-IO nanoparticles have potential as molecularly-targeted, dual modality imaging agents for in vivo imaging of breast cancer. PMID:19584158

Theranostic gold-magnetite hybrid nanoparticles for MRI-guided radiosensitization.

PubMed

Maniglio, D; Benetti, F; Minati, L; Jovicich, J; Valentini, A; Speranza, G; Migliaresi, C

2018-08-03

The main limitation of drug-enhanced radiotherapy concerns the difficulty to evaluate the effectiveness of cancer targeting after drug administration hindering the standardization of therapies based on current radiosensitizing compounds. The challenge regards the development of systems able to combine imaging and radiotherapy enhancement in order to perform highly reliable cancer theragnosis. For these reasons, gold-magnetite hybrid nanoparticles (H-NPs) are proposed as innovative theranostic nanotools for imaging-guided radiosensitization in cancer treatment. In this work we propose a novel method for the synthesis of hydrophilic and superparamagnetic Tween20-stabilized gold-magnetite H-NPs. Morphology and chemical composition of nanoparticles were assessed by transmission electron microscopy, x-ray diffraction analysis and ion-coupled plasma optical emission spectroscopy. Colloidal stability and magnetic properties of nanoparticles were determined by dynamic light scattering and magnetometry. The potentialities of H-NPs for magnetic resonance imaging were studied using a human 4T-MRI scanner. Nanoparticles were proven to induce concentration-dependent contrast enhancement in T2*-weighted MR-images. The cytotoxicity, the cellular uptake and the radiosensitization activity of H-NPs were investigated in human osteosarcoma MG63 cell cultures and murine 3T3 fibroblasts, using specific bioassays and laser scanning confocal microscopy. H-NPs did not exhibit significant toxicity and were demonstrated to be internalized by cells. A significant x-ray enhancement at specific H-NPs exposure concentrations was evidenced on MG63 cell line.

An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors

PubMed Central

Karageorgis, Anastassia; Dufort, Sandrine; Sancey, Lucie; Henry, Maxime; Hirsjärvi, Samuli; Passirani, Catherine; Benoit, Jean-Pierre; Gravier, Julien; Texier, Isabelle; Montigon, Olivier; Benmerad, Mériem; Siroux, Valérie; Barbier, Emmanuel L.; Coll, Jean-Luc

2016-01-01

Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines. PMID:26892874

Ultrasmall water-soluble metal-iron oxide nanoparticles as T1-weighted contrast agents for magnetic resonance imaging.

PubMed

Zeng, Leyong; Ren, Wenzhi; Zheng, Jianjun; Cui, Ping; Wu, Aiguo

2012-02-28

Using an improved hydrolysis method of inorganic salts assisted with water-bath incubation, ultrasmall water-soluble metal-iron oxide nanoparticles (including Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles) were synthesized in aqueous solutions, which were used as T(1)-weighted contrast agents for magnetic resonance imaging (MRI). The morphology, structure, MRI relaxation properties and cytotoxicity of the as-prepared metal-iron oxide nanoparticles were characterized, respectively. The results showed that the average sizes of nanoparticles were about 4 nm, 4 nm and 5 nm for Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles, respectively. Moreover, the nanoparticles have good water dispersibility and low cytotoxicity. The MRI test showed the strong T(1)-weighted, but the weak T(2)-weighted MRI performance of metal-iron oxide nanoparticles. The high T(1)-weighted MRI performance can be attributed to the ultrasmall size of metal-iron oxide nanoparticles. Therefore, the as-prepared metal-iron oxide nanoparticles with good water dispersibility and ultrasmall size can have potential applications as T(1)-weighted contrast agent materials for MRI.

Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model

PubMed Central

Hall, Sarah; Xia, Xin-Rui; Schwarz, Tobias

2017-01-01

Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE2 were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function, which could

Disruptive chemical doping in a ferritin-based iron oxide nanoparticle to decrease r2 and enhance detection with T1-weighted MRI.

PubMed

Clavijo Jordan, M Veronica; Beeman, Scott C; Baldelomar, Edwin J; Bennett, Kevin M

2014-01-01

Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity (r2). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r2. While sensitive, they can have limited in vivo detection due to a number of constraints with T2 or T2*-weighted imaging. T1-weighted imaging is often preferred for molecular MRI, but most T1-shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T2 and limit the range of concentrations detectable with T1-weighting. Here we used tungsten and iron deposition to form doped iron oxide crystals inside the apoferritin cavity to form a WFe nanoparticle with a disordered crystal and un-coupled atomic magnetic moments. The atomic magnetic moments were thus localized, resulting in a principally paramagnetic nanoparticle. The WFe nanoparticles had no coercivity or saturation magnetization at 5 K and sweeping up to ± 20,000 Oe, while native ferritin had a coercivity of 3000 Oe and saturation at ± 20,000 Oe. This tungsten-iron crystal paramagnetism resulted in an increased WFe particle longitudinal relaxivity (r1) of 4870 mm(-1) s(-1) and a reduced transverse relaxivity (r2) of 9076 mm(-1) s(-1) compared with native ferritin. The accumulation of the particles was detected with T1-weighted MRI in concentrations from 20 to 400 nm in vivo, both injected in the rat brain and targeted to the rat kidney glomerulus. The WFe apoferritin nanoparticles were not cytotoxic up to 700 nm particle concentrations, making them potentially important for targeted molecular MRI. Copyright © 2014 John Wiley & Sons, Ltd.

Tumor-Targeting Multifunctional Rattle-Type Theranostic Nanoparticles for MRI/NIRF Bimodal Imaging and Delivery of Hydrophobic Drugs.

PubMed

Jiao, Yunfeng; Sun, Yangfei; Tang, Xiaoling; Ren, Qingguang; Yang, Wuli

2015-04-24

The development of theranostic systems capable of diagnosis, therapy, and target specificity is considerably significant for accomplishing personalized medicine. Here, a multifunctional rattle-type nanoparticle (MRTN) as an effective biological bimodal imaging and tumor-targeting delivery system is fabricated, and an enhanced loading ability of hydrophobic anticancer drug (paclitaxel) is also realized. The rattle structure with hydrophobic Fe3 O4 as the inner core and mesoporous silica as the shell is obtained by one-step templates removal process, and the size of interstitial hollow space can be easily adjusted. The Fe3 O4 core with hydrophobic poly(tert-butyl acrylate) (PTBA) chains on the surface is not only used as a magnetic resonance imaging (MRI) agent, but contributes to improving hydrophobic drug loading amount. Transferrin (Tf) and a near-infrared fluorescent dye (Cy 7) are successfully modified on the surface of the nanorattle to increase the ability of near-infrared fluorescence (NIRF) imaging and tumor-targeting specificity. In vivo studies show the selective accumulation of MRTN in tumor tissues by Tf-receptor-mediated endocytosis. More importantly, paclitaxel-loaded MRTN shows sustained release character and higher cytotoxicity than the free paclitaxel. This theranostic nanoparticle as an effective MRI/NIRF bimodal imaging probe and drug delivery system shows great potential in cancer diagnosis and therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

A simple polyol-free synthesis route to Gd2O3 nanoparticles for MRI applications: an experimental and theoretical study

NASA Astrophysics Data System (ADS)

Ahrén, Maria; Selegård, Linnéa; Söderlind, Fredrik; Linares, Mathieu; Kauczor, Joanna; Norman, Patrick; Käll, Per-Olov; Uvdal, Kajsa

2012-08-01

Chelated gadolinium ions, e.g., Gd-DTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4-5-nm-sized Gd2O3 nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r 1 and r 2 values almost as high as those for free Gd3+ ions in water. The Gd2O3 nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.

Thermal- and pH-Dependent Size Variable Radical Nanoparticles and Its Water Proton Relaxivity for Metal-Free MRI Functional Contrast Agents.

PubMed

Morishita, Kosuke; Murayama, Shuhei; Araki, Takeru; Aoki, Ichio; Karasawa, Satoru

2016-09-16

For development of the metal-free MRI contrast agents, we prepared the supra-molecular organic radical, TEMPO-UBD, carrying TEMPO radical, as well as the urea, alkyl group, and phenyl ring, which demonstrate self-assembly behaviors using noncovalent bonds in an aqueous solution. In addition, TEMPO-UBD has the tertiary amine and the oligoethylene glycol chains (OEGs) for the function of pH and thermal responsiveness. By dynamic light scattering and transmission electron microscopy imaging, the resulting self-assembly was seen to form the spherical nanoparticles 10-150 nm in size. On heating, interestingly, the nanoparticles showed a lower critical solution temperature (LCST) behavior having two-step variation. This double-LCST behavior is the first such example among the supra-molecules. To evaluate of the ability as MRI contrast agents, the values of proton ((1)H) longitudinal relaxivity (r1) were determined using MRI apparatus. In conditions below and above CAC at pH 7.0, the distinguishable r1 values were estimated to be 0.17 and 0.21 mM(-1) s(1), indicating the suppression of fast tumbling motion of TEMPO moiety in a nanoparticle. Furthermore, r1 values became larger in the order of pH 7.0 > 9.0 > 5.0. Those thermal and pH dependencies indicated the possibility of metal-fee MRI functional contrast agents in the future.

Cyclodextrin-Based Magnetic Nanoparticles for Cancer Therapy

PubMed Central

Jędrzak, Artur; Szutkowski, Kosma; Grześkowiak, Bartosz F.; Markiewicz, Roksana; Jesionowski, Teofil; Jurga, Stefan

2018-01-01

Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-β-cyclodextrin (SH-βCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro. Moreover, our material exhibits improved T2 contrast properties, which have been verified using Carr-Purcell-Meiboom-Gill pulse sequence and MRI Spin-Echo imaging of the nanoparticles dispersed in the agarose gel phantoms. Therefore, the presented results cast new light on the preparation of polydopamine-based magnetic theranostic nanomaterials, as well as on the proper methodology for investigation of magnetic nanoparticles in high field MRI experiments. The prepared material is a robust theranostic nanoasystem with great potential in nanomedicine. PMID:29547559

Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents

DOE PAGES

Malyutin, Andrey G.; Easterday, Rosemary; Lozovyy, Yaroslav; ...

2014-12-15

Here, for the first time, we demonstrate formation of virus-like nanoparticles (VNPs) utilizing gold-coated iron oxide nanoparticles as cores and capsidprotein of brome mosaic virus (BMV) or hepatitis B virus (HBV) as shells. Further, utilizing cryo-electron microscopy and single particle methods, we are able to show that the BMV coat on VNPs assembles into a structure very close to that of a native virion. This is a consequence of an optimal iron oxide NP size (~11 nm) fitting the virus cavity and an ultrathin gold layer on the maghemite cores, which allows for utilization of SH-(CH 2) 11-(CH 2-CH 2-O)more » 4-OCH 2-COOH as capping molecules to provide sufficient stability, charge density, and small form factor. MRI studies show unique relaxivity ratios that diminish only slightly with gold coating. In conclusion, a virus protein coating of a magnetic core mimicking the wild-type virus makes these VNPs a versatile platform for biomedical applications.« less

Multimodality PET/MRI agents targeted to activated macrophages.

PubMed

Tu, Chuqiao; Ng, Thomas S C; Jacobs, Russell E; Louie, Angelique Y

2014-02-01

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-(64)Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-(64)Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM(-1) s(-1), and an r 2 relaxivity of 83.9 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-(64)Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.

Au Nanocage Functionalized with Ultra-small Fe3O4 Nanoparticles for Targeting T1-T2Dual MRI and CT Imaging of Tumor

NASA Astrophysics Data System (ADS)

Wang, Guannan; Gao, Wei; Zhang, Xuanjun; Mei, Xifan

2016-06-01

Diagnostic approaches based on multimodal imaging of clinical noninvasive imaging (eg. MRI/CT scanner) are highly developed in recent years for accurate selection of the therapeutic regimens in critical diseases. Therefore, it is highly demanded in the development of appropriate all-in-one multimodal contrast agents (MCAs) for the MRI/CT multimodal imaging. Here a novel ideal MCAs (F-AuNC@Fe3O4) were engineered by assemble Au nanocages (Au NC) and ultra-small iron oxide nanoparticles (Fe3O4) for simultaneous T1-T2dual MRI and CT contrast imaging. In this system, the Au nanocages offer facile thiol modification and strong X-ray attenuation property for CT imaging. The ultra-small Fe3O4 nanoparticles, as excellent contrast agent, is able to provide great enhanced signal of T1- and T2-weighted MRI (r1 = 6.263 mM-1 s-1, r2 = 28.117 mM-1 s-1) due to their ultra-refined size. After functionalization, the present MCAs nanoparticles exhibited small average size, low aggregation and excellent biocompatible. In vitro and In vivo studies revealed that the MCAs show long-term circulation time, renal clearance properties and outstanding capability of selective accumulation in tumor tissues for simultaneous CT imaging and T1- and T2-weighted MRI. Taken together, these results show that as-prepared MCAs are excellent candidates as MRI/CT multimodal imaging contrast agents.

High potential of Mn-doped ZnS nanoparticles with different dopant concentrations as novel MRI contrast agents: synthesis and in vitro relaxivity studies

NASA Astrophysics Data System (ADS)

Jahanbin, Tania; Gaceur, Meriem; Gros-Dagnac, Hélène; Benderbous, Soraya; Merah, Souad Ammar

2015-06-01

Over several decades, metal-doped quantum dots (QDs) with core-shell structure have been studied as dual probes: fluorescence and magnetic resonance imaging (MRI) probes (Dixit et al., Mater Lett 63(30):2669-2671, 2009). However, metal-doped nanoparticles, in which the majority of metal ions are close to the surface, can affect their efficacy as MRI contrast agents (CAs). In this context, herein the high potential of synthesized Mn-doped ZnS QDs via polyol method as imaging probe is demonstrated. The mean diameters of QDs were measured via transmission electron microscopy (TEM) and X-ray diffraction (XRD). Optical and magnetic properties of MnZnS nanoparticles were characterized using fluorescence spectroscopy and super quanducting interference devices magnetometer and electron paramagnetic resonance system, respectively. T1- and T2-weighted images of nanoparticles in aqueous solution were acquired from spin-echo sequences at 3 T. From TEM images and XRD spectra of the prepared nanoparticles, it is observed that the average diameter of particles does not significantly change with Mn dopant content ( 1.6-1.9 nm). All three samples exhibit broad blue emission under UV light excitation. According to the MRI studies, MnZnS nanoparticles generate strong T1 contrast enhancement (bright T1-weighted images) at the low concentration (<0.1 mM). The MnZnS nanoparticles exhibit the high longitudinal ( r 1) relaxivity that increases from 20.34 to 75.5 mM-1 s-1 with the Mn dopant contents varying between 10 and 30 %. Strong signal intensity on T1-weighted images and high r 1 with {r2 }/{r_{1 }} ≈ 1 can demonstrate the high potential of the synthesized Mn:ZnS nanoparticles, which can serve as an effective T1 CA.

Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS

PubMed Central

Waters, Emily A; Chen, Junjie; Allen, John S; Zhang, Huiying; Lanza, Gregory M; Wickline, Samuel A

2008-01-01

Background Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of ανβ3 integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets. Methods New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with ανβ3 integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition in vivo of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and 19F MRS was performed at 11.7T. Integrated 19F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with ανβ3 integrin targeted PFC nanoparticles, 19F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry. Results Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001). Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles reduced the fluorine signal by 42% due to competitive inhibition, to a level not significantly different from control

Role of Intra-operative MRI (iMRI) in Improving Extent of Resection and Survival in Patients with Glioblastoma Multiforme.

PubMed

Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-07-01

Multiple intraoperative aids have been introduced to improve the extent of resection (EOR) in Glioblastoma Multiforme (GBM) patients, avoiding any new neurological deficits. Intraoperative MRI (iMRI) has been debated for its utility and cost for nearly two decades in neurosurgical literature. Review of literature suggests improved EOR in GBM patients who underwent iMRI assisted surgical resections leading to higher overall survival (OS) and progression free survival (PFS). iMRI provides real time intraoperative imaging with reasonable quality. Higher risk for new postoperative deficits with increased EOR is not reported in any study using iMRI. The level of evidence regarding prognostic benefits of iMRI is still of low quality..

Combining diffusion-weighted MRI with Gd-EOB-DTPA-enhanced MRI improves the detection of colorectal liver metastases.

PubMed

Koh, D-M; Collins, D J; Wallace, T; Chau, I; Riddell, A M

2012-07-01

To compare the diagnostic accuracy of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, diffusion-weighted MRI (DW-MRI) and a combination of both techniques for the detection of colorectal hepatic metastases. 72 patients with suspected colorectal liver metastases underwent Gd-EOB-DTPA MRI and DW-MRI. Images were retrospectively reviewed with unenhanced T(1) and T(2) weighted images as Gd-EOB-DTPA image set, DW-MRI image set and combined image set by two independent radiologists. Each lesion detected was scored for size, location and likelihood of metastasis, and compared with surgery and follow-up imaging. Diagnostic accuracy was compared using receiver operating characteristics and interobserver agreement by kappa statistics. 417 lesions (310 metastases, 107 benign) were found in 72 patients. For both readers, diagnostic accuracy using the combined image set was higher [area under the curve (Az)=0.96, 0.97] than Gd-EOB-DTPA image set (Az=0.86, 0.89) or DW-MRI image set (Az=0.93, 0.92). Using combined image set improved identification of liver metastases compared with Gd-EOB-DTPA image set (p<0.001) or DW-MRI image set (p<0.001). There was very good interobserver agreement for lesion classification (κ=0.81-0.88). Combining DW-MRI with Gd-EOB-DTPA-enhanced T(1) weighted MRI significantly improved the detection of colorectal liver metastases.

Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer's disease mice using magnetic resonance imaging (MRI).

PubMed

Cheng, Kwok Kin; Chan, Pui Shan; Fan, Shujuan; Kwan, Siu Ming; Yeung, King Lun; Wáng, Yì-Xiáng J; Chow, Albert Hee Lum; Wu, Ed X; Baum, Larry

2015-03-01

Diagnosis of Alzheimer's disease (AD) can be performed with the assistance of amyloid imaging. The current method relies on positron emission tomography (PET), which is expensive and exposes people to radiation, undesirable features for a population screening method. Magnetic resonance imaging (MRI) is cheaper and is not radioactive. Our approach uses magnetic nanoparticles (MNPs) made of superparamagnetic iron oxide (SPIO) conjugated with curcumin, a natural compound that specifically binds to amyloid plaques. Coating of curcumin-conjugated MNPs with polyethylene glycol-polylactic acid block copolymer and polyvinylpyrrolidone by antisolvent precipitation in a multi-inlet vortex mixer produces stable and biocompatible curcumin magnetic nanoparticles (Cur-MNPs) with mean diameter <100 nm. These nanoparticles were visualized by transmission electron microscopy and atomic force microscopy, and their structure and chemistry were further characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and Fourier transform infrared spectroscopy. Cur-MNPs exhibited no cytotoxicity in either Madin-Darby canine kidney (MDCK) or differentiated human neuroblastoma cells (SH-SY5Y). The Papp of Cur-MNPs was 1.03 × 10(-6) cm/s in an in vitro blood-brain barrier (BBB) model. Amyloid plaques could be visualized in ex vivo T2*-weighted magnetic resonance imaging (MRI) of Tg2576 mouse brains after injection of Cur-MNPs, and no plaques could be found in non-transgenic mice. Immunohistochemical examination of the mouse brains revealed that Cur-MNPs were co-localized with amyloid plaques. Thus, Cur-MNPs have the potential for non-invasive diagnosis of AD using MRI. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diffusion and clearance of superparamagnetic iron oxide nanoparticles infused into the rat striatum studied by MRI and histochemical techniques

NASA Astrophysics Data System (ADS)

Wang, F. H.; Kim, D. K.; Yoshitake, T.; Johansson, S. M.; Bjelke, B.; Muhammed, M.; Kehr, J.

2011-01-01

The purpose of the present study was to investigate, by MRI and histochemical techniques, the diffusion and clearance abilities of superparamagnetic iron oxide nanoparticles (SPION) coated with dextran (Dextran-SPION) and gold (Au-SPION) following their local infusions into the rat brain. In separate groups of anesthetized rats, the Dextran-SPION and Au-SPION were infused at concentrations of 0.01, 0.1, 1 and 5 µg Fe/0.5 µl and at the flow rate of 0.5 µl min - 1 into the left and right striata, respectively. Repetitive T2-weighted spin-echo MRI scans were performed at time intervals of 1, 6, 12, 24, 48, 72 h, and one, two and eight weeks after inoculation. Following infusion of Dextran-SPION (0.1 µg and 1 µg Fe), the maximal distribution volume was observed at about 12-24 h after inoculation and two weeks later the Fe signals were undetectable for the lower dose. On the other hand, Au-SPION remained tightly localized in the closest vicinity of the infusion site as revealed by unchanged MRI signal intensities and strong histochemical staining of Fe2 + and Fe3 + ions in the corresponding brain slices. Immunohistochemical staining of astrocytic and microglial reactions revealed that there were no marked differences in GFAP, VIM or OX-42 labeling observed between the nanoparticle types, however the astrocytic reaction was more pronounced in rats receiving nanoparticles compared to the control (aCSF-infused) rats. In conclusion, the present data demonstrate that the viral-sized Dextran-SPION were able to diffuse freely through the interstitial space of the brain being progressively cleared out from the infusion site within two weeks. Thus, Dextran-SPION could be beneficially used in MRI-guided diagnostic applications such as in experimental oncology or as labels and carriers for targeted drug delivery, whereas Au-SPION could be used for labeling and tracking the transplanted stem cells in experimental MRI.

PET/NIRF/MRI triple functional iron oxide nanoparticles.

PubMed

Xie, Jin; Chen, Kai; Huang, Jing; Lee, Seulki; Wang, Jinhua; Gao, Jinhao; Li, Xingguo; Chen, Xiaoyuan

2010-04-01

Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the buildup of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with (64)Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area. Published by Elsevier Ltd.

Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors

PubMed Central

Dumont, Matthieu F; Yadavilli, Sridevi; Sze, Raymond W; Nazarian, Javad; Fernandes, Rohan

2014-01-01

Pediatric brain tumors (PBTs) are a leading cause of death in children. For an improved prognosis in patients with PBTs, there is a critical need to develop molecularly-specific imaging agents to monitor disease progression and response to treatment. In this paper, we describe manganese-containing Prussian blue nanoparticles as agents for molecular magnetic resonance imaging (MRI) and fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a core lattice structure that incorporates and retains paramagnetic Mn2+ ions, and generates MRI contrast (both negative and positive). The biofunctionalized shell is comprised of fluorescent avidin, which serves the dual purpose of enabling fluorescence imaging and functioning as a platform for the attachment of biotinylated ligands that target PBTs. The surfaces of our nanoparticles are modified with biotinylated antibodies targeting neuron-glial antigen 2 or biotinylated transferrin. Both neuron-glial antigen 2 and the transferrin receptor are protein markers overexpressed in PBTs. We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles. Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro. Finally, we demonstrate the potential of these nanoparticles as PBT imaging agents by measuring their organ and brain biodistribution in an orthotopic mouse model of PBTs using ex vivo fluorescence imaging. PMID:24920896

Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T₂ Contrast Agents for MRI.

PubMed

Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

2016-07-27

There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T₂ relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r₂, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.

A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

NASA Astrophysics Data System (ADS)

Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

2016-11-01

Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.

Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Petryk, Alicia A.; Tate, Jennifer A.; Savellano, Mark S.; Strawbridge, Rendall R.; Giustini, Andrew J.; Stan, Radu V.; Gimi, Barjor; Garwood, Michael

2013-02-01

The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3-10 fold range. Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an MRI technique which provides a

Polymer film-nanoparticle composites as new multimodality, non-migrating breast biopsy markers.

PubMed

Kaplan, Jonah A; Grinstaff, Mark W; Bloch, B Nicolas

2016-03-01

To develop a breast biopsy marker that resists fast and slow migration and has permanent visibility under commonly used imaging modalities. A polymer-nanoparticle composite film was prepared by embedding superparamagnetic iron oxide nanoparticles and a superelastic Nitinol wire within a flexible polyethylene matrix. MRI, mammography, and ultrasound were used to visualize the marker in agar, ex vivo chicken breast, bovine liver, brisket, and biopsy training phantoms. Fast migration caused by the "accordion effect" was quantified after simulated stereotactic, vacuum-assisted core biopsy/marker placement, and centrifugation was used to simulate accelerated long-term (i.e., slow) migration in ex vivo bovine tissue phantoms. Clear marker visualization under MRI, mammography, and ultrasound was observed. After deployment, the marker partially unfolds to give a geometrically constrained structure preventing fast and slow migration. The marker can be deployed through an 11G introducer without fast migration occurring, and shows substantially less slow migration than conventional markers. The polymer-nanoparticle composite biopsy marker is clearly visible on all clinical imaging modalities and does not show substantial migration, which ensures multimodal assessment of the correct spatial information of the biopsy site, allowing for more accurate diagnosis and treatment planning and improved breast cancer patient care. Polymer-nanoparticle composite biopsy markers are visualized using ultrasound, MRI, and mammography. Embedded iron oxide nanoparticles provide tuneable contrast for MRI visualization. Permanent ultrasound visibility is achieved with a non-biodegradable polymer having a distinct ultrasound signal. Flexible polymer-based biopsy markers undergo shape change upon deployment to minimize migration. Non-migrating multimodal markers will help improve accuracy of pre/post-treatment planning studies.

MRI based on iron oxide nanoparticles contrast agents: effect of oxidation state and architecture

NASA Astrophysics Data System (ADS)

Javed, Yasir; Akhtar, Kanwal; Anwar, Hafeez; Jamil, Yasir

2017-11-01

Iron oxide nanoparticles (IONPs) extensively employed beyond regenerative medicines to imaging disciplines because of their great constituents for magneto-responsive nano-systems. The unique superparamagnetic behavior makes IONPs very suitable for hyperthermia and imaging applications. From the last decade, versatile functionalization with surface capabilities, efficient contrast properties and biocompatibilities make IONPs an essential imaging contrast agent for magnetic resonance imaging (MRI). IONPs have shown signals for both longitudinal relaxation and transverse relaxation; therefore, negative contrast as well as dual contrast can be used for imaging in MRI. In the current review, we have focused on different oxidation state of iron oxides, i.e., magnetite, maghemite and hematite for their T1 and T2 contrast enhancement properties. We have also discussed different factors (synthesis protocols, biocompatibility, toxicity, architecture, etc.) that can affect the contrast properties of the IONPs. [Figure not available: see fulltext.

Brain Tumor Diagnostics and Therapeutics with Superparamagnetic Ferrite Nanoparticles.

PubMed

Hyder, Fahmeed; Manjura Hoque, S

2017-01-01

Ferrite nanoparticles (F-NPs) can transform both cancer diagnostics and therapeutics. Superparamagnetic F-NPs exhibit high magnetic moment and susceptibility such that in presence of a static magnetic field transverse relaxation rate of water protons for MRI contrast is augmented to locate F-NPs (i.e., diagnostics) and exposed to an alternating magnetic field local temperature is increased to induce tissue necrosis (i.e., thermotherapy). F-NPs are modified by chemical synthesis of mixed spinel ferrites as well as their size, shape, and coating. Purposely designed drug-containing nanoparticles (D-NPs) can slowly deliver drugs (i.e., chemotherapy). Convection-enhanced delivery (CED) of D-NPs with MRI guidance improves glioblastoma multiforme (GBM) treatment. MRI monitors the location of chemotherapy when D-NPs and F-NPs are coadministered with CED. However superparamagnetic field gradients produced by F-NPs complicate MRI readouts (spatial distortions) and MRS (extensive line broadening). Since extracellular pH (pH e ) is a cancer hallmark, pH e imaging is needed to screen cancer treatments. Biosensor imaging of redundant deviation in shifts (BIRDS) extrapolates pH e from paramagnetically shifted signals and the pH e accuracy remains unaffected by F-NPs. Hence effect of both chemotherapy and thermotherapy can be monitored (by BIRDS), whereas location of F-NPs is revealed (by MRI). Smarter tethering of nanoparticles and agents will impact GBM theranostics.

Durability improvements of two-dimensional metal nanoparticle sheets by molecular cross-linked structures between nanoparticles

NASA Astrophysics Data System (ADS)

Saito, Noboru; Ryuzaki, Sou; Wang, Pangpang; Park, Susie; Sakai, Nobuyuki; Tatsuma, Tetsu; Okamoto, Koichi; Tamada, Kaoru

2018-03-01

The durability of two-dimensional metal nanoparticle sheets is a crucial factor for realizing next-generation optoelectronic devices based on plasmonics such as organic light-emitting diodes. Here, we report improvements in the durability of Ag nanoparticle sheets by forming alkanedithiol (DT16) cross-linked structures between the nanoparticles. The cross-linked structures in a sheet were fabricated by the self-assembly of DT16-capped Ag nanoparticles with 10% coverage (AgDT16). The durabilities for thermal, organic solvent, and oxidation reactions of AgDT16 sheets were found to be improved owing to the cross-linked structures by comparing Ag nanoparticle sheets without the cross-linked structures. The absorbance spectra revealed that the Ag nanoparticle sheets without the structure are markedly damaged by each durability test, whereas the AgDT16 sheets remain. The molecular cross-linked structures between nanoparticles in two-dimansional metal nanoparticle sheets were found to have the potential to play a key role in the realization of plasmonic optoelectronic devices including metal nanoparticles.

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin

PubMed Central

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-01-01

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein–protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 μM Ca2+, suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 μM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens. PMID:17003117

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin.

PubMed

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-10-03

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein-protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 microM Ca(2+), suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 microM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens.

GADOLINIUM(Gd)-BASED and Ion Oxide Nanoparticle Contrast Agents for Pre-Clinical and Clinical Magnetic Resonance Imaging (mri) Research

NASA Astrophysics Data System (ADS)

Ng, Thian C.

2012-06-01

It is known that one strength of MRI is its excellent soft tissue discrimination. It naturally provides sufficient contrast between the structural differences of normal and pathological tissues, their spatial extent and progression. However, to further extend its applications and enhance even more contrast for clinical studies, various Gadolinium (Gd)-based contrast agents have been developed for different organs (brain strokes, cancer, cardio-MRI, etc). These Gd-based contrast agents are paramagnetic compounds that have strong T1-effect for enhancing the contrast between tissue types. Gd-contrast can also enhance magnetic resonance angiography (CE-MRA) for studying stenosis and for measuring perfusion, vascular susceptibility, interstitial space, etc. Another class of contrast agents makes use of ferrite iron oxide nanoparticles (including Superparamagnetic Ion Oxide (SPIO) and Ultrasmall Superparamagnetic Iron Oxide (USPIO)). These nanoparticles have superior magnetic susceptibility effect and produce a drop in signal, namely in T2*-weighted images, useful for the determination of lymph nodes metastases, angiogenesis and arteriosclerosis plaques.

Tunable and noncytotoxic PET/SPECT-MRI multimodality imaging probes using colloidally stable ligand-free superparamagnetic iron oxide nanoparticles

PubMed Central

Pham, TH Nguyen; Lengkeek, Nigel A; Greguric, Ivan; Kim, Byung J; Pellegrini, Paul A; Bickley, Stephanie A; Tanudji, Marcel R; Jones, Stephen K; Hawkett, Brian S; Pham, Binh TT

2017-01-01

Physiologically stable multimodality imaging probes for positron emission tomography/single-photon emission computed tomography (PET/SPECT)-magnetic resonance imaging (MRI) were synthesized using the superparamagnetic maghemite iron oxide (γ-Fe2O3) nanoparticles (SPIONs). The SPIONs were sterically stabilized with a finely tuned mixture of diblock copolymers with either methoxypolyethylene glycol (MPEG) or primary amine NH2 end groups. The radioisotope for PET or SPECT imaging was incorporated with the SPIONs at high temperature. 57Co2+ ions with a long half-life of 270.9 days were used as a model for the radiotracer to study the kinetics of radiolabeling, characterization, and the stability of the radiolabeled SPIONs. Radioactive 67Ga3+ and Cu2+-labeled SPIONs were also produced successfully using the optimized conditions from the 57Co2+-labeling process. No free radioisotopes were detected in the aqueous phase for the radiolabeled SPIONs 1 week after dispersion in phosphate-buffered saline (PBS). All labeled SPIONs were not only well dispersed and stable under physiological conditions but also noncytotoxic in vitro. The ability to design and produce physiologically stable radiolabeled magnetic nanoparticles with a finely controlled number of functionalizable end groups on the SPIONs enables the generation of a desirable and biologically compatible multimodality PET/SPECT-MRI agent on a single T2 contrast MRI probe. PMID:28184160

Intracellular bimodal nanoparticles based on quantum dots for high-field MRI at 21.1 T.

PubMed

Rosenberg, Jens T; Kogot, Joshua M; Lovingood, Derek D; Strouse, Geoffrey F; Grant, Samuel C

2010-09-01

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high-field MR applications-including biomedical imaging at 21.1 T, the highest magnetic field available for MRI-these nanoparticles capitalize on the improved performance of chelated Dy(3+) with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell-penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self-transfecting high-field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. 2010 Wiley-Liss, Inc.

Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.

PubMed

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Kumagai, Michiaki; Nomoto, Takahiro; Aoki, Ichio; Terada, Yasuko; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

2014-01-28

Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Nanoparticle-Enhanced MRI to Evaluate Radiation Delivery to the Regional Lymphatics for Patients With Breast Cancer

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

MacDonald, Shannon M., E-mail: smacdonald@partners.or; Harisinghani, Mukesh G.; Katkar, Amol

2010-07-15

Purpose: At present, radiation (RT) fields are based largely, and often solely, on bony anatomy. Recent efforts have been taken to better define lymphatic regions for RT planning. Lymphotrophic nanoparticle-enhanced MRI (LN-MRI) allows for accurate identification of malignant and benign lymph nodes. We sought to evaluate RT delivery to lymphatics for breast cancer using LN-MRI. Methods and Materials: Twenty-three patients with breast cancer underwent LN-MRI. MRIs were anatomically registered to a reference CT; benign and malignant lymph nodes were contoured. Standard RT fields were planned and dose calculated to prescribe 45-50 Gy. Lymphatic regions were contoured on CT. Coverage ofmore » LN-MRI lymph nodes by RT fields and contoured lymphatics were assessed. Results: Eighty-one percent of all lymph nodes defined by LN-MRI were covered by the 45-Gy isodose line; 82% of malignant and 79% of benign. The 50-Gy isodose line only encompassed 60% of LN-MRI defined lymph nodes-64% of malignant and 59% of benign. For nodal volumes contoured in the absence of a margin, 86% of actual lymph nodes were within contoured volumes. When a 5-mm expansion was added, 99% were included. Conclusions: LN-MRI is a useful tool to delineate the location of breast regional lymphatics. These results suggest less than desired coverage of lymph nodes using standard RT fields and that a margin may be advisable when defining nodal volumes by CT. The use of IMRT and RT in lieu of surgery makes accurate definition of the location of breast regional lymphatics of paramount importance.« less

Protein corona affects the relaxivity and MRI contrast efficiency of magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Amiri, Houshang; Bordonali, Lorenzo; Lascialfari, Alessandro; Wan, Sha; Monopoli, Marco P.; Lynch, Iseult; Laurent, Sophie; Mahmoudi, Morteza

2013-08-01

Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood. Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. 1H relaxometry was used to obtain the longitudinal, r1, and transverse, r2, relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at ν = 8.5 MHz were performed using a low-field MRI scanner. The MRI

Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging.

PubMed

Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Huebner, Frank; Zeuzem, Stefan; Korf, Hans W; Vogl, Thomas J; Rittmeyer, Claudia; Terfort, Andreas; Piiper, Albrecht; Gelperina, Svetlana; Kreuter, Jörg

2014-05-01

Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235±19nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable in vivo and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma. Copyright © 2013 Elsevier B.V. All rights reserved.

Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

NASA Astrophysics Data System (ADS)

Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

2005-05-01

A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

Gelatin-encapsulated iron oxide nanoparticles for platinum (IV) prodrug delivery, enzyme-stimulated release and MRI.

PubMed

Cheng, Ziyong; Dai, Yunlu; Kang, Xiaojiao; Li, Chunxia; Huang, Shanshan; Lian, Hongzhou; Hou, Zhiyao; Ma, Pingan; Lin, Jun

2014-08-01

A facile method for transferring hydrophobic iron oxide nanoparticles (IONPs) from chloroform to aqueous solution via encapsulation of FITC-modified gelatin based on the hydrophobic-hydrophobic interaction is described in this report. Due to the existence of large amount of active groups such as amine groups in gelatin, the fluorescent labeling molecules of fluorescein isothiocyanate (FITC) and platinum (IV) prodrug functionalized with carboxylic groups can be conveniently conjugated on the IONPs. The nanoparticles carrying Pt(IV) prodrug exhibit good anticancer activities when the Pt(IV) complexes are reduced to Pt(II) in the intracellular environment, while the pure Pt(IV) prodrug only presents lower cytotoxicity on cancer cells. Meanwhile, fluorescence of FITC on the surface of nanoparticles was completely quenched due to the possible Förster Resonance Energy Transfer (FRET) mechanism and showed a fluorescence recovery after gelatin release and detachment from IONPs. Therefore FITC as a fluorescence probe can be used for identification, tracking and monitoring the drug release. In addition, adding pancreatic enzyme can effectively promote the gelatin release from IONPs owing to the degradation of gelatin. Noticeable darkening in magnetic resonance image (MRI) was observed at the tumor site after in situ injection of nanoparticles, indicating the IONPs-enhanced T2-weighted imaging. Our results suggest that the gelatin encapsulated Fe3O4 nanoparticles have potential applications in multi-functional drug delivery system for disease therapy, MR imaging and fluorescence sensor. Copyright © 2014 Elsevier Ltd. All rights reserved.

In situ preparation of high relaxivity iron oxide nanoparticles by coating with chitosan: A potential MRI contrast agent useful for cell tracking

NASA Astrophysics Data System (ADS)

Tsai, Zei-Tsan; Wang, Jen-Fei; Kuo, Hsiao-Yun; Shen, Chia-Rui; Wang, Jiun-Jie; Yen, Tzu-Chen

2010-01-01

Iron oxide nanocrystals are of considerable interest in nanoscience and nanotechnology because of their nanoscale dimensions, nontoxic nature, and superior magnetic properties. Colloidal solutions of magnetic nanoparticles (ferrofluids) with a high magnetite content are highly desirable for most molecular imaging applications. In this paper, we present a method for in situ coating of superparamagnetic iron oxide (SPIO) with chitosan in order to increase the content of magnetite. Iron chloride salts (Fe 3+ and Fe 2+) were directly coprecipitated inside a porous matrix of chitosan by Co-60 γ-ray irradiation in an aqueous solution of acetic acid. Following sonication, iron oxide nanoparticles were formed inside the chitosan matrix at a pH value of 9.5 and a temperature of 50 °C. The [Fe 3+]:[Fe 2+]:[NH 4OH] molar ratio was 1.6:1:15.8. The final ferrofluid was formed with a pH adjustment to approximately 2.0/3.0, alongside with the addition of mannitol and lactic acid. We subsequently characterized the particle size, the zeta potential, the iron concentration, the magnetic contrast, and the cellular uptake of our ferrofluid. Results showed a z-average diameter of 87.2 nm, a polydispersity index (PDI) of 0.251, a zeta potential of 47.9 mV, and an iron concentration of 10.4 mg Fe/mL. The MRI parameters included an R1 value of 22.0 mM -1 s -1, an R2 value of 202.6 mM -1 s -1, and a R2/R1 ratio of 9.2. An uptake of the ferrofluid by mouse macrophages was observed. Altogether, our data show that Co-60 γ-ray radiation on solid chitosan may improve chitosan coating of iron oxide nanoparticles and tackle its aqueous solubility at pH 7. Additionally, our methodology allowed to obtain a ferrofluid with a higher content of magnetite and a fairly unimodal distribution of monodisperse clusters. Finally, MRI and cell experiments demonstrated the potential usefulness of this product as a potential MRI contrast agent that might be used for cell tracking.

Study of the intra-arterial distribution of Fe₃O₄ nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry.

PubMed

Echevarria-Uraga, José J; García-Alonso, Ignacio; Plazaola, Fernando; Insausti, Maite; Etxebarria, Néstor; Saiz-López, Alberto; Fernández-Ruanova, Begoña

2012-01-01

To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe₃O₄ lipophilic nanoparticles. WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe₃O₄ nanoparticles (2.6 mg) in Lipiodol® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland-Altman plots were produced; P values <0.05 were considered significant. In the CG rats (n = 23), the mean [Fe] values estimated by MRI and ICP-MS were 13.2 μmol·g⁻¹ and 5.9 μmol·g⁻¹, respectively, in the tumors, and 19.0 μmol ·g⁻¹ and 11.7 μmol·g⁻¹, respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 μmol·g⁻¹ and 9.4 μmol · g⁻¹, respectively, in the tumors, and 115.3 μmol·g⁻¹ and 11.6 μmol·g⁻¹, respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P < 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were observed, especially

CMC-coated Fe3O4 nanoparticles as new MRI probes for hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Sitthichai, Sudarat; Pilapong, Chalermchai; Thongtem, Titipun; Thongtem, Somchai

2015-11-01

Pure Fe3O4 nanoparticles and Fe3O4 magnetic nanoparticles (MNPs) coated with carboxymethyl cellulose (CMC) were successfully prepared by co-precipitating of FeCl2·4H2O and FeCl3·6H2O in the solutions containing ammonia at 80 °C for 3 h. Phase, morphology, particle-sized distribution, surface chemistry, and weight loss were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) including high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED), thermogravimetric analysis (TGA), and Fourier transform infrared (FTIR) spectroscopy. In this research, CMC-coated Fe3O4 MNPs consisting of Fe2+ and Fe3+ ions with 543.3-mM-1 s-1 high relaxivity were detected and were able to be used for magnetic resonance imaging (MRI) application with very good contrast for targeting hepatocellular carcinoma (HCC) without any further vectorization.

Superparamagnetic nanoparticles for cancer diagnostics and therapeutics

NASA Astrophysics Data System (ADS)

Kohler, Nathan

2005-11-01

This dissertation describes the development of a magnetic nanoparticle conjugate that can potentially serve as both a contrast enhancement agent in magnetic resonance imaging (MRI) and as a drug carrier in controlled drug release, targeted for cancer diagnostics and therapeutics. In this work, we developed a unique method to synthesize well-dispersed 10-nm superparamagnetic iron oxide nanoparticles (SPION) without using chemical surfactants. This approach is especially advantageous for subsequent surface modification of nanoparticles with functional coatings. To target the SPION for cancer cells in vivo to facilitate MRI contrast enhancement of tumors, we immobilized folic acid on the particle surface. Folic acid is a low molecular weight growth factor over-expressed on many forms of cancer. The covalent immobilization of folic acid to the nanoparticle surface was characterized with FTIR and the intracellular uptake of the folic acid nanoparticles was visualized with scanning confocal microscopy. To use SPION for controlled drug release, we immobilized methotrexate (MTX), a chemotherapeutic drug, to the nanoparticle surface. MTX-modified nanoparticles have several combined advantages including real-time monitoring of drug delivery using MRI, higher intracellular concentrations of methotrexate that increase cellular cytotoxicity, and reduced non-specific uptake by healthy cells within the body. We successfully conducted drug release experiments demonstrating that MTX was released under low pH conditions that mimic the intracellular conditions in the lysozome. To assess cellular cytotoxicity, we tested MTX-nanoparticle conjugates in human breast cancer cells (MCF-7), human cervical cancer cells (HeLa), and glioma cells (9L), and showed that the drug efficacy of MTX-nanoparticle conjugates was similar to that of free MTX. To improve nanoparticle circulation time and intracellular uptake, we developed a novel bifunctional poly(ethylene glycol) (PEG) SAM capable of

Cell viability and MRI performance of highly efficient polyol-coated magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Arteaga-Cardona, Fernando; Gutiérrez-García, Eric; Hidalgo-Tobón, Silvia; López-Vasquez, Ciro; Brito-Barrera, Yazmín A.; Flores-Tochihuitl, Julia; Angulo-Molina, Aracely; Reyes-Leyva, Julio R.; González-Rodríguez, Roberto; Coffer, Jeffery L.; Pal, Umapada; Diaz-Conti, Mario Pérez-Peña; Platas-Neri, Diana; Dies-Suarez, Pilar; Fonseca, Rebeca Sosa; Arias-Carrión, Oscar; Méndez-Rojas, Miguel A.

2016-11-01

This work aimed at determining conditions that would allow us to control the size of the NPs and create a system with characteristics apt for biomedical applications. We describe a comprehensive study on the synthesis and physical characterization of two highly sensitive sets of triethylene glycol (TREG) and polyethylene glycol (PEG)-coated superparamagnetic iron oxide nanoparticles (SPIONs) to be evaluated for use as magnetic resonance (MR) contrast agents. The ferrofluids demonstrated excellent colloidal stability in deionized water at pH 7.0 as indicated by dynamic light scattering (DLS) data. The magnetic relaxivities, r 2, were measured on a 1.5 T clinical MRI instrument. Values in the range from 205 to 257 mM-1 s-1 were obtained, varying proportionally to the SPIONs' sizes and coating nature. Further in vitro cell viability tests and in vivo biodistribution analyses of the intravenously administered nanoparticles showed that the prepared systems have good biocompatibility and migrate to several organs, mainly the meninges, spleen, and liver. Based on these results, our findings demonstrated the potential utility of these nanosystems as clinical contrast agents for MR imaging.

Improving fMRI reliability in presurgical mapping for brain tumours.

PubMed

Stevens, M Tynan R; Clarke, David B; Stroink, Gerhard; Beyea, Steven D; D'Arcy, Ryan Cn

2016-03-01

Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps. Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel. The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively). We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System.

PubMed

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Masarudin, Mas Jaffri; Ahmad Saad, Fathinul Fikri

2017-08-31

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO₃)₃ as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System

PubMed Central

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Ahmad Saad, Fathinul Fikri

2017-01-01

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO3)3 as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment. PMID:28858229

Surface impact on nanoparticle-based magnetic resonance imaging contrast agents

PubMed Central

Zhang, Weizhong; Liu, Lin; Chen, Hongmin; Hu, Kai; Delahunty, Ian; Gao, Shi; Xie, Jin

2018-01-01

Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. To improve imaging quality, MRI contrast agents, which can modulate local T1 and T2 relaxation times, are often injected prior to or during MRI scans. However, clinically used contrast agents, including Gd3+-based chelates and iron oxide nanoparticles (IONPs), afford mediocre contrast abilities. To address this issue, there has been extensive research on developing alternative MRI contrast agents with superior r1 and r2 relaxivities. These efforts are facilitated by the fast progress in nanotechnology, which allows for preparation of magnetic nanoparticles (NPs) with varied size, shape, crystallinity, and composition. Studies suggest that surface coatings can also largely affect T1 and T2 relaxations and can be tailored in favor of a high r1 or r2. However, the surface impact of NPs has been less emphasized. Herein, we review recent progress on developing NP-based T1 and T2 contrast agents, with a focus on the surface impact. PMID:29721097

Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

PubMed

Cowger, Taku A; Tang, Wei; Zhen, Zipeng; Hu, Kai; Rink, David E; Todd, Trever J; Wang, Geoffrey D; Zhang, Weizhong; Chen, Hongmin; Xie, Jin

2015-01-01

Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

Intrinsically radiolabelled [(59)Fe]-SPIONs for dual MRI/radionuclide detection.

PubMed

Hoffman, David; Sun, Minghao; Yang, Likun; McDonagh, Philip R; Corwin, Frank; Sundaresan, Gobalakrishnan; Wang, Li; Vijayaragavan, Vimalan; Thadigiri, Celina; Lamichhane, Narottam; Zweit, Jamal

2014-01-01

Towards the development of iron oxide nanoparticles with intrinsically incorporated radionuclides for dual Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) and more recently of Single Photon Emission Computed Tomography/Magnetic Resonance Imaging (SPECT/MRI), we have developed intrinsically radiolabeled [(59)Fe]-superparamagnetic iron oxide nanoparticles ([(59)Fe]-SPIONs) as a proof of concept for an intrinsic dual probe strategy. (59)Fe was incorporated into Fe3O4 nanoparticle crystal lattice with 92±3% efficiency in thermal decomposition synthesis. Multidentate poly(acrylic acid)-dopamine-poly(ethylene-glycol-2000) (PAA-DOP-PEG) ligands were designed and synthesized based on facile EDC chemistry and utilized to functionalize the [(59)Fe]-SPIONs. The transverse relaxivity of [(59)Fe]-SPIONs (97±3 s(-1)mM(-1)) was characterized and found to be similar to non-radioactive SPIONs (72±10 s(-1)mM(-1)), indicating that (59)Fe incorporation does not alter the SPIONs' MRI contrast properties. [(59)Fe]-SPIONs were used to evaluate the nanoparticle biodistribution by ex vivo gamma counting and MRI. Nude mice (n=15) were injected with [(59)Fe]-SPIONs and imaged at various time points with 7T small animal MRI scanner. Ex vivo biodistribution was evaluated by tissue-based gamma counting. MRI signal contrast qualitatively correlates with the %ID/g of [(59)Fe]-SPIONs, with high contrast in liver (45±6%), medium contrast in kidneys (21±5%), and low contrast in brain (4±6%) at 24 hours. This work demonstrates the synthesis and in vivo application of intrinsically radiolabeled [(59)Fe]-SPIONs for bimodal detection and provides a proof of concept for incorporation of both gamma- and positron-emitting inorganic radionuclides into the core of metal based MRI contrast agent nanoparticles.

Implementation of time-efficient adaptive sampling function design for improved undersampled MRI reconstruction

NASA Astrophysics Data System (ADS)

Choi, Jinhyeok; Kim, Hyeonjin

2016-12-01

To improve the efficacy of undersampled MRI, a method of designing adaptive sampling functions is proposed that is simple to implement on an MR scanner and yet effectively improves the performance of the sampling functions. An approximation of the energy distribution of an image (E-map) is estimated from highly undersampled k-space data acquired in a prescan and efficiently recycled in the main scan. An adaptive probability density function (PDF) is generated by combining the E-map with a modeled PDF. A set of candidate sampling functions are then prepared from the adaptive PDF, among which the one with maximum energy is selected as the final sampling function. To validate its computational efficiency, the proposed method was implemented on an MR scanner, and its robust performance in Fourier-transform (FT) MRI and compressed sensing (CS) MRI was tested by simulations and in a cherry tomato. The proposed method consistently outperforms the conventional modeled PDF approach for undersampling ratios of 0.2 or higher in both FT-MRI and CS-MRI. To fully benefit from undersampled MRI, it is preferable that the design of adaptive sampling functions be performed online immediately before the main scan. In this way, the proposed method may further improve the efficacy of the undersampled MRI.

Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

NASA Astrophysics Data System (ADS)

Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

2016-02-01

Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g-1). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM-1 s-1 and 185.58 mM-1 s-1 respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high

Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods

NASA Astrophysics Data System (ADS)

Raeesi, Vahid; Chan, Warren C. W.

2016-06-01

Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside tumor tissue can improve the transport of large nanoparticles through collagen (I) matrix. The ability to increase nanoparticles diffusion inside tumor stroma allows their targeting or other functionalities to take effect, thereby significantly improving cancer therapeutic or diagnostic outcome.Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside

Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry

PubMed Central

Echevarria-Uraga, José J; García-Alonso, Ignacio; Plazaola, Fernando; Insausti, Maite; Etxebarria, Néstor; Saiz-López, Alberto; Fernández-Ruanova, Begoña

2012-01-01

Purpose To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe3O4 lipophilic nanoparticles. Materials and methods WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe3O4 nanoparticles (2.6 mg) in Lipiodol® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland–Altman plots were produced; P values <0.05 were considered significant. Results In the CG rats (n = 23), the mean [Fe] values estimated by MRI and ICP-MS were 13.2 μmol·g−1 and 5.9 μmol·g−1, respectively, in the tumors, and 19.0μmol ·g−1 and 11.7 μmol·g−1, respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 μmol·g−1 and 9.4 μmol · g−1, respectively, in the tumors, and 115.3 μmol·g−1 and 11.6 μmol·g−1, respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P < 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were

Multifunctional fluorescent and magnetic nanoparticles for biomedical applications

NASA Astrophysics Data System (ADS)

Selvan, Subramanian T.

2012-03-01

Hybrid multifunctional nanoparticles (NPs) are emerging as useful probes for magnetic based targeting, delivery, cell separation, magnetic resonance imaging (MRI), and fluorescence-based bio-labeling applications. Assessing from the literature, the development of multifunctional NPs for multimodality imaging is still in its infancy state. This report focuses on our recent work on quantum dots (QDs), magnetic NPs (MNPs) and bi-functional NPs (composed of either QDs or rare-earth NPs, and magnetic NPs - iron oxide or gadolinium oxide) for multimodality imaging based biomedical applications. The combination of MRI and fluorescence would ally each other in improving the sensitivity and resolution, resulting in improved and early diagnosis of the disease. The challenges in this area are discussed.

Magnetic properties, water proton relaxivities, and in-vivo MR images of paramagnetic nanoparticles

NASA Astrophysics Data System (ADS)

Lee, Gang Ho; Chang, Yongmin

2015-07-01

In this mini review, magnetic resonance imaging (MRI) contrast agents based on lanthanideoxide (Ln2O3) nanoparticles are described. Ln2O3 (Ln = Gd, Dy, Ho, and Er) nanoparticles are paramagnetic, but show appreciable magnetic moments at room temperature and even at ultrasmall particle diameters. Among Ln2O3 nanoparticles, Gd2O3 nanoparticles show larger longitudinal water proton relaxivity (r1) values than Gd-chelates because of the large amount of Gd in the nanoparticle, and the other Ln2O3 nanoparticles (Ln = Dy, Ho, and Er) show appreciable transverse water proton relaxivity (r2) values. Therefore, Gd2O3 nanoparticles are potential T1 MRI contrast agents while the other Ln2O3 nanoparticles are potential T2 MRI contrast agents at high MR fields.

Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies

NASA Astrophysics Data System (ADS)

Guillet-Nicolas, Rémy; Laprise-Pelletier, Myriam; Nair, Mahesh M.; Chevallier, Pascale; Lagueux, Jean; Gossuin, Yves; Laurent, Sophie; Kleitz, Freddy; Fortin, Marc-André

2013-11-01

Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn2+ is already implemented as a ``positive'' cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(ii) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn2+ leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM-1 s-1 were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because

Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

NASA Astrophysics Data System (ADS)

Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

2015-07-01

Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

Gold nanoparticles to improve HIV drug delivery.

PubMed

Garrido, Carolina; Simpson, Carrie A; Dahl, Noelle P; Bresee, Jamee; Whitehead, Daniel C; Lindsey, Erick A; Harris, Tyler L; Smith, Candice A; Carter, Carly J; Feldheim, Daniel L; Melander, Christian; Margolis, David M

2015-01-01

Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART. Two to ten nanometer diameter inorganic gold crystals serve as a base scaffold to combine molecules with an array of properties in its surface. We show entry into different cell types, antiviral activity of an HIV integrase inhibitor conjugated in a gold nanoparticle and penetration into the brain in vivo without toxicity. Herein, gold nanoparticles prove to be a promising tool to use in HIV therapy.

Improving proton therapy by metal-containing nanoparticles: nanoscale insights

PubMed Central

Schlathölter, Thomas; Eustache, Pierre; Porcel, Erika; Salado, Daniela; Stefancikova, Lenka; Tillement, Olivier; Lux, Francois; Mowat, Pierre; Biegun, Aleksandra K; van Goethem, Marc-Jan; Remita, Hynd; Lacombe, Sandrine

2016-01-01

The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/μm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting. PMID:27143877

Synthesis and surface modification of magnetic nanoparticles for in vivo biomedical applications

NASA Astrophysics Data System (ADS)

Sun, Conroy Ghin Chee

Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform to serve as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to engineer the features and properties of MNPs allowing them to be tailored specifically for these biomedical applications. MNPs composed of metallic, oxide, and nanoalloy cores and a variety of protective coatings are being investigated for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed. The goal of this interdisciplinary research is to develop novel superparamagnetic nanoprobes for non-invasive cancer diagnosis and treatment. This strategy utilizes iron oxide nanoparticles coated with various biocompatible polymers, such as poly(ethylene glycol) (PEG) and chitosan, to serve as both a contrast agent for MRI and a carrier for drug delivery. In this project, we have conjugated various targeting agents, such as folic acid (FA) and chlorotoxin (CTX), to these iron oxide nanoparticles to improve their tumor specific accumulation. The folate receptor is known to be overexpressed on the surfaces of many human tumor cells, including ovarian, lung, breast, endometrial, renal, and colon cancers, while CTX binds with high affinity to gliomas, medulloblastomas, and other tumors of the neuroectodermal origin. To evaluate its effectiveness as a targeted drug carrier, methotrexate (MTX), a convention chemotherapeutic agent, was conjugated to iron oxide nanoparticles in combination with CTX. Specific tumor cell targeting of our nanoparticle system has been demonstrated through increased contrast

Radiolabeled cyclic arginine-glycine-aspartic (RGD)-conjugated iron oxide nanoparticles as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer

NASA Astrophysics Data System (ADS)

Deng, Shengming; Zhang, Wei; Zhang, Bin; Hong, Ruoyu; Chen, Qing; Dong, Jiajia; Chen, Yinyiin; Chen, Zhiqiang; Wu, Yiwei

2015-01-01

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) modified with a novel cyclic arginine-glycine-aspartate (RGD) peptide were made and radiolabeled as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer. The probe was tested both in vitro and in vivo to determine its receptor targeting efficacy and feasibility for SPECT and MRI. The radiochemical syntheses of 125I-cRGD-USPIO were accomplished with a radiochemical purity of 96.05 ± 0.33 %. High radiochemical stability was found in fresh human serum and in phosphate-buffered saline. The average hydrodynamic size of 125I-cRGD-USPIO determined by dynamic light scattering was 51.3 nm. Results of in vitro experiments verified the specificity of the radiolabeled nanoparticles to tumor cells. Preliminary biodistribution studies of 125I-radiolabeled cRGD-USPIO in Bcap37-bearing nude mice showed that it had long circulation half-life, high tumor uptake, and high initial blood retention with moderate liver uptake. In vivo tumor targeting and uptake of the radiolabeled nanoparticles in mice model were visualized by SPECT and MRI collected at different time points. Our results strongly indicated that the 125I-cRGD-USPIO could be used as a promising bifunctional radiotracer for early clinical tumor detection with high sensitivity and high spatial resolution by SPECT and MRI.

Clinically Approved Nanoparticle Imaging Agents

PubMed Central

Thakor, Avnesh S.; Jokerst, Jesse V.; Ghanouni, Pejman; Campbell, Jos L.; Mittra, Erik

2016-01-01

Nanoparticles are a new class of imaging agent used for both anatomic and molecular imaging. Nanoparticle-based imaging exploits the signal intensity, stability, and biodistribution behavior of submicron-diameter molecular imaging agents. This review focuses on nanoparticles used in human medical imaging, with an emphasis on radionuclide imaging and MRI. Newer nanoparticle platforms are also discussed in relation to theranostic and multimodal uses. PMID:27738007

Using Nanoparticles in Medicine for Liver Cancer Imaging.

PubMed

Moghadam, Farideh Farokhi

2017-07-01

One of the most important types of liver cancer is hepatocellular carcinoma (HCC). HCC is the fifth most common cancer, and its correct diagnosis is very important. For the quick diagnosis of HCC, the use of nanoparticles is helpful. The major applications of nanoparticles are in medicine for organ imaging. Two methods of liver imaging are X-ray computed tomography (CT) and magnetic resonance imaging (MRI). In this review, we attempt to summarize some of the contrast agents used in imaging such as superparamagnetic iron oxide nanoparticles (SPIONs) and iron oxide nanoparticles (IONPs), various types of enhanced MRI for the liver, and nanoparticles like gold (AuNPs), which is used to develop novel CT imaging agents.

Assessing Intrarenal Non-perfusion and Vascular Leakage in Acute Kidney Injury withzz 19F MRI and Perfluorocarbon Nanoparticles

PubMed Central

Hu, Lingzhi; Chen, Junjie; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Yanaba, Noriko; Caruthers, Shelton D.; Lanza, Gregory M.; Hammerman, Marc R.; Wickline, Samuel A.

2014-01-01

Purpose We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles (PFC NPs) and 19F MRI. Methods Because the detected 19F signal intensity directly reflects local blood volume, and the 19F R1 is linearly proportional to local blood oxygen content (pO2), 19F spin density weighted and T1 weighted images were utilized to generate quantitative functional mapping in both healthy and ischemia-reperfusion (acute kidney injury, AKI) injured mouse kidneys. 1H Blood-Oxygenation-Level-Dependant (BOLD) MRI was also employed as a supplementary approach to facilitate the compressive analysis of renal circulation and its pathological changes in AKI. Results Heterogeneous blood volume distribution and intrarenal oxygenation gradient were confirmed in healthy kidneys by 19F MRI. In a mouse model of AKI, 19F MRI, in conjunction with BOLR MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary (CM) junction region, we observed 25% lower 19F signal (p<0.05) and 70% longer 1H T2* (p<0.01) in injured kidneys compared to contralateral kidneys at 24 hours after initial ischemia-reperfusion injury. We also detected 71% higher 19F signal (p<0.01) and 40% lower 1H T2* (p<0.05) in the renal medulla region of injured kidneys compared to contralateral kidneys. Conclusion With demonstrated superior diagnostic capability, functional kidney 19F MRI using PFC NPs could serve as a new diagnostic measures for comprehensive evaluation of renal function and pathology. PMID:23929727

Gold nanoparticles to improve HIV drug delivery

PubMed Central

Garrido, Carolina; Simpson, Carrie A; Dahl, Noelle P; Bresee, Jamee; Whitehead, Daniel C; Lindsey, Erick A; Harris, Tyler L; Smith, Candice A; Carter, Carly J; Feldheim, Daniel L; Melander, Christian; Margolis, David M

2015-01-01

Background: Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART. Results & Conclusion: Two to ten nanometer diameter inorganic gold crystals serve as a base scaffold to combine molecules with an array of properties in its surface. We show entry into different cell types, antiviral activity of an HIV integrase inhibitor conjugated in a gold nanoparticle and penetration into the brain in vivo without toxicity. Herein, gold nanoparticles prove to be a promising tool to use in HIV therapy. PMID:26132521

MRI tracing non-invasive TiO2-based nanoparticles activated by ultrasound for multi-mechanism therapy of prostatic cancer

NASA Astrophysics Data System (ADS)

Yuan, Pu; Song, Dongkui

2018-03-01

To reduce the side effects of chemotherapy and achieve effective and safe therapy for prostate cancer, herein a simple but multi-functional TiO2:Gd@DOX/FA system activated by ultrasound was developed for the MRI-guided multi-mechanism therapy of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a nanocarrier with the pH-responsive release of DOX. The doping of Gd was not only able to endow the TiO2 with magnetic resonance imaging (MRI) ability, but also further improve the sonodynamic ability of the TiO2. The characterization of the as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high reactive oxygen species (ROS) production, T 1-MRI contrast performance and excellent biocompatibility. The cytotoxicity assay in vitro showed cell death up to 91.68% after 48 h incubation induced by the TiO2:Gd@DOX + ultrasound group. Meanwhile, in the in vivo synergistic therapy studies, the tumor sizes of all the nanomedicine groups were smaller than for the free DOX (V:V 0 = 4.2). More importantly, the body showed nearly no weight loss. This safety was also confirmed by the H&E staining, biodistribution experiment and serum biochemistry results. Altogether, TiO2:Gd@DOX/FA significantly reduced the side effects of DOX, augmented the levels of ROS and achieved effective and safe therapy, indicating its potential for the multi-mechanism therapy of prostate cancer. There is no conflict of interest in this study and no funding has been received for it. We received the approval of the Research Ethics Committee before conducting this study.

Positive MRI contrast enhancement in THP-1 cells with Gd2O3 nanoparticles.

PubMed

Klasson, Anna; Ahrén, Maria; Hellqvist, Eva; Söderlind, Fredrik; Rosén, Anders; Käll, Per-Olov; Uvdal, Kajsa; Engström, Maria

2008-01-01

There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s(-1) mm(-1) for cell culture medium. The r2 was 17.4 and 12.9 s(-1) mm(-1), respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (p(r1) = 0.36), but r2 was significantly different for the two different series (p(r2) = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells. Copyright 2008 John Wiley & Sons, Ltd.

High MRI performance fluorescent mesoporous silica-coated magnetic nanoparticles for tracking neural progenitor cells in an ischemic mouse model

NASA Astrophysics Data System (ADS)

Zhang, Lu; Wang, Yao; Tang, Yaohui; Jiao, Zheng; Xie, Chengying; Zhang, Haijiao; Gu, Ping; Wei, Xunbin; Yang, Guo-Yuan; Gu, Hongchen; Zhang, Chunfu

2013-05-01

Multifunctional probes with high MRI sensitivity and high efficiency for cell labeling are desirable for MR cell imaging. Herein, we have fabricated fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) for neural progenitor cell (C17.2) MR imaging. FmSiO4@SPIONs were discrete and uniform in size, and had a clear core-shell structure. The magnetic core size was about 10 nm and the fluorescent mesoporous silica coating layer was around 20 nm. Compared with fluorescent dense silica-coated SPIONs (fdSiO4@SPIONs) with a similar size, fmSiO4@SPIONs demonstrated higher MR sensitivity and cell labeling efficiency. When implanted into the right hemisphere of stroke mice, contralateral to the ischemic territory, a small amount of labeled cells were able to be tracked migrating to the lesion sites using a clinical MRI scanner (3 T). More impressively, even when administered intravenously, the labeled cells could also be monitored homing to the ischemic area. MRI observations were corroborated by histological studies of the brain tissues. Our study demonstrated that fmSiO4@SPIONs are highly effective for cell imaging and hold great promise for MRI cell tracking in future.Multifunctional probes with high MRI sensitivity and high efficiency for cell labeling are desirable for MR cell imaging. Herein, we have fabricated fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) for neural progenitor cell (C17.2) MR imaging. FmSiO4@SPIONs were discrete and uniform in size, and had a clear core-shell structure. The magnetic core size was about 10 nm and the fluorescent mesoporous silica coating layer was around 20 nm. Compared with fluorescent dense silica-coated SPIONs (fdSiO4@SPIONs) with a similar size, fmSiO4@SPIONs demonstrated higher MR sensitivity and cell labeling efficiency. When implanted into the right hemisphere of stroke mice, contralateral to the ischemic territory, a small amount of

Structured reporting of MRI of the shoulder - improvement of report quality?

PubMed

Gassenmaier, Sebastian; Armbruster, Marco; Haasters, Florian; Helfen, Tobias; Henzler, Thomas; Alibek, Sedat; Pförringer, Dominik; Sommer, Wieland H; Sommer, Nora N

2017-10-01

To evaluate the effect of structured reports (SRs) in comparison to non-structured narrative free text (NRs) shoulder MRI reports and potential effects of both types of reporting on completeness, readability, linguistic quality and referring surgeons' satisfaction. Thirty patients after trauma or with suspected degenerative changes of the shoulder were included in this study (2012-2015). All patients underwent shoulder MRI for further assessment and possible surgical planning. NRs were generated during clinical routine. Corresponding SRs were created using a dedicated template. All 60 reports were evaluated by two experienced orthopaedic shoulder surgeons using a questionnaire that included eight questions. Eighty per cent of the SRs were fully complete without any missing key features whereas only 45% of the NRs were fully complete (p < 0.001). The extraction of information was regarded to be easy in 92% of the SRs and 63% of the NRs. The overall quality of the SRs was rated better than that of the NRs (p < 0.001). Structured reporting of shoulder MRI improves the readability as well as the linguistic quality of radiological reports, and potentially leads to a higher satisfaction of referring physicians. • Structured MRI reports of the shoulder improve readability. • Structured reporting facilitates information extraction. • Referring physicians prefer structured reports to narrative free text reports. • Structured MRI reports of the shoulder can reduce radiologist re-consultations.

Monodisperse magnetite (Fe3O4) nanoparticles modified with water soluble polymers for the diagnosis of breast cancer by MRI method

NASA Astrophysics Data System (ADS)

Rezayan, Ali Hossein; Mousavi, Majid; Kheirjou, Somayyeh; Amoabediny, Ghasem; Ardestani, Mehdi Shafiee; Mohammadnejad, Javad

2016-12-01

In this study, magnetic nanoparticles (MNPs) were synthesized via co-precipitation method. To enhance the biocompatibility and colloidal stability of the synthesized nanoparticles, they were modified with carboxyl functionalized PEG via dopamine (DPA) linker. Both modified and unmodified Fe3O4 nanoparticles exhibited super paramagnetic behavior (particle size below 20 nm). The saturation magnetization (Ms) of PEGdiacid-modified Fe3O4 was 45 emu/g, which was less than the unmodified Fe3O4 nanoparticles (70 emu/g). This difference indicated that PEGdiacid polymer was immobilized on the surface of Fe3O4 nanoparticles successfully. To evaluate the efficiency of the resulting nanoparticles as contrast agents for magnetic resonance imaging (MRI), different concentration of MNPs and different value of echo time TE were investigated. The results showed that by increasing the concentration of the nanoparticles, transverse relaxation time (T2) decreased, which subsequently resulted in MR signal enhancement. T2-weighted MR images of the different concentration of MNPs in different value of echo time TE indicated that MR signal intensity increased with increase in TE value up to 66 and then remained constant. The cytotoxicity effect of the modified and unmodified nanoparticles was evaluated in three different concentrations (12, 60 and 312 mg l-1) on MDA-MB-231 cancer cells for 24 and 48 h. In both tested time (24 and 48 h) for all three samples, the modified nanoparticles had long life time than unmodified nanoparticles. Cellular uptake of modified MNPs was 80% and reduced to 9% by the unmodified MNPs.

Improving the Test-Retest Reliability of Resting State fMRI by Removing the Impact of Sleep.

PubMed

Wang, Jiahui; Han, Junwei; Nguyen, Vinh T; Guo, Lei; Guo, Christine C

2017-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) provides a powerful tool to examine large-scale neural networks in the human brain and their disturbances in neuropsychiatric disorders. Thanks to its low demand and high tolerance, resting state paradigms can be easily acquired from clinical population. However, due to the unconstrained nature, resting state paradigm is associated with excessive head movement and proneness to sleep. Consequently, the test-retest reliability of rs-fMRI measures is moderate at best, falling short of widespread use in the clinic. Here, we characterized the effect of sleep on the test-retest reliability of rs-fMRI. Using measures of heart rate variability (HRV) derived from simultaneous electrocardiogram (ECG) recording, we identified portions of fMRI data when subjects were more alert or sleepy, and examined their effects on the test-retest reliability of functional connectivity measures. When volumes of sleep were excluded, the reliability of rs-fMRI is significantly improved, and the improvement appears to be general across brain networks. The amount of improvement is robust with the removal of as much as 60% volumes of sleepiness. Therefore, test-retest reliability of rs-fMRI is affected by sleep and could be improved by excluding volumes of sleepiness as indexed by HRV. Our results suggest a novel and practical method to improve test-retest reliability of rs-fMRI measures.

Optimizing MRI Logistics: Focused Process Improvements Can Increase Throughput in an Academic Radiology Department.

PubMed

O'Brien, Jeremy J; Stormann, Jeremy; Roche, Kelli; Cabral-Goncalves, Ines; Monks, Annamarie; Hallett, Donna; Mortele, Koenraad J

2017-02-01

The purpose of this study was to describe and evaluate the effect of focused process improvements on protocol selection and scheduling in the MRI division of a busy academic medical center, as measured by examination and room times, magnet fill rate, and potential revenue increases and cost savings to the department. Focused process improvements, led by a multidisciplinary team at a large academic medical center, were directed at streamlining MRI protocols and optimizing matching protocol ordering to scheduling while maintaining or improving image quality. Data were collected before (June 2013) and after (March 2015) implementation of focused process improvements and divided by subspecialty on type of examination, allotted examination time, actual examination time, and MRI parameters. Direct and indirect costs were compiled and analyzed in consultation with the business department. Data were compared with evaluated effects on selected outcome and efficiency measures, as well as revenue and cost considerations. Statistical analysis was performed using a t test. During the month of June 2013, 2145 MRI examinations were performed at our center; 2702 were performed in March 2015. Neuroradiology examinations were the most common (59% in June 2013, 56% in March 2015), followed by body examinations (25% and 27%). All protocols and parameters were analyzed and streamlined for each examination, with slice thickness, TR, and echo train length among the most adjusted parameters. Mean time per examination decreased from 43.4 minutes to 36.7 minutes, and mean room time per patient decreased from 46.3 to 43.6 minutes (p = 0.009). Potential revenue from increased throughput may yield up to $3 million yearly (at $800 net revenue per scan) or produce cost savings if the facility can reduce staffed scanner hours or the number of scanners in its fleet. Actual revenue and expense impacts depend on the facility's fixed and variable cost structure, payer contracts, MRI fleet composition

Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer.

PubMed

Semkina, Alevtina S; Abakumov, Maxim A; Skorikov, Alexander S; Abakumova, Tatiana O; Melnikov, Pavel A; Grinenko, Nadejda F; Cherepanov, Sergey A; Vishnevskiy, Daniil A; Naumenko, Victor A; Ionova, Klavdiya P; Majouga, Alexander G; Chekhonin, Vladimir P

2018-05-03

In presented paper we have developed new system for cancer theranostics based on vascular endothelial growth factor (VEGF) targeted magnetic nanoparticles. Conjugation of anti-VEGF antibodies with bovine serum albumin coated PEGylated magnetic nanoparticles allows for improved binding with murine breast adenocarcinoma 4T1 cell line and facilitates doxorubicin delivery to tumor cells. It was shown that intravenous injection of doxorubicin loaded VEGF targeted nanoparticles increases median survival rate of mice bearing 4T1 tumors up to 50%. On the other hand magnetic resonance imaging (MRI) of 4T1 tumors 24 h after intravenous injection showed accumulation of nanoparticles in tumors, thus allowing simultaneous cancer therapy and diagnostics. Copyright © 2018. Published by Elsevier Inc.

Water-Soluble Spinel Ferrites by a Modified Polyol Process as Contrast Agents in MRI

NASA Astrophysics Data System (ADS)

Basina, Georgia; Tzitzios, Vasilis; Niarchos, Dimitris; Li, Wanfeng; Khurshid, Hafsa; Mao, Hui; Hadjipanayis, Costas; Hadjipanayis, George

2010-12-01

Magnetic nanoparticles have recently been very attractive for biomedical applications. In this study, we have synthesized ferrite nanoparticles for application as contrast agents in MRI experiments. Fe3O4 and MnFe2O4 spinel ferrites with a mean size of 11-12 nm, were prepared by a modified polyol route in commercially available polyethylene glycol with molecular weight 600 (PEG-600). The reaction takes place in the presence of water soluble and non-toxic tri-block copolymer known as Pluronic® F-127 (PEO100-PPO65-PEO100). The nanoparticles have saturation magnetization values of 52 and 68 emu/g for MnFe2O4 and Fe3O4, respectively. Both the Fe3O4, and MnFe2O4 nanoparticles make stable solutions in water known as ferrofluids. Preliminary data demonstrated the capability of these nanoparticles to induce imaging contrast in T2 weighted MRI experiments, making these materials suitable for biomedical applications such as medical MRI.

High MRI performance fluorescent mesoporous silica-coated magnetic nanoparticles for tracking neural progenitor cells in an ischemic mouse model.

PubMed

Zhang, Lu; Wang, Yao; Tang, Yaohui; Jiao, Zheng; Xie, Chengying; Zhang, Haijiao; Gu, Ping; Wei, Xunbin; Yang, Guo-Yuan; Gu, Hongchen; Zhang, Chunfu

2013-05-21

Multifunctional probes with high MRI sensitivity and high efficiency for cell labeling are desirable for MR cell imaging. Herein, we have fabricated fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) for neural progenitor cell (C17.2) MR imaging. FmSiO4@SPIONs were discrete and uniform in size, and had a clear core-shell structure. The magnetic core size was about 10 nm and the fluorescent mesoporous silica coating layer was around 20 nm. Compared with fluorescent dense silica-coated SPIONs (fdSiO4@SPIONs) with a similar size, fmSiO4@SPIONs demonstrated higher MR sensitivity and cell labeling efficiency. When implanted into the right hemisphere of stroke mice, contralateral to the ischemic territory, a small amount of labeled cells were able to be tracked migrating to the lesion sites using a clinical MRI scanner (3 T). More impressively, even when administered intravenously, the labeled cells could also be monitored homing to the ischemic area. MRI observations were corroborated by histological studies of the brain tissues. Our study demonstrated that fmSiO4@SPIONs are highly effective for cell imaging and hold great promise for MRI cell tracking in future.

Advances of Researches on Improving the Stability of Foams by Nanoparticles

NASA Astrophysics Data System (ADS)

Wang, G.; Wang, K. L.; Lu, C. J.

2017-09-01

Recently, nano-tech made a change of traditional oil-gas exploration. Considering that foam fluid had a poor stability, investigators proposed to add nanoparticles to stabilize the foam fluid system. This paper described the mechanism of particles to improve the stability of the foam fluid in detail; and emphasized the synergistic effect between nanoparticles and surfactants and its effect on the foaming and foam stability of dispersions; and reviewed the latest applications of foam fluid that was stabilized by nanoparticle in enhancing oil-gas recovery, in which there are analysis that showed that the nanoparticles not only greatly increase the stability of the foam fluid, but also improve the efficiency of foam fluid; and lastly, forecasted the development of nanotechnology in petroleum areas.

Multi-functional Magnetic Nanoparticles for Magnetic Resonance Imaging and Cancer Therapy

PubMed Central

Yallapu, Murali M.; Othman, Shadi F.; Curtis, Evan T.; Gupta, Brij K.; Jaggi, Meena; Chauhan, Subhash C.

2010-01-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapuetic agent for cancer therapy. PMID:21167595

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Yallapu, Murali M; Othman, Shadi F; Curtis, Evan T; Gupta, Brij K; Jaggi, Meena; Chauhan, Subhash C

2011-03-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

Ultrahigh field MRI in clinical neuroimmunology: a potential contribution to improved diagnostics and personalised disease management.

PubMed

Sinnecker, Tim; Kuchling, Joseph; Dusek, Petr; Dörr, Jan; Niendorf, Thoralf; Paul, Friedemann; Wuerfel, Jens

2015-01-01

Conventional magnetic resonance imaging (MRI) at 1.5 Tesla (T) is limited by modest spatial resolution and signal-to-noise ratio (SNR), impeding the identification and classification of inflammatory central nervous system changes in current clinical practice. Gaining from enhanced susceptibility effects and improved SNR, ultrahigh field MRI at 7 T depicts inflammatory brain lesions in great detail. This review summarises recent reports on 7 T MRI in neuroinflammatory diseases and addresses the question as to whether ultrahigh field MRI may eventually improve clinical decision-making and personalised disease management.

Computational studies of steering nanoparticles with magnetic gradients

NASA Astrophysics Data System (ADS)

Aylak, Sultan Suleyman

Magnetic Resonance Imaging (MRI) guided nanorobotic systems that could perform diagnostic, curative, and reconstructive treatments in the human body at the cellular and subcellular level in a controllable manner have recently been proposed. The concept of a MRI-guided nanorobotic system is based on the use of a MRI scanner to induce the required external driving forces to guide magnetic nanocapsules to a specific target. However, the maximum magnetic gradient specifications of existing clinical MRI systems are not capable of driving magnetic nanocapsules against the blood flow. This thesis presents the visualization of nanoparticles inside blood vessel, Graphical User Interface (GUI) for updating file including initial parameters and demonstrating the simulation of particles and C++ code for computing magnetic forces and fluidic forces. The visualization and GUI were designed using Virtual Reality Modeling Language (VRML), MATLAB and C#. The addition of software for MRI-guided nanorobotic system provides simulation results. Preliminary simulation results demonstrate that external magnetic field causes aggregation of nanoparticles while they flow in the vessel. This is a promising result --in accordance with similar experimental results- and encourages further investigation on the nanoparticle-based self-assembly structures for use in nanorobotic drug delivery.

Segmentation of MRI Brain Images with an Improved Harmony Searching Algorithm.

PubMed

Yang, Zhang; Shufan, Ye; Li, Guo; Weifeng, Ding

2016-01-01

The harmony searching (HS) algorithm is a kind of optimization search algorithm currently applied in many practical problems. The HS algorithm constantly revises variables in the harmony database and the probability of different values that can be used to complete iteration convergence to achieve the optimal effect. Accordingly, this study proposed a modified algorithm to improve the efficiency of the algorithm. First, a rough set algorithm was employed to improve the convergence and accuracy of the HS algorithm. Then, the optimal value was obtained using the improved HS algorithm. The optimal value of convergence was employed as the initial value of the fuzzy clustering algorithm for segmenting magnetic resonance imaging (MRI) brain images. Experimental results showed that the improved HS algorithm attained better convergence and more accurate results than those of the original HS algorithm. In our study, the MRI image segmentation effect of the improved algorithm was superior to that of the original fuzzy clustering method.

Segmentation of MRI Brain Images with an Improved Harmony Searching Algorithm

PubMed Central

Yang, Zhang; Li, Guo; Weifeng, Ding

2016-01-01

The harmony searching (HS) algorithm is a kind of optimization search algorithm currently applied in many practical problems. The HS algorithm constantly revises variables in the harmony database and the probability of different values that can be used to complete iteration convergence to achieve the optimal effect. Accordingly, this study proposed a modified algorithm to improve the efficiency of the algorithm. First, a rough set algorithm was employed to improve the convergence and accuracy of the HS algorithm. Then, the optimal value was obtained using the improved HS algorithm. The optimal value of convergence was employed as the initial value of the fuzzy clustering algorithm for segmenting magnetic resonance imaging (MRI) brain images. Experimental results showed that the improved HS algorithm attained better convergence and more accurate results than those of the original HS algorithm. In our study, the MRI image segmentation effect of the improved algorithm was superior to that of the original fuzzy clustering method. PMID:27403428

Thin chitosan films containing super-paramagnetic nanoparticles with contrasting capability in magnetic resonance imaging.

PubMed

Farjadian, Fatemeh; Moradi, Sahar; Hosseini, Majid

2017-03-01

Magnetic nanoparticles have found application as MRI contrasting agents. Herein, chitosan thin films containing super-paramagnetic iron oxide nanoparticles (SPIONs) are evaluated in magnetic resonance imaging (MRI). To determine their contrasting capability, super-paramagnetic nanoparticles coated with citrate (SPIONs-cit) were synthesized. Then, chitosan thin films with different concentrations of SPIONs-cit were prepared and their MRI data (i.e., r 2 and r 2 *) was evaluated in an aqueous medium. The synthesized SPIONs-cit and chitosan/SPIONs-cit films were characterized by FTIR, EDX, XRD as well as VSM with the morphology evaluated by SEM and AFM. The nanoparticle sizes and distribution confirmed well-defined nanoparticles and thin films formation along with high contrasting capability in MRI. Images revealed well-dispersed uniform nanoparticles, averaging 10 nm in size. SPIONs-cit's hydrodynamic size averaged 23 nm in diameter. The crystallinity obeyed a chitosan and SPIONs pattern. The in vitro cellular assay of thin films with a novel route was performed within Hek293 cell lines showing that thin films can be biocompatible.

Non-Invasive Magnetic Resonance Imaging of Nanoparticle Migration and Water Velocity Inside Sandstone

NASA Astrophysics Data System (ADS)

Phoenix, V. R.; Shukla, M.; Vallatos, A.; Riley, M. S.; Tellam, J. H.; Holmes, W. M.

2015-12-01

Manufactured nanoparticles (NPs) are already utilized in a diverse array of applications, including cosmetics, optics, medical technology, textiles and catalysts. Problematically, once in the natural environment, NPs can have a wide range of toxic effects. To protect groundwater from detrimental NPs we must be able to predict nanoparticle movement within the aquifer. The often complex transport behavior of nanoparticles ensures the development of NP transport models is not a simple task. To enhance our understanding of NP transport processes, we utilize novel magnetic resonance imaging (MRI) which enables us to look inside the rock and image the movement of nanoparticles within. For this, we use nanoparticles that are paramagnetic, making them visible to the MRI and enabling us to collect spatially resolved data from which we can develop more robust transport models. In this work, a core of Bentheimer sandstone (3 x 7 cm) was saturated with water and imaged inside a 7Tesla Bruker Biospec MRI. Firstly the porosity of the core was mapped using a MSME MRI sequence. Prior to imaging NP transport, the velocity of water (in absence on nanoparticles) was mapped using an APGSTE-RARE sequence. Nano-magnetite nanoparticles were then pumped into the core and their transport through the core was imaged using a RARE sequence. These images were calibrated using T2 parameter maps to provide fully quantitative maps of nanoparticle concentration at regular time intervals throughout the column (T2 being the spin-spin relaxation time of 1H nuclei). This work demonstrated we are able to spatially resolve porosity, water velocity and nanoparticle movement, inside rock, using a single technique (MRI). Significantly, this provides us with a unique and powerful dataset from which we are now developing new models of nanoparticle transport.

Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

PubMed

Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

2018-01-01

Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

Co-encapsulation of magnetic nanoparticles and doxorubicin into biodegradable microcarriers for deep tissue targeting by vascular MRI navigation.

PubMed

Pouponneau, Pierre; Leroux, Jean-Christophe; Soulez, Gilles; Gaboury, Louis; Martel, Sylvain

2011-05-01

Magnetic tumor targeting with external magnets is a promising method to increase the delivery of cytotoxic agents to tumor cells while reducing side effects. However, this approach suffers from intrinsic limitations, such as the inability to target areas within deep tissues, due mainly to a strong decrease of the magnetic field magnitude away from the magnets. Magnetic resonance navigation (MRN) involving the endovascular steering of therapeutic magnetic microcarriers (TMMC) represents a clinically viable alternative to reach deep tissues. MRN is achieved with an upgraded magnetic resonance imaging (MRI) scanner. In this proof-of-concept preclinical study, the preparation and steering of TMMC which were designed by taking into consideration the constraints of MRN and liver chemoembolization are reported. TMMC were biodegradable microparticles loaded with iron-cobalt nanoparticles and doxorubicin (DOX). These particles displayed high saturation magnetization (Ms = 72 emu g(-1)), MRI tracking compatibility (strong contrast on T2∗-weighted images), appropriate size for the blood vessel embolization (∼50 μm), and sustained release of DOX (over several days). The TMMC were successfully steered in vitro and in vivo in the rabbit model. In vivo targeting of the right or left liver lobes was achieved by MRN through the hepatic artery located 4 cm beneath the skin. Parameters such as flow velocity, TMMC release site in the artery, magnetic gradient and TMMC properties, affected the steering efficiency. These data illustrate the potential of MRN to improve drug targeting in deep tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Polymer-functionalized nanoparticles for improving oil displacement

NASA Astrophysics Data System (ADS)

Fossati, Ana B.; Martins Alho, Miriam; Jacobo, Silvia E.

2018-03-01

This work focuses on the synthesis, functionalization, and characterization of magnetic nanoparticles to be used for improving the oil recovery in the oil exploitation industry. In this manuscript we explore three different types of hydrophobic/hydrophilic functionalization through a silanized particle: with styrene, with acrylic acid and with a copolymer of styrene and maleic acid. Further application of such nanoparticles dispersions (nanofluid) are discussed as the wetting and spreading behaviour of liquids on the solid surfaces change if the wettability of solid surface is altered. In order to investigate the influence of wettability alternation on enhancing oil recovery after nanofluid treatment, flushing oil experiment and contact angle measurement were conducted in our laboratory. The results indicated that nanofluid can produce a better flushing efficiency compared with brine solution, and the contact angles of oil phase increased from 13° to 37° after nanofluid treatment (0.005% w/w). We focus on the synthesis of magnetic iron oxide nanoparticles considering recovering possibility.

WE-FG-BRA-07: Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy

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

Detappe, A; Institut Lumiere-Matiere, Lyon, FR; Kunjachan, S

Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research. Methods:more » The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and nonhuman primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2–3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues. Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons. Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible

Rationally engineered polymeric cisplatin nanoparticle for improved antitumor efficacy

PubMed Central

Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Chitra, J; Amarasiriwardena; Lupoli, Nicola; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya

2011-01-01

The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While, this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) co-polymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibit an IC50 = 0.77 ± 0.11μM comparable to that of free cisplatin (IC50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and releases cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibited significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy. PMID:21576779

In vitro and in vivo MRI visualization of nanocomposite biodegradable microcapsules with tunable contrast.

PubMed

German, Sergey V; Bratashov, Daniil N; Navolokin, Nikita A; Kozlova, Anastasia A; Lomova, Maria V; Novoselova, Marina V; Burilova, Evgeniya A; Zyev, Victor V; Khlebtsov, Boris N; Bucharskaya, Alla B; Terentyuk, Georgy S; Amirov, Rustem R; Maslyakova, Galina N; Sukhorukov, Gleb B; Gorin, Dmitry A

2016-11-30

Microcapsules, made of biodegradable polymers, containing magnetite nanoparticles with tunable contrast in both the T1 and T2 MRI modes, were successfully prepared using a layer-by-layer approach. The MRI contrast of the microcapsules was shown to depend on the distance between magnetite nanoparticles in the polymeric layers, which is controlled by their concentration in the microcapsule shell. A fivefold increase in the average distance between the nanoparticles in the microcapsule shell led to a change in the intensity of the MR signal of 100% for both the T1 and T2 modes. Enzyme treatment of biodegradable shells resulted in a change of the microcapsules' MRI contrast. In vivo degradation of nanocomposite microcapsules concentrated in the liver after intravenous injection was demonstrated by MRI. This method can be used for the creation of a new generation of drug delivery systems, including drug depot, with combined navigation, visualization and remote activated release of bioactive substances in vivo.

A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy.

PubMed

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Wu, Hailiang; Terada, Yasuko; Saga, Tsuneo; Aoki, Ichio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2016-08-01

Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn(2+) within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn(2+) ions. Binding to proteins increases the relaxivity of Mn(2+) and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.

A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy

NASA Astrophysics Data System (ADS)

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Wu, Hailiang; Terada, Yasuko; Saga, Tsuneo; Aoki, Ichio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2016-08-01

Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn2+ within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn2+ ions. Binding to proteins increases the relaxivity of Mn2+ and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.

Improved dynamic MRI reconstruction by exploiting sparsity and rank-deficiency.

PubMed

Majumdar, Angshul

2013-06-01

In this paper we address the problem of dynamic MRI reconstruction from partially sampled K-space data. Our work is motivated by previous studies in this area that proposed exploiting the spatiotemporal correlation of the dynamic MRI sequence by posing the reconstruction problem as a least squares minimization regularized by sparsity and low-rank penalties. Ideally the sparsity and low-rank penalties should be represented by the l(0)-norm and the rank of a matrix; however both are NP hard penalties. The previous studies used the convex l(1)-norm as a surrogate for the l(0)-norm and the non-convex Schatten-q norm (0improvements over the previous studies by replacing the l(1)-norm sparsity penalty by the lp-norm. Thus, we reconstruct the dynamic MRI sequence by solving a least squares minimization problem regularized by l(p)-norm as the sparsity penalty and Schatten-q norm as the low-rank penalty. There are no efficient algorithms to solve the said problems. In this paper, we derive efficient algorithms to solve them. The experiments have been carried out on Dynamic Contrast Enhanced (DCE) MRI datasets. Both quantitative and qualitative analysis indicates the superiority of our proposed improvement over the existing methods. Copyright © 2013 Elsevier Inc. All rights reserved.

Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.

PubMed

Li, Li; ten Hagen, Timo L M; Bolkestein, Michiel; Gasselhuber, Astrid; Yatvin, Jeremy; van Rhoon, Gerard C; Eggermont, Alexander M M; Haemmerich, Dieter; Koning, Gerben A

2013-04-28

Accumulation of nanoparticles in solid tumors depends on their extravasation. However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery. Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow. The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models. Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~85 nm) accumulation by intravital confocal microscopy. Local hyperthermia at 41°C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models. A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration. After hyperthermia, the tumor vasculature remains permeable for 8h. We visualize gaps in the endothelial lining of up to 10 μm induced by HT. Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27.5 μm in radius from the vessel walls. Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia. In conclusion, a thermal dose of 41°C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration. These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Green synthesis of silver nanoparticles aimed at improving theranostics

NASA Astrophysics Data System (ADS)

Vedelago, José; Gomez, Cesar G.; Valente, Mauro; Mattea, Facundo

2018-05-01

Nowadays, the combination of diagnosis and therapy, known as theranostics, is one of the keys for an optimal treatment for cancer diseases. Theranostics can be significantly improved by incorporating metallic nanoparticles that are specifically delivered and accumulated in cancerous tissue. In this context, precise knowledge about dosimetric effects in nanoparticle-infused tissues as well as the detection and processing of emerging radiation are extremely important issues. In the last years the first studies on theranostic nanomaterials in gel dosimetry have been presented but there is still a broad field of study to explore. Most of gel dosimetric materials are extremely sensible to modifications in their composition, the addition of enhancers, metallic or inorganic charges can alter their stability and dosimetric properties; therefore, thorough studies must be made before the incorporation of any type of modifier. In this work, the synthesis of metallic nanoparticles suitable for gel dosimetry for x-ray applications is presented. A green synthesis process of silver nanoparticles coated with porcine skin gelatin by thermal reduction of silver nitrate is presented. Nanoparticles were obtained and purified for their application in gel dosimetry. Also, nanoparticles size distribution, reaction yield and the preliminar application as theranostic agents were tested in Fricke gel dosimetry in the keV range. The obtained nanoparticles were successfully used in theranostic applications acting as fluorescent agents and dose enhancers in X-ray beam irradiation simultaneously.

Interventional MRI: tapering improves the distal sensitivity of the loopless antenna.

PubMed

Qian, Di; El-Sharkawy, AbdEl-Monem M; Atalar, Ergin; Bottomley, Paul A

2010-03-01

The "loopless antenna" is an interventional MRI detector consisting of a tuned coaxial cable and an extended inner conductor or "whip". A limitation is the poor sensitivity afforded at, and immediately proximal to, its distal end, which is exacerbated by the extended whip length when the whip is uniformly insulated. It is shown here that tapered insulation dramatically improves the distal sensitivity of the loopless antenna by pushing the current sensitivity toward the tip. The absolute signal-to-noise ratio is numerically computed by the electromagnetic method-of-moments for three resonant 3-T antennae with no insulation, uniform insulation, and with linearly tapered insulation. The analysis shows that tapered insulation provides an approximately 400% increase in signal-to-noise ratio in trans-axial planes 1 cm from the tip and a 16-fold increase in the sensitive area as compared to an equivalent, uniformly insulated antenna. These findings are directly confirmed by phantom experiments and by MRI of an aorta specimen. The results demonstrate that numerical electromagnetic signal-to-noise ratio analysis can accurately predict the loopless detector's signal-to-noise ratio and play a central role in optimizing its design. The manifold improvement in distal signal-to-noise ratio afforded by redistributing the insulation should improve the loopless antenna's utility for interventional MRI. (c) 2010 Wiley-Liss, Inc.

Humid Heat Autoclaving of Hybrid Nanoparticles Achieved by Decreased Nanoparticle Concentration and Improved Nanoparticle Stability Using Medium Chain Triglycerides as a Modifier.

PubMed

Gou, Jingxin; Chao, Yanhui; Liang, Yuheng; Zhang, Ning; He, Haibing; Yin, Tian; Zhang, Yu; Xu, Hui; Tang, Xing

2016-09-01

Humid heat autoclaving is a facile technique widely used in the sterilization of injections, but the high temperature employed would destroy nanoparticles composed of biodegradable polymers. The aim of this study was to investigate whether incorporation of medium chain triglycerides (MCT) could stabilize nanoparticles composed of poly (ethylene glycol)-b-polycaprolactone (PEG-b-PCL) during autoclaving (121°C, 10 min). Polymeric nanoparticles with different MCT contents were prepared by dialysis. Block copolymer degradation was studied by GPC. The critical aggregation concentrations of nanoparticles at different temperatures were determined using pyrene fluorescence. The size, morphology and weight averaged molecular weight of pristine/autoclaved nanoparticles were studied using DLS, TEM and SLS, respectively. Drug loading content and release profile were determined using RP-HPLC. The protecting effect of MCT on nanoparticles was dependent on the amount of MCT incorporated. Nanoparticles with high MCT contents, which assumed an emulsion-like morphology, showed reduced block copolymer degradation and particle disassociation after incubation at 100°C for 24 h. Nanoparticles with high MCT content showed the lowest critical aggregation concentration (CAC) under either room temperature or 60°C and the lowest particle concentration among all samples. And the particle size, drug loading content, physical stability and release profile of nanoparticles with high MCT contents remained nearly unchanged after autoclaving. Incorporation of high amount of MCT changed the morphology of PEG-b-PCL based nanoparticles to an emulsion-like structure and the nanoparticles prepared could withstand autoclaving due to improved particle stability and decreased particle concentration caused by MCT incorporation.

Magnetic nanoparticles in magnetic resonance imaging and diagnostics.

PubMed

Rümenapp, Christine; Gleich, Bernhard; Haase, Axel

2012-05-01

Magnetic nanoparticles are useful as contrast agents for magnetic resonance imaging (MRI). Paramagnetic contrast agents have been used for a long time, but more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been discovered to influence MRI contrast as well. In contrast to paramagnetic contrast agents, SPIOs can be functionalized and size-tailored in order to adapt to various kinds of soft tissues. Although both types of contrast agents have a inducible magnetization, their mechanisms of influence on spin-spin and spin-lattice relaxation of protons are different. A special emphasis on the basic magnetism of nanoparticles and their structures as well as on the principle of nuclear magnetic resonance is made. Examples of different contrast-enhanced magnetic resonance images are given. The potential use of magnetic nanoparticles as diagnostic tracers is explored. Additionally, SPIOs can be used in diagnostic magnetic resonance, since the spin relaxation time of water protons differs, whether magnetic nanoparticles are bound to a target or not.

Aptamer-conjugated Magnetic Nanoparticles as Targeted Magnetic Resonance Imaging Contrast Agent for Breast Cancer.

PubMed

Keshtkar, Mohammad; Shahbazi-Gahrouei, Daryoush; Khoshfetrat, Seyyed Mehdi; Mehrgardi, Masoud A; Aghaei, Mahmoud

2016-01-01

Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe 3 O 4 @Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells. The ability of the synthesized nanoprobe to target specifically the nucleolin overexpressed cells was assessed with the MRI technique. Results show that the synthesized nanoprobe produced strongly darkened T 2 -weighted magnetic resonance (MR) images with 4T1 cells, whereas the MR images of HFFF-PI6 cells incubated with the nanoprobe are brighter, showing small changes compared to water. The results demonstrate that in a Fe concentration of 45 μg/mL, the nanoprobe reduced by 90% MR image intensity in 4T1 cells compared with the 27% reduction in HFFF-PI6 cells. Analysis of MR signal intensity showed statistically significant signal intensity difference between 4T1 and HFFF-PI6 cells treated with the nanoprobe. MRI experiments demonstrate the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of nucleolin-expressing breast cancer cells.

Length matters: Improved high field EEG-fMRI recordings using shorter EEG cables.

PubMed

Assecondi, Sara; Lavallee, Christina; Ferrari, Paolo; Jovicich, Jorge

2016-08-30

The use of concurrent EEG-fMRI recordings has increased in recent years, allowing new avenues of medical and cognitive neuroscience research; however, currently used setups present problems with data quality and reproducibility. We propose a compact experimental setup for concurrent EEG-fMRI at 4T and compare it to a more standard reference setup. The compact setup uses short EEG cables connecting to the amplifiers, which are placed right at the back of the head RF coil on a form-fitting extension force-locked to the patient MR bed. We compare the two setups in terms of sensitivity to MR-room environmental noise, interferences between measuring devices (EEG or fMRI), and sensitivity to functional responses in a visual stimulation paradigm. The compact setup reduces the system sensitivity to both external noise and MR-induced artefacts by at least 60%, with negligible EEG noise induced from the mechanical vibrations of the cryogenic cooling compression pump. The compact setup improved EEG data quality and the overall performance of MR-artifact correction techniques. Both setups were similar in terms of the fMRI data, with higher reproducibility for cable placement within the scanner in the compact setup. This improved compact setup may be relevant to MR laboratories interested in reducing the sensitivity of their EEG-fMRI experimental setup to external noise sources, setting up an EEG-fMRI workplace for the first time, or for creating a more reproducible configuration of equipment and cables. Implications for safety and ergonomics are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

One-pot synthesis of water-soluble superparamagnetic iron oxide nanoparticles and their MRI contrast effects in the mouse brains.

PubMed

Wang, Jun; Zhang, Baolin; Wang, Lei; Wang, Ming; Gao, Fabao

2015-03-01

Water-soluble superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the thermal decomposition of iron (III) acetylacetonate (Fe(acac)3) in the mixture of poly(ethylene glycol) (PEG) and poly(ethylene imine) (PEI). The average sizes of the SPIONs are in the range of 6-12nm, which could be tuned by adjusting the synthesis temperature and molecular weight of PEI. Benefiting from the coating of hydrophilic PEG and PEI, the resulted SPIONs showed excellent colloidal stability in deionized water and other physiological buffers. The XRD patterns indicate that the obtained SPIONs are magnetite. The PEG/PEI-SPIONs exhibited high r2/r1 ratio. In vivo magnetic resonance imaging (MRI) of the mouse brains after intravenous injection of the SPIONs showed their good contrast effect. Considering the facile fabrication process and excellent imaging performance of the water soluble PEG-SPIONs and PEG/PEI-SPIONs, it is believed that the SPIONs will find great potential in advanced MRI. Copyright © 2014 Elsevier B.V. All rights reserved.

Interleaved EPI based fMRI improved by multiplexed sensitivity encoding (MUSE) and simultaneous multi-band imaging.

PubMed

Chang, Hing-Chiu; Gaur, Pooja; Chou, Ying-hui; Chu, Mei-Lan; Chen, Nan-kuei

2014-01-01

Functional magnetic resonance imaging (fMRI) is a non-invasive and powerful imaging tool for detecting brain activities. The majority of fMRI studies are performed with single-shot echo-planar imaging (EPI) due to its high temporal resolution. Recent studies have demonstrated that, by increasing the spatial-resolution of fMRI, previously unidentified neuronal networks can be measured. However, it is challenging to improve the spatial resolution of conventional single-shot EPI based fMRI. Although multi-shot interleaved EPI is superior to single-shot EPI in terms of the improved spatial-resolution, reduced geometric distortions, and sharper point spread function (PSF), interleaved EPI based fMRI has two main limitations: 1) the imaging throughput is lower in interleaved EPI; 2) the magnitude and phase signal variations among EPI segments (due to physiological noise, subject motion, and B0 drift) are translated to significant in-plane aliasing artifact across the field of view (FOV). Here we report a method that integrates multiple approaches to address the technical limitations of interleaved EPI-based fMRI. Firstly, the multiplexed sensitivity-encoding (MUSE) post-processing algorithm is used to suppress in-plane aliasing artifacts resulting from time-domain signal instabilities during dynamic scans. Secondly, a simultaneous multi-band interleaved EPI pulse sequence, with a controlled aliasing scheme incorporated, is implemented to increase the imaging throughput. Thirdly, the MUSE algorithm is then generalized to accommodate fMRI data obtained with our multi-band interleaved EPI pulse sequence, suppressing both in-plane and through-plane aliasing artifacts. The blood-oxygenation-level-dependent (BOLD) signal detectability and the scan throughput can be significantly improved for interleaved EPI-based fMRI. Our human fMRI data obtained from 3 Tesla systems demonstrate the effectiveness of the developed methods. It is expected that future fMRI studies requiring high

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents.

PubMed

Patel, Daksha; Kell, Arnold; Simard, Benoit; Xiang, Bo; Lin, Hung Yu; Tian, Ganghong

2011-02-01

A new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-D,L-phenylalanine (DL-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex(®). Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r(2) relaxivity of these nanoparticles on coordination with Cu(2+) ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Surface Modification of Gd Nanoparticles with pH-Responsive Block Copolymers for Use As Smart MRI Contrast Agents.

PubMed

Zhu, Liping; Yang, Yuan; Farquhar, Kirsten; Wang, Jingjing; Tian, Chixia; Ranville, James; Boyes, Stephen G

2016-02-01

Despite recent advances in the understanding of fundamental cancer biology, cancer remains the second most common cause of death in the United States. One of the primary factors indicative of high cancer morbidity and mortality and aggressive cancer phenotypes is tumors with a low extracellular pH (pHe). Thus, the ability to measure tumor pHe in vivo using noninvasive and accurate techniques that also provide high spatiotemporal resolution has become increasingly important and is of great interest to researchers and clinicians. In an effort to develop a pH-responsive magnetic resonance imaging (MRI) contrast agent (CA) that has the potential to be used to measure tumor pHe, well-defined pH-responsive polymers, synthesized via reversible addition-fragmentation chain transfer polymerization, were attached to the surface of gadolinium-based nanoparticles (GdNPs) via a "grafting to" method after reduction of the thiocarbonylthio end groups. The successful modification of the GdNPs was verified by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and dynamic light scattering. The performance of the pH-responsive polymer modified GdNPs was then evaluated for potential use as smart MRI CAs via monitoring the relaxivity changes with changing environmental pH. The results suggested that the pH-responsive polymers can be used to effectively modify the GdNPs surface to prepare a smart contrast agent for MRI.

Multi-walled carbon/IF-WS2 nanoparticles with improved thermal properties

NASA Astrophysics Data System (ADS)

Xu, Fang; Almeida, Trevor P.; Chang, Hong; Xia, Yongde; Wears, M. Lesley; Zhu, Yanqiu

2013-10-01

A unique new class of core-shell structured composite nanoparticles, C-coated inorganic fullerene-like WS2 (IF-WS2) hollow nanoparticles, has been created for the first time in large quantities, by a continuous chemical vapour deposition method using a rotary furnace. Transmission electron microscopy and Raman characterisations of the resulting samples reveal that the composite nanoparticles exhibited a uniform shell of carbon coating, ranging from 2-5 nm on the IF-WS2 core, with little or no agglomeration. Importantly, thermogravimetric analysis and differential scanning calorimetry analysis confirm that their thermal stability against oxidation in air has been improved by about 70 °C, compared to the pristine IF-WS2, making these new C-coated IF-WS2 nanoparticles more attractive for critical engineering applications.A unique new class of core-shell structured composite nanoparticles, C-coated inorganic fullerene-like WS2 (IF-WS2) hollow nanoparticles, has been created for the first time in large quantities, by a continuous chemical vapour deposition method using a rotary furnace. Transmission electron microscopy and Raman characterisations of the resulting samples reveal that the composite nanoparticles exhibited a uniform shell of carbon coating, ranging from 2-5 nm on the IF-WS2 core, with little or no agglomeration. Importantly, thermogravimetric analysis and differential scanning calorimetry analysis confirm that their thermal stability against oxidation in air has been improved by about 70 °C, compared to the pristine IF-WS2, making these new C-coated IF-WS2 nanoparticles more attractive for critical engineering applications. Electronic supplementary information (ESI) available: Sketch of the rotary furnace, XRD pattern comparison of IF-WS2 and 2H WS2, XRD patterns of C-coated IF-WS2 (41-50°), and TGA and MS curves for pristine IF-WS2. See DOI: 10.1039/c3nr03844k

Magnetic nanoparticles for medical applications: Progress and challenges

NASA Astrophysics Data System (ADS)

Doaga, A.; Cojocariu, A. M.; Constantin, C. P.; Hempelmann, R.; Caltun, O. F.

2013-11-01

Magnetic nanoparticles present unique properties that make them suitable for applications in biomedical field such as magnetic resonance imaging (MRI), hyperthermia and drug delivery systems. Magnetic hyperthermia involves heating the cancer cells by using magnetic particles exposed to an alternating magnetic field. The cell temperature increases due to the thermal propagation of the heat induced by the nanoparticles into the affected region. In order to increase the effectiveness of the treatment hyperthermia can be combined with drug delivery techniques. As a spectroscopic technique MRI is used in medicine for the imaging of tissues especially the soft ones and diagnosing malignant or benign tumors. For this purpose ZnxCo1-xFe2O4 ferrite nanoparticles with x between 0 and 1 have been prepared by co-precipitation method. The cristallite size was determined by X-ray diffraction, while the transmission electron microscopy illustrates the spherical shape of the nanoparticles. Magnetic characterizations of the nanoparticles were carried out at room temperature by using a vibrating sample magnetometer. The specific absorption rate (SAR) was measured by calorimetric method at different frequencies and it has been observed that this value depends on the chemical formula, the applied magnetic fields and the frequency. The study consists of evaluating the images, obtained from an MRI facility, when the nanoparticles are dispersed in agar phantoms compared with the enhanced ones when Omniscan was used as contrast agent. Layer-by-layer technique was used to achieve the necessary requirement of biocompatibility. The surface of the magnetic nanoparticles was modified by coating it with oppositely charged polyelectrolites, making it possible for the binding of a specific drug.

A value-added exopolysaccharide as a coating agent for MRI nanoprobes

NASA Astrophysics Data System (ADS)

Palma, Susana I. C. J.; Rodrigues, Carlos A. V.; Carvalho, Alexandra; Morales, Maria Del Puerto; Freitas, Filomena; Fernandes, Alexandra R.; Cabral, Joaquim M. S.; Roque, Ana C. A.

2015-08-01

Fucopol, a fucose-containing exopolysaccharide (EPS) produced by the bacterium Enterobacter A47 DSM 23139 using glycerol as a carbon source, was employed as a new coating material for iron oxide magnetic nanoparticles (MNPs). The coated particles were assessed as nanoprobes for cell labeling by Magnetic Resonance Imaging (MRI). The MNPs were synthesized by a thermal decomposition method and transferred to an aqueous medium by a ligand-exchange reaction with meso-2,3-dimercaptosuccinic acid (DMSA). Covalent binding of EPS to DMSA-stabilized nanoparticles (MNP-DMSA) resulted in a hybrid magnetic-biopolymeric nanosystem (MNP-DMSA-EPS) with a hydrodynamic size of 170 nm, a negative surface charge under physiological conditions and transverse to longitudinal relaxivity ratio, r2/r1, of 148. In vitro studies with two human cell lines (colorectal carcinoma - HCT116 - and neural stem/progenitor cells - ReNcell VM) showed that EPS promotes internalization of nanoparticles in both cell lines. In vitro MRI cell phantoms showed a superior performance of MNP-DMSA-EPS in ReNcell VM, for which the iron dose-dependent MRI signal drop was obtained at relatively low iron concentrations (12-20 μg Fe per ml) and short incubation times. Furthermore, ReNcell VM multipotency was not affected by culture in the presence of MNP-DMSA or MNP-DMSA-EPS for 14 days. Our study suggests that Fucopol-coated MNPs represent useful cell labeling nanoprobes for MRI.Fucopol, a fucose-containing exopolysaccharide (EPS) produced by the bacterium Enterobacter A47 DSM 23139 using glycerol as a carbon source, was employed as a new coating material for iron oxide magnetic nanoparticles (MNPs). The coated particles were assessed as nanoprobes for cell labeling by Magnetic Resonance Imaging (MRI). The MNPs were synthesized by a thermal decomposition method and transferred to an aqueous medium by a ligand-exchange reaction with meso-2,3-dimercaptosuccinic acid (DMSA). Covalent binding of EPS to DMSA

Safety assessment of nanoparamagnetic contrast agents with different coatings for molecular MRI

NASA Astrophysics Data System (ADS)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Saffari, Mojtaba; Zohdiaghdam, Reza; Gorji, Ensieh

2013-04-01

Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (< 40 nm) but different coatings of diethyleneglycol (DEG) as Gd2O3-DEG and methoxy polyethylene glycol-silane (mPEG-silane: 550 and 2000 Dalton) as SPGO-mPEG-silane550 and SPGO-mPEG-silane2000, respectively, in the SK-MEL3 cell line, by light microscopy, MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and the LDH assay detecting lactate dehydrogenase activity. The viability values were not statistically different between the three nanoparticles and Gd-DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles.

PubMed

Lee, Amani L; Gee, Clifford T; Weegman, Bradley P; Einstein, Samuel A; Juelfs, Adam R; Ring, Hattie L; Hurley, Katie R; Egger, Sam M; Swindlehurst, Garrett; Garwood, Michael; Pomerantz, William C K; Haynes, Christy L

2017-06-27

Oxygen homeostasis is important in the regulation of biological function. Disease progression can be monitored by measuring oxygen levels, thus producing information for the design of therapeutic treatments. Noninvasive measurements of tissue oxygenation require the development of tools with minimal adverse effects and facile detection of features of interest. Fluorine magnetic resonance imaging ( 19 F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for anatomical imaging, cell tracking, and oxygen sensing. However, the highly hydrophobic and lipophobic properties of perfluorocarbons require the formation of emulsions for biological studies, though stabilizing these emulsions has been challenging. To enhance the stability and biological loading of perfluorocarbons, one option is to incorporate perfluorocarbon liquids into the internal space of biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19 F MRI detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles (UMNs) have large internal cavities (average = 1.8 cm 3 g -1 ), facilitating an average 17% loading efficiency of PFCs, meeting the threshold fluorine concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs have the highest equivalent nuclei per PFC molecule and a spin-lattice (T 1 ) relaxation-based oxygen sensitivity of 0.0032 mmHg -1 s -1 at 16.4 T. The option of loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell syntheses, allows for use of a broad range of PFC liquids from a single material. The biocompatible and tunable chemistry of UMNs combined with the intrinsic properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical imaging, cell tracking, and metabolic spectroscopy with improved stability.

Nanoparticles for Improving Cancer Diagnosis

PubMed Central

Chen, Hongmin; Zhen, Zipeng; Todd, Trever; Chu, Paul K.; Xie, Jin

2013-01-01

Despite the progress in developing new therapeutic modalities, cancer remains one of the leading diseases causing human mortality. This is mainly attributed to the inability to diagnose tumors in their early stage. By the time the tumor is confirmed, the cancer may have already metastasized, thereby making therapies challenging or even impossible. It is therefore crucial to develop new or to improve existing diagnostic tools to enable diagnosis of cancer in its early or even pre-syndrome stage. The emergence of nanotechnology has provided such a possibility. Unique physical and physiochemical properties allow nanoparticles to be utilized as tags with excellent sensitivity. When coupled with the appropriate targeting molecules, nanoparticle-based probes can interact with a biological system and sense biological changes on the molecular level with unprecedented accuracy. In the past several years, much progress has been made in applying nanotechnology to clinical imaging and diagnostics, and interdisciplinary efforts have made an impact on clinical cancer management. This article aims to review the progress in this exciting area with emphases on the preparation and engineering techniques that have been developed to assemble “smart” nanoprobes. PMID:24068857

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

PubMed Central

Estelrich, Joan; Sánchez-Martín, María Jesús; Busquets, Maria Antònia

2015-01-01

Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents. PMID:25834422

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

PubMed Central

Thanou, M.; Gedroyc, W.

2013-01-01

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. PMID:23738076

MRI-guided brachytherapy

PubMed Central

Tanderup, Kari; Viswanathan, Akila; Kirisits, Christian; Frank, Steven J.

2014-01-01

The application of MRI-guided brachytherapy has demonstrated significant growth during the last two decades. Clinical improvements in cervix cancer outcomes have been linked to the application of repeated MRI for identification of residual tumor volumes during radiotherapy. This has changed clinical practice in the direction of individualized dose administration, and mounting evidence of improved clinical outcome with regard to local control, overall survival as well as morbidity. MRI-guided prostate HDR and LDR brachytherapy has improved the accuracy of target and organs-at-risk (OAR) delineation, and the potential exists for improved dose prescription and reporting for the prostate gland and organs at risk. Furthermore, MRI-guided prostate brachytherapy has significant potential to identify prostate subvolumes and dominant lesions to allow for dose administration reflecting the differential risk of recurrence. MRI-guided brachytherapy involves advanced imaging, target concepts, and dose planning. The key issue for safe dissemination and implementation of high quality MRI-guided brachytherapy is establishment of qualified multidisciplinary teams and strategies for training and education. PMID:24931089

Improving of enzyme immunoassay for detection and quantification of the target molecules using silver nanoparticles

NASA Astrophysics Data System (ADS)

Syrvatka, Vasyl J.; Slyvchuk, Yurij I.; Rozgoni, Ivan I.; Gevkan, Ivan I.; Overchuk, Marta O.

2014-02-01

Modern routine enzyme immunoassays for detection and quantification of biomolecules have several disadvantages such as high cost, insufficient sensitivity, complexity and long-term execution. The surface plasmon resonance of silver nanoparticles gives reasons of creating new in the basis of simple, highly sensitive and low cost colorimetric assays that can be applied to the detection of small molecules, DNA, proteins and pollutants. The main aim of the study was the improving of enzyme immunoassay for detection and quantification of the target molecules using silver nanoparticles. For this purpose we developed method for synthesis of silver nanoparticles with hyaluronic acid and studied possibility of use these nanoparticles in direct determination of target molecules concentration (in particular proteins) and for improving of enzyme immunoassay. As model we used conventional enzyme immunoassays for determination of progesterone and estradiol concentration. We obtained the possibility to produce silver nanoparticles with hyaluronan homogeneous in size between 10 and 12 nm, soluble and stable in water during long term of storage using modified procedure of silver nanoparticles synthesis. New method allows to obtain silver nanoparticles with strong optical properties at the higher concentrations - 60-90 μg/ml with the peak of absorbance at the wavelength 400 nm. Therefore surface plasmon resonance of silver nanoparticles with hyaluronan and ultraviolet-visible spectroscopy provide an opportunity for rapid determination of target molecules concentration (especial protein). We used silver nanoparticles as enzyme carriers and signal enhancers. Our preliminary data show that silver nanoparticles increased absorbance of samples that allows improving upper limit of determination of estradiol and progesterone concentration.

Magnetic nanoparticles for medical applications: Progress and challenges

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

Doaga, A.; Cojocariu, A. M.; Constantin, C. P.

2013-11-13

Magnetic nanoparticles present unique properties that make them suitable for applications in biomedical field such as magnetic resonance imaging (MRI), hyperthermia and drug delivery systems. Magnetic hyperthermia involves heating the cancer cells by using magnetic particles exposed to an alternating magnetic field. The cell temperature increases due to the thermal propagation of the heat induced by the nanoparticles into the affected region. In order to increase the effectiveness of the treatment hyperthermia can be combined with drug delivery techniques. As a spectroscopic technique MRI is used in medicine for the imaging of tissues especially the soft ones and diagnosing malignantmore » or benign tumors. For this purpose Zn{sub x}Co{sub 1−x}Fe{sub 2}O{sub 4} ferrite nanoparticles with x between 0 and 1 have been prepared by co-precipitation method. The cristallite size was determined by X-ray diffraction, while the transmission electron microscopy illustrates the spherical shape of the nanoparticles. Magnetic characterizations of the nanoparticles were carried out at room temperature by using a vibrating sample magnetometer. The specific absorption rate (SAR) was measured by calorimetric method at different frequencies and it has been observed that this value depends on the chemical formula, the applied magnetic fields and the frequency. The study consists of evaluating the images, obtained from an MRI facility, when the nanoparticles are dispersed in agar phantoms compared with the enhanced ones when Omniscan was used as contrast agent. Layer-by-layer technique was used to achieve the necessary requirement of biocompatibility. The surface of the magnetic nanoparticles was modified by coating it with oppositely charged polyelectrolites, making it possible for the binding of a specific drug.« less

Synthesis of core-shell iron nanoparticles via a new (novel) approach

NASA Astrophysics Data System (ADS)

Chaudhary, Rakesh P.; Koymen, Ali R.

2014-03-01

Carbon-encapsulated iron (Fe) nanoparticles were synthesized by a newly developed method in toluene. Transmission Electron Microscopy (TEM) and High Resolution Transmission Electron Microscopy (HRTEM) of the as prepared sample reveal that core-shell nanostructures have been formed with Fe as core and graphitic carbon as shell. Fe nanoparticles with diameter 11nm to 102 nm are encapsulated by 6-8 nm thick graphitic carbon layers. There was no iron carbide formation observed between the Fe core and the graphitic shell. The Fe nanoparticles have body centered cubic (bcc) crystal structure. The magnetic hysteresis loop of the as synthesized powder at room temperature showed a saturation magnetization of 9 Am2 kg-1. After thermal treatment crystalline order of the samples improved and hence saturation magnetization increased to 24 Am2kg-1. We foresee that the carbon-encapsulated Fe nanoparticles are biologically friendly and could have potential applications in Magnetic Resonance Imaging (MRI) and Photothermal cancer therapy.

An update on clinical applications of magnetic nanoparticles for increasing the resolution of magnetic resonance imaging.

PubMed

Zeinali Sehrig, Fatemeh; Majidi, Sima; Asvadi, Sahar; Hsanzadeh, Arash; Rasta, Seyed Hossein; Emamverdy, Masumeh; Akbarzadeh, Jamshid; Jahangiri, Sahar; Farahkhiz, Shahrzad; Akbarzadeh, Abolfazl

2016-11-01

Today, technologies based on magnetic nanoparticles (MNPs) are regularly applied to biological systems with diagnostic or therapeutic aims. Nanoparticles made of the elements iron (Fe), gadolinium (Gd) or manganese (Mn) are generally used in many diagnostic applications performed under magnetic resonance imaging (MRI). Similar to molecular-based contrast agents, nanoparticles can be used to increase the resolution of imaging while offering well biocompatibility, poisonousness and biodistribution. Application of MNPs enhanced MRI sensitivity due to the accumulation of iron in the liver caused by discriminating action of the hepatobiliary system. The aim of this study is about the use, properties and advantages of MNPs in MRI.

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI

NASA Astrophysics Data System (ADS)

Pei, Linmin; Reza, Syed M. S.; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M.

2017-03-01

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. To model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI.

PubMed

Pei, Linmin; Reza, Syed M S; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M

2017-02-11

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. In order to model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

Multi-walled carbon/IF-WS2 nanoparticles with improved thermal properties.

PubMed

Xu, Fang; Almeida, Trevor P; Chang, Hong; Xia, Yongde; Wears, M Lesley; Zhu, Yanqiu

2013-11-07

A unique new class of core-shell structured composite nanoparticles, C-coated inorganic fullerene-like WS2 (IF-WS2) hollow nanoparticles, has been created for the first time in large quantities, by a continuous chemical vapour deposition method using a rotary furnace. Transmission electron microscopy and Raman characterisations of the resulting samples reveal that the composite nanoparticles exhibited a uniform shell of carbon coating, ranging from 2-5 nm on the IF-WS2 core, with little or no agglomeration. Importantly, thermogravimetric analysis and differential scanning calorimetry analysis confirm that their thermal stability against oxidation in air has been improved by about 70 °C, compared to the pristine IF-WS2, making these new C-coated IF-WS2 nanoparticles more attractive for critical engineering applications.

Linearization improves the repeatability of quantitative dynamic contrast-enhanced MRI.

PubMed

Jones, Kyle M; Pagel, Mark D; Cárdenas-Rodríguez, Julio

2018-04-01

The purpose of this study was to compare the repeatabilities of the linear and nonlinear Tofts and reference region models (RRM) for dynamic contrast-enhanced MRI (DCE-MRI). Simulated and experimental DCE-MRI data from 12 rats with a flank tumor of C6 glioma acquired over three consecutive days were analyzed using four quantitative and semi-quantitative DCE-MRI metrics. The quantitative methods used were: 1) linear Tofts model (LTM), 2) non-linear Tofts model (NTM), 3) linear RRM (LRRM), and 4) non-linear RRM (NRRM). The following semi-quantitative metrics were used: 1) maximum enhancement ratio (MER), 2) time to peak (TTP), 3) initial area under the curve (iauc64), and 4) slope. LTM and NTM were used to estimate K trans , while LRRM and NRRM were used to estimate K trans relative to muscle (R Ktrans ). Repeatability was assessed by calculating the within-subject coefficient of variation (wSCV) and the percent intra-subject variation (iSV) determined with the Gage R&R analysis. The iSV for R Ktrans using LRRM was two-fold lower compared to NRRM at all simulated and experimental conditions. A similar trend was observed for the Tofts model, where LTM was at least 50% more repeatable than the NTM under all experimental and simulated conditions. The semi-quantitative metrics iauc64 and MER were as equally repeatable as K trans and R Ktrans estimated by LTM and LRRM respectively. The iSV for iauc64 and MER were significantly lower than the iSV for slope and TTP. In simulations and experimental results, linearization improves the repeatability of quantitative DCE-MRI by at least 30%, making it as repeatable as semi-quantitative metrics. Copyright © 2017 Elsevier Inc. All rights reserved.

MRI-Based Computed Tomography Metal Artifact Correction Method for Improving Proton Range Calculation Accuracy

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

Park, Peter C.; Schreibmann, Eduard; Roper, Justin

2015-03-15

Purpose: Computed tomography (CT) artifacts can severely degrade dose calculation accuracy in proton therapy. Prompted by the recently increased popularity of magnetic resonance imaging (MRI) in the radiation therapy clinic, we developed an MRI-based CT artifact correction method for improving the accuracy of proton range calculations. Methods and Materials: The proposed method replaces corrupted CT data by mapping CT Hounsfield units (HU number) from a nearby artifact-free slice, using a coregistered MRI. MRI and CT volumetric images were registered with use of 3-dimensional (3D) deformable image registration (DIR). The registration was fine-tuned on a slice-by-slice basis by using 2D DIR.more » Based on the intensity of paired MRI pixel values and HU from an artifact-free slice, we performed a comprehensive analysis to predict the correct HU for the corrupted region. For a proof-of-concept validation, metal artifacts were simulated on a reference data set. Proton range was calculated using reference, artifactual, and corrected images to quantify the reduction in proton range error. The correction method was applied to 4 unique clinical cases. Results: The correction method resulted in substantial artifact reduction, both quantitatively and qualitatively. On respective simulated brain and head and neck CT images, the mean error was reduced from 495 and 370 HU to 108 and 92 HU after correction. Correspondingly, the absolute mean proton range errors of 2.4 cm and 1.7 cm were reduced to less than 2 mm in both cases. Conclusions: Our MRI-based CT artifact correction method can improve CT image quality and proton range calculation accuracy for patients with severe CT artifacts.« less

Electric-field responsive contrast agent based on liquid crystals and magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Mair, Lamar O.; Martinez-Miranda, Luz J.; Kurihara, Lynn K.; Nacev, Aleksandar; Hilaman, Ryan; Chowdhury, Sagar; Jafari, Sahar; Ijanaten, Said; da Silva, Claudian; Baker-McKee, James; Stepanov, Pavel Y.; Weinberg, Irving N.

2018-05-01

The properties of liquid crystal-magnetic nanoparticle composites have potential for sensing in the body. We study the response of a liquid crystal-magnetic nanoparticle (LC-MNP) composite to applied potentials of hundreds of volts per meter. Measuring samples using X-ray diffraction (XRD) and imaging composites using magnetic resonance imaging (MRI), we demonstrate that electric potentials applied across centimeter scale LC-MNP composite samples can be detected using XRD and MRI techniques.

Plasma-Functionalized Polytetrafluoroethylene Nanoparticles for Improved Wear in Lubricated Contact

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

Sharma, Vinay; Timmons, Richard; Erdemir, Ali

Plasma-functionalized polytetrafluoroethylene (PTFE) nanoparticles were employed to evaluate their utility in improving the lubrication property of a group III mineral oil with a significantly low amount of zinc dialkyl dithiophosphate (ZDDP). The particles were coated with two consecutive films; the initial coating contained silica to enhance amorphous glassy tribofilm formation, followed by a methacrylate film to protect the silica coating and enhance dispersibility in the oil. The functionalized nanoparticles were evaluated for their tribological performance using a high-frequency reciprocating rig, in a cylinder-on-flat configuration. The oil formulations containing ZDDP (350 ppm phosphorus level) and the functionalized nanoparticles resulted in dramaticmore » reductions in the friction coefficient and overall wear compared to the samples containing nonfunctionalized PTFE nanoparticles, ZDDP (350 ppm P), and samples devoid of nanoparticles but containing ZDDP with a 700 ppm P treat rate. XPS and XANES spectroscopy were employed to characterize the tribological films formed on the test samples. The samples with functionalized particles and ZDDP clearly exhibited tribofilms with Si- and F-doped polyphosphates of Zn coupled with the presence of ZnS at the metal-tribofilm interface. On the other hand, oils without the functionalized nanoparticles have oxides of Fe and to a lesser extent short-chain phosphates of Zn. The overall results suggest that the synergism between plasma-coated PTFE nanoparticles and ZDDP contributed to the development of protective tribofilms even at reduced amount of phosphorus in the oil. This new method of employing nanoparticles to deliver novel antifriction and antiwear chemistries at the tribological interfaces stands out as a promising approach to further reduce P levels in oils without compromising friction and wear performance.« less

ADAPTIVE REAL-TIME CARDIAC MRI USING PARADISE: VALIDATION BY THE PHYSIOLOGICALLY IMPROVED NCAT PHANTOM

PubMed Central

Sharif, Behzad; Bresler, Yoram

2013-01-01

Patient-Adaptive Reconstruction and Acquisition Dynamic Imaging with Sensitivity Encoding (PARADISE) is a dynamic MR imaging scheme that optimally combines parallel imaging and model-based adaptive acquisition. In this work, we propose the application of PARADISE to real-time cardiac MRI. We introduce a physiologically improved version of a realistic four-dimensional cardiac-torso (NCAT) phantom, which incorporates natural beat-to-beat heart rate and motion variations. Cardiac cine imaging using PARADISE is simulated and its performance is analyzed by virtue of the improved phantom. Results verify the effectiveness of PARADISE for high resolution un-gated real-time cardiac MRI and its superiority over conventional acquisition methods. PMID:24398475

A theranostic nanoplatform: magneto-gold@fluorescence polymer nanoparticles for tumor targeting T1&T2-MRI/CT/NIR fluorescence imaging and induction of genuine autophagy mediated chemotherapy.

PubMed

Wang, Guannan; Qian, Kun; Mei, Xifan

2018-06-14

Multifunctional nanoparticles, bearing low toxicity and tumor-targeting properties, coupled with multifunctional diagnostic imaging and enhanced treatment efficacy, have drawn tremendous attention due to their enormous potential for medical applications. Herein, we report a new kind of biocompatible and tumor-targeting magneto-gold@fluorescent polymer nanoparticle (MGFs-LyP-1), which is based on ultra-small magneto-gold (Fe 3 O 4 -Au) nanoparticles and NIR emissive fluorescent polymers by a solvent-mediated method. This kind of nanoparticle could be taken up efficiently and simultaneously serve for in vivo tumor targeting T 1 &T 2 -MRI/CT/near infrared (NIR) fluorescence bioimaging. Furthermore, the nanoparticles exhibit small size, higher tumor targeting accumulation, excellent cytocompatibility for long-term tracking, and no disturbing cell proliferation and differentiation. Moreover, clear and convincing evidence proves that as-synthesized MGFs-LyP-1 could elicit genuine autophagy via inducing autophagosome formation, which offers a definite synergistic effect to enhance cancer therapy with doxorubicin (DOX) at a nontoxic concentration through enhancement of the autophagy flux. Meanwhile, the as-prepared nanoparticles could be rapidly cleared from mice without any obvious organ impairment. The results indeed reveal a promising prospect of an MGFs-LyP-1 contrast agent with low toxicity and high efficiency for promising application in biomedicine.

Adaptable Near-Infrared Spectroscopy Fiber Array for Improved Coupling to Different Breast Sizes During Clinical MRI

PubMed Central

Mastanduno, Michael A.; El-Ghussein, Fadi; Jiang, Shudong; DiFlorio-Alexander, Roberta; Junqing, Xu; Hong, Yin; Pogue, Brian W.; Paulsen, Keith D.

2016-01-01

Rationale and Objectives Near-infrared spectroscopy (NIRS) of breast can provide functional information on the vascular and structural compartments of tissues in regions identified during simultaneous magnetic resonance imaging (MRI). NIRS can be acquired during dynamic contrast-enhanced MRI (DCE-MRI) to accomplish image-guided spectroscopy of the enhancing regions, potentially increasing the diagnostic specificity of the examination and reducing the number of biopsies performed as a result of inconclusive MRI breast imaging studies. Materials and Methods We combine synergistic attributes of concurrent DCE-MRI and NIRS with a new design of the clinical NIRS breast interface that couples to a standard MR breast coil and allows imaging of variable breast sizes. Spectral information from healthy volunteers and cancer patients is recovered, providing molecular information in regions defined by the segmented MR image volume. Results The new coupling system significantly improves examination utility by allowing improved coupling of the NIR fibers to breasts of all cup sizes and lesion locations. This improvement is demonstrated over a range of breast sizes (cup size A through D) and normal tissue heterogeneity using a group of eight healthy volunteers and two cancer patients. Lesions located in the axillary region and medial-posterior breast are now accessible to NIRS optodes. Reconstructed images were found to have biologically plausible hemoglobin content, oxygen saturation, and water and lipid fractions. Conclusions In summary, a new NIRS/MRI breast interface was developed to accommodate the variation in breast sizes and lesion locations that can be expected in clinical practice. DCE-MRI–guided NIRS quantifies total hemoglobin, oxygenation, and scattering in MR-enhancing regions, increasing the diagnostic information acquired from MR examinations. PMID:24439327

Real-time cellular and molecular dynamics of bi-metallic self-therapeutic nanoparticle in cancer cells

NASA Astrophysics Data System (ADS)

Vishwakarma, Sandeep Kumar; Bardia, Avinash; Lakkireddy, Chandrakala; Paspala, Syed Ameer Basha; Habeeb, Md. Aejaz; Khan, Aleem Ahmed

2018-02-01

Since last decades various kinds of nanoparticles have been functionalized to improve their biomedical applications. However, the biological effect of un-modified/non-functionalized bi-metallic magnetic nanoparticles remains under investigated. Herein we demonstrate a multifaceted non-functionalized bi-metallic inorganic Gd-SPIO nanoparticle which passes dual high MRI contrast and can kill the cancer cells through several mechanisms. The results of the present study demonstrate that Gd-SPIO nanoparticles have potential to induce cancer cell death by production of reactive oxygen species and apoptotic events. Furthermore, Gd-SPIO nanoparticles also enhance the expression levels of miRNA-199a and miRNA-181a-7p which results in decreased levels of cancer markers such as C-met, TGF-β and hURP. One very interesting finding of this study reveals side scatter-based real-time analysis of nanoparticle uptake in cancer cells using flow cytometry analysis. In conclusion, this study paves a way for future investigation of un-modified inorganic nanoparticles to purport enhanced therapeutic effect in combination with potential anti-tumor drugs/molecules in cancer cells.

Macrophages mediated diagnosis of rheumatoid arthritis using fibrin based magnetic nanoparticles as MRI contrast agents.

PubMed

Periyathambi, Prabu; Sastry, Thotapalli Parvathaleswara; Anandasadagopan, Suresh Kumar; Manickavasagam, Kanagavel

2017-01-01

A variety of bioimaging tools assists in the diagnosis and evaluation of rheumatoid arthritis (RA) and other osteoarthritis. However, detection of RA in the early stages by targeting its macrophages with suitable contrast agents will help in arresting the progression of the disease. In the present study, we investigated the effectiveness of using magnetic fibrin nanoparticles (MFNPs) conjugated with folic acid (FA-MFNPs) as a specific contrast agent to target the activated macrophages, which overexpress the folate receptors (FR) in the knee joints of rats with antigen-induced arthritis (AIA). FA-MFNPs were spherical with an average size of 18.3±1.6nm. In vitro studies have shown effective internalization of FA-MFNPs into the Raw264.7 macrophage cells. In vivo studies were carried out by injecting FA-MFNPs intravenously into the arthritic rats. The results showed enhanced MR imaging in the synovium of arthritic joints. Prussian blue histological staining confirmed uptake of FA-MFNPs by macrophages in the synovial tissue. The animal experiment results indicate that FA-MFNPs can be used as a specific MRI contrast agent in identifying phagocytic active macrophages in the synovial joints. Blood is the precursor source for synthesising the fibrin-based iron oxide (magnetic) nanoparticles (MFNPs) with diameters between 12 and 15nm. It has excellent superparamagnetic behaviour, biocompatibility, osteogenic potency, hemocompatibility, and biodegradable properties. MFNPs-based nanocomposites might be a promising contrast agent for bioimaging. Copyright © 2016 Elsevier B.V. All rights reserved.

Improving Efficiency of Multicrystalline Silicon and CIGS Solar Cells by Incorporating Metal Nanoparticles.

PubMed

Jeng, Ming-Jer; Chen, Zih-Yang; Xiao, Yu-Ling; Chang, Liann-Be; Ao, Jianping; Sun, Yun; Popko, Ewa; Jacak, Witold; Chow, Lee

2015-10-08

This work studies the use of gold (Au) and silver (Ag) nanoparticles in multicrystalline silicon (mc-Si) and copper-indium-gallium-diselenide (CIGS) solar cells. Au and Ag nanoparticles are deposited by spin-coating method, which is a simple and low cost process. The random distribution of nanoparticles by spin coating broadens the resonance wavelength of the transmittance. This broadening favors solar cell applications. Metal shadowing competes with light scattering in a manner that varies with nanoparticle concentration. Experimental results reveal that the mc-Si solar cells that incorporate Au nanoparticles outperform those with Ag nanoparticles. The incorporation of suitable concentration of Au and Ag nanoparticles into mc-Si solar cells increases their efficiency enhancement by 5.6% and 4.8%, respectively. Incorporating Au and Ag nanoparticles into CIGS solar cells improve their efficiency enhancement by 1.2% and 1.4%, respectively. The enhancement of the photocurrent in mc-Si solar cells is lower than that in CIGS solar cells, owing to their different light scattering behaviors and material absorption coefficients.

Improving Efficiency of Multicrystalline Silicon and CIGS Solar Cells by Incorporating Metal Nanoparticles

PubMed Central

Jeng, Ming-Jer; Chen, Zih-Yang; Xiao, Yu-Ling; Chang, Liann-Be; Ao, Jianping; Sun, Yun; Popko, Ewa; Jacak, Witold; Chow, Lee

2015-01-01

This work studies the use of gold (Au) and silver (Ag) nanoparticles in multicrystalline silicon (mc-Si) and copper-indium-gallium-diselenide (CIGS) solar cells. Au and Ag nanoparticles are deposited by spin-coating method, which is a simple and low cost process. The random distribution of nanoparticles by spin coating broadens the resonance wavelength of the transmittance. This broadening favors solar cell applications. Metal shadowing competes with light scattering in a manner that varies with nanoparticle concentration. Experimental results reveal that the mc-Si solar cells that incorporate Au nanoparticles outperform those with Ag nanoparticles. The incorporation of suitable concentration of Au and Ag nanoparticles into mc-Si solar cells increases their efficiency enhancement by 5.6% and 4.8%, respectively. Incorporating Au and Ag nanoparticles into CIGS solar cells improve their efficiency enhancement by 1.2% and 1.4%, respectively. The enhancement of the photocurrent in mc-Si solar cells is lower than that in CIGS solar cells, owing to their different light scattering behaviors and material absorption coefficients. PMID:28793599

Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances.

PubMed

Hola, Katerina; Markova, Zdenka; Zoppellaro, Giorgio; Tucek, Jiri; Zboril, Radek

2015-11-01

In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy.

PubMed

Schleich, Nathalie; Po, Chrystelle; Jacobs, Damien; Ucakar, Bernard; Gallez, Bernard; Danhier, Fabienne; Préat, Véronique

2014-11-28

Multifunctional nanoparticles combining therapy and imaging have the potential to improve cancer treatment by allowing personalized therapy. Herein, we aimed to compare in vivo different strategies in terms of targeting capabilities: (1) passive targeting via the EPR effect, (2) active targeting of αvβ3 integrin via RGD grafting, (3) magnetic targeting via a magnet placed on the tumor and (4) the combination of magnetic targeting and active targeting of αvβ3 integrin. For a translational approach, PLGA-based nanoparticles loaded with paclitaxel and superparamagnetic iron oxides were used. Electron Spin Resonance spectroscopy and Magnetic Resonance Imaging (MRI) were used to both quantify and visualize the accumulation of multifunctional nanoparticles into the tumors. We demonstrate that compared to untargeted or single targeted nanoparticles, the combination of both active strategy and magnetic targeting drastically enhanced (i) nanoparticle accumulation into the tumor tissue with an 8-fold increase compared to passive targeting (1.12% and 0.135% of the injected dose, respectively), (ii) contrast in MRI (imaging purpose) and (iii) anti-cancer efficacy with a median survival time of 22 days compared to 13 for the passive targeting (therapeutic purpose). Double targeting of nanoparticles to tumors by different mechanisms could be a promising translational approach for the management of therapeutic treatment and personalized therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Human-like collagen protein-coated magnetic nanoparticles with high magnetic hyperthermia performance and improved biocompatibility

NASA Astrophysics Data System (ADS)

Liu, Xiaoli; Zhang, Huan; Chang, Le; Yu, Baozhi; Liu, Qiuying; Wu, Jianpeng; Miao, Yuqing; Ma, Pei; Fan, Daidi; Fan, Haiming

2015-01-01

Human-like collagen (HLC)-coated monodispersed superparamagnetic Fe3O4 nanoparticles have been successfully prepared to investigate its effect on heat induction property and cell toxicity. After coating of HLC, the sample shows a faster rate of temperature increase under an alternating magnetic field although it has a reduced saturation magnetization. This is most probably a result of the effective heat conduction and good colloid stability due to the high charge of HLC on the surface. In addition, compared with Fe3O4 nanoparticles before coating with HLC, HLC-coated Fe3O4 nanoparticles do not induce notable cytotoxic effect at higher concentration which indicates that HLC-coated Fe3O4 nanoparticles has improved biocompatibility. Our results clearly show that Fe3O4 nanoparticles after coating with HLC not only possess effective heat induction for cancer treatment but also have improved biocompatibility for biomedicine applications.

Various ligand-coated ultrasmall gadolinium-oxide nanoparticles: Water proton relaxivity and in-vivo T1 MR image

NASA Astrophysics Data System (ADS)

Park, Ja Young; Kim, Sung June; Lee, Gang Ho; Jin, Seonguk; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok

2015-04-01

Surface coating of nanoparticles with ligands is essential in magnetic resonance imaging (MRI) because of solubility in water and biocompatibility. In this study, five organic molecules were used for surface coating of ultrasmall gadolinium-oxide (Gd2O3) nanoparticles (d avg = 2.0 nm). All of the samples showed large longitudinal (r1) and transverse (r2) water proton relaxivities with r2/r1 ratios that were close to one, corresponding to ideal conditions for T1 MRI contrast agents. Finally, in-vivo T1 MR images were acquired to prove the effectiveness of the surface-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent.

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals.

PubMed

Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

2016-08-19

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

PubMed Central

Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

2016-01-01

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3–24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining. PMID:27548152

Lanthanide-Doped Ceria Nanoparticles as Backside Coaters to Improve Silicon Solar Cell Efficiency.

PubMed

Hajjiah, Ali; Samir, Effat; Shehata, Nader; Salah, Mohamed

2018-05-23

This paper introduces lanthanide-doped ceria nanoparticles as silicon solar cell back-side coaters, showing their influence on the solar cell efficiency. Ceria nanoparticles can be synthesized to have formed oxygen vacancies (O-vacancies), which are associated with converting cerium ions from the Ce 4+ state ions to the Ce 3+ ones. These O-vacancies follow the rule of improving silicon solar cell conductivity through a hopping mechanism. Besides, under near-ultra violet (near-UV) excitation, the reduced trivalent cerium Ce 3+ ions are directly responsible for down converting the un-absorbed UV wavelengths to a resultant green photo-luminescence emission at ~520 nm, which is absorbed through the silicon solar cell’s active layer. Adding lanthanide elements such as Neodymium “Nd” as ceria nanoparticle dopants helps in forming extra oxygen vacancies (O-vacancies), followed by an increase in the number of Ce 4+ to Ce 3+ ion reductions, thus enhancing the conductivity and photoluminescence down conversion mechanisms. After introducing lanthanide-doped ceria nanoparticles on a silicon solar cell surface, a promising enhancement in the behavior of the solar cell current-voltage curve is observed, and the efficiency is improved by about 25% of its initial value due to the mutual impact of improving both electric conductivity and optical conversions.

Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI

PubMed Central

Fox, Michael D.; Qian, Tianyi; Madsen, Joseph R.; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-cong; Groppe, David M.; Mehta, Ashesh D.; Hong, Bo; Liu, Hesheng

2016-01-01

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20 years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach is demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. PMID:26408860

Improving left ventricular segmentation in four-dimensional flow MRI using intramodality image registration for cardiac blood flow analysis.

PubMed

Gupta, Vikas; Bustamante, Mariana; Fredriksson, Alexandru; Carlhäll, Carl-Johan; Ebbers, Tino

2018-01-01

Assessment of blood flow in the left ventricle using four-dimensional flow MRI requires accurate left ventricle segmentation that is often hampered by the low contrast between blood and the myocardium. The purpose of this work is to improve left-ventricular segmentation in four-dimensional flow MRI for reliable blood flow analysis. The left ventricle segmentations are first obtained using morphological cine-MRI with better in-plane resolution and contrast, and then aligned to four-dimensional flow MRI data. This alignment is, however, not trivial due to inter-slice misalignment errors caused by patient motion and respiratory drift during breath-hold based cine-MRI acquisition. A robust image registration based framework is proposed to mitigate such errors automatically. Data from 20 subjects, including healthy volunteers and patients, was used to evaluate its geometric accuracy and impact on blood flow analysis. High spatial correspondence was observed between manually and automatically aligned segmentations, and the improvements in alignment compared to uncorrected segmentations were significant (P < 0.01). Blood flow analysis from manual and automatically corrected segmentations did not differ significantly (P > 0.05). Our results demonstrate the efficacy of the proposed approach in improving left-ventricular segmentation in four-dimensional flow MRI, and its potential for reliable blood flow analysis. Magn Reson Med 79:554-560, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels.

PubMed

Sillerud, Laurel O

2016-01-01

We report the development, experimental verification, and application of a general theory called [Fe]MRI (pronounced fem-ree) for the non-invasive, quantitative molecular magnetic resonance imaging (MRI) of added magnetic nanoparticles or other magnetic contrast agents in biological tissues and other sites. [Fe]MRI can easily be implemented on any MRI instrument, requiring only measurements of the background nuclear magnetic relaxation times (T1, T2) of the tissue of interest, injection of the magnetic particles, and the subsequent acquisition of a pair of T1-weighted and T2-weighted images. These images, converted into contrast images, are subtracted to yield a contrast difference image proportional to the absolute nanoparticle, iron concentration, ([Fe]) image. [Fe]MRI was validated with the samples of superparamagnetic iron oxide nanoparticles (SPIONs) both in agarose gels and bound to human prostate tumor cells. The [Fe]MRI measurement of the binding of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs to PSMA-positive LNCaP and PSMA-negative DU145 cells in vitro allowed a facile discrimination among prostate tumor cell types based on their PSMA expression level. The low [Fe] detection limit of ~2 μM for SPIONs allows sensitive MRI of added iron at concentrations considerably below the US Food and Drug Administration's human iron dosage guidelines (<90 μM, 5 mg/kg).

Hybrid Core-Shell (HyCoS) Nanoparticles produced by Complex Coacervation for Multimodal Applications

NASA Astrophysics Data System (ADS)

Vecchione, D.; Grimaldi, A. M.; Forte, E.; Bevilacqua, Paolo; Netti, P. A.; Torino, E.

2017-03-01

Multimodal imaging probes can provide diagnostic information combining different imaging modalities. Nanoparticles (NPs) can contain two or more imaging tracers that allow several diagnostic techniques to be used simultaneously. In this work, a complex coacervation process to produce core-shell completely biocompatible polymeric nanoparticles (HyCoS) for multimodal imaging applications is described. Innovations on the traditional coacervation process are found in the control of the reaction temperature, allowing a speeding up of the reaction itself, and the production of a double-crosslinked system to improve the stability of the nanostructures in the presence of a clinically relevant contrast agent for MRI (Gd-DTPA). Through the control of the crosslinking behavior, an increase up to 6 times of the relaxometric properties of the Gd-DTPA is achieved. Furthermore, HyCoS can be loaded with a high amount of dye such as ATTO 633 or conjugated with a model dye such as FITC for in vivo optical imaging. The results show stable core-shell polymeric nanoparticles that can be used both for MRI and for optical applications allowing detection free from harmful radiation. Additionally, preliminary results about the possibility to trigger the release of a drug through a pH effect are reported.

PET/MRI for neurologic applications.

PubMed

Catana, Ciprian; Drzezga, Alexander; Heiss, Wolf-Dieter; Rosen, Bruce R

2012-12-01

PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation of the measured signals, creating opportunities impossible to realize using stand-alone instruments. This paper reviews the methodologic improvements and potential neurologic and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MRI data to improve the PET data quantification. On the MRI side, we present how improved PET quantification can be used to validate several MRI techniques. Finally, we describe promising research, translational, and clinical applications that can benefit from these advanced tools.

Composite iron oxide-Prussian blue nanoparticles for magnetically guided T1-weighted magnetic resonance imaging and photothermal therapy of tumors.

PubMed

Kale, Shraddha S; Burga, Rachel A; Sweeney, Elizabeth E; Zun, Zungho; Sze, Raymond W; Tuesca, Anthony; Subramony, J Anand; Fernandes, Rohan

2017-01-01

Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe 3 O 4 @GdPB) as a novel theranostic agent for T 1 -weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe 3 O 4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe 3 O 4 @GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe 3 O 4 @GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T 1 -weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe 3 O 4 @GdPB nanoparticles to function as effective theranostic agents.

Composite iron oxide–Prussian blue nanoparticles for magnetically guided T1-weighted magnetic resonance imaging and photothermal therapy of tumors

PubMed Central

Kale, Shraddha S; Burga, Rachel A; Sweeney, Elizabeth E; Zun, Zungho; Sze, Raymond W; Tuesca, Anthony; Subramony, J Anand; Fernandes, Rohan

2017-01-01

Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe3O4@GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T1-weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe3O4@GdPB nanoparticles to function as effective theranostic agents. PMID:28919744

Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy.

PubMed

Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

2017-06-01

The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans. In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development. Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.

Gold and Iron-Gold Nanoparticles for Intracellular Tracking and in Vivo Medical Applicatons

NASA Astrophysics Data System (ADS)

Fu, Wei

2005-03-01

We have fabricated Au and Fe-Au nanoparticles for potential use in ex vivo experiments such as intracellular tracking, as well as a variety of in vivo medical applications. In order to improve their targeting potential, circulation time and flexibility, gold NPs were surface modified using a hetero-bifunctional poly(ethylene glycol) (PEG, MW 1,500) spacers. A coumarin-PEG-gold NP complex was formed and cell viability studies and optical fluorescence experiments were carried out demonstrating the use of these surface-modified gold NPs for drug delivery, gene therapy and cell trafficking experiments. Fe-Au nanoparticles were also fabricated and show significant contrast enhancement in MRI studies through a substantial reduction of the T2 relaxation time.

Preparation of astaxanthin-loaded DNA/chitosan nanoparticles for improved cellular uptake and antioxidation capability.

PubMed

Wang, Qian; Zhao, Yingyuan; Guan, Lei; Zhang, Yaping; Dang, Qifeng; Dong, Ping; Li, Jing; Liang, Xingguo

2017-07-15

DNA/chitosan co-assemblies were initially used as nanocarriers for efficient astaxanthin encapsulation and delivery. The obtained astaxanthin-loaded DNA/chitosan (ADC) colloidal system was transparent and homogenous, with astaxanthin content up to 65μg/ml. Compared to free astaxanthin, ADC nanoparticles with an astaxanthin concentration as low as 3.35nM still showed a more powerful cytoprotective effect on H 2 O 2 -induced oxidative cell damage, and improved cell viability from 49.9% to 61.9%. The ROS scavenging efficiency of ADC nanoparticles was as high as 54.3%, which was 2-fold higher than that of free astaxanthin. Besides this, ADC nanoparticles were easily engulfed by Caco-2 cells in a short time, indicating that the encapsulated astaxanthin could be absorbed through endocytosis by intestinal epithelial cells. The improved antioxidation capability and facilitated cellular uptake enabled the ADC nanoparticles to be good candidates for efficient delivery and absorption of astaxanthin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carbodiimide versus click chemistry for nanoparticle surface functionalization: a comparative study for the elaboration of multimodal superparamagnetic nanoparticles targeting αvβ3 integrins.

PubMed

Bolley, Julie; Guenin, Erwann; Lievre, Nicole; Lecouvey, Marc; Soussan, Michael; Lalatonne, Yoann; Motte, Laurence

2013-11-26

Superparamagnetic fluorescent nanoparticles targeting αvβ3 integrins were elaborated using two methodologies: carbodiimide coupling and click chemistries (CuACC and thiol-yne). The nanoparticles are first functionalized with hydroxymethylenebisphonates (HMBP) bearing carboxylic acid or alkyne functions. Then, a large number of these reactives functions were used for the covalent coupling of dyes, poly(ethylene glycol) (PEG), and cyclic RGD. Several methods were used to characterize the nanoparticle surface functionalization, and the magnetic properties of these contrast agents were studied using a 1.5 T clinical MRI. The affinity toward integrins was evidenced by solid-phase receptor-binding assay. In addition to their chemoselective natures, click reactions were shown to be far more efficient than the carbodiimide coupling. The grafting increase was shown to enhance targeting affinity to integrin without imparing MRI and fluorescent properties.

Self-Assembled Superparamagnetic Iron Oxide Nanoclusters for Universal Cell Labeling and MRI

NASA Astrophysics Data System (ADS)

Chen, Shuzhen; Zhang, Jun; Jiang, Shengwei; Lin, Gan; Luo, Bing; Yao, Huan; Lin, Yuchun; He, Chengyong; Liu, Gang; Lin, Zhongning

2016-05-01

Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in a variety of biomedical applications, especially as contrast agents for magnetic resonance imaging (MRI) and cell labeling. In this study, SPIO nanoparticles were stabilized with amphiphilic low molecular weight polyethylenimine (PEI) in an aqueous phase to form monodispersed nanocomposites with a controlled clustering structure. The iron-based nanoclusters with a size of 115.3 ± 40.23 nm showed excellent performance on cellular uptake and cell labeling in different types of cells, moreover, which could be tracked by MRI with high sensitivity. The SPIO nanoclusters presented negligible cytotoxicity in various types of cells as detected using MTS, LDH, and flow cytometry assays. Significantly, we found that ferritin protein played an essential role in protecting stress from SPIO nanoclusters. Taken together, the self-assembly of SPIO nanoclusters with good magnetic properties provides a safe and efficient method for universal cell labeling with noninvasive MRI monitoring capability.

MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients

PubMed Central

Nichols-Vinueza, Diana X.; White, Matthew T.; Powell, Andrew J.; Banka, Puja; Neufeld, Ellis J.

2017-01-01

Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan®) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care. PMID:24652616

Aqueous synthesis of polyhedral “brick-like” iron oxide nanoparticles for hyperthermia and T2 MRI contrast enhancement†

PubMed Central

Worden, Matthew; Bruckman, Michael A.; Kim, Min-Ho; Steinmetz, Nicole F.; Kikkawa, James M.; LaSpina, Catherine

2015-01-01

A low temperature, aqueous synthesis of polyhedral iron oxide nanoparticles (IONPs) is presented. The modification of the co-precipitation hydrolysis method with Triton X surfactants results in the formation of crystalline polyhedral particles. The particles are herein termed iron oxide “nanobricks” (IONBs) as the variety of particles made are all variations on a simple “brick-like” rhombohedral shape as evaluated by TEM. These IONBs can be easily coated with hydrophilic silane ligands, allowing them to be dispersed in aqueous media. The dispersed particles are investigated for potential applications as hyperthermia and T2 MRI contrast agents. The results demonstrate that the IONBs perform better than comparable spherical IONPs in both applications, and show r2 values amongst the highest for iron oxide based materials reported in the literature. PMID:26693011

Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

PubMed Central

Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

2012-01-01

Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

Magneto-reactance based detection of MnO nanoparticle-embedded Lewis lung carcinoma cells

NASA Astrophysics Data System (ADS)

Devkota, J.; Howell, M.; Mukherjee, P.; Srikanth, H.; Mohapatra, S.; Phan, M. H.

2015-05-01

We demonstrate the capacity of detecting magnetically weak manganese oxide (MnO) nanoparticles and the Lewis lung carcinoma (LLC) cancer cells that have taken up these nanoparticles using a novel biosensor based on the magneto-reactance (MX) effect of a soft ferromagnetic amorphous ribbon with a microhole-patterned surface. While the magnetic moment of the MnO nanoparticles is relatively small, and a magneto-impedance based sensor fails to detect them in solution (0.05 mg/ml manganese oxide lipid micellar nanoparticles) and inside cells at low concentrations (8.25 × 104 cells/ml), the detection of these nanoparticles and the LLC cells containing them is achieved with the MX-based sensor, which, respectively, reaches the detection sensitivity of ˜3.6% and 2.8% as compared to the blank cells. Since the MnO nanoparticles are a promising contrast agent for magnetic resonance imaging (MRI) of lung cells, the MX-based biosensing technique can be developed as a pre-detection method for MRI of lung cancer cells.

Effective cellular internalization, cell cycle arrest and improved pharmacokinetics of Tamoxifen by cholesterol based lipopolymeric nanoparticles.

PubMed

Mazumdar, Samrat; Italiya, Kishan S; Sharma, Saurabh; Chitkara, Deepak; Mittal, Anupama

2018-05-30

The present study aims at the development of cholesterol based lipopolymeric nanoparticles for improved entrapment, better cell penetration and improved pharmacokinetics of Tamoxifen (TMX). Self-assembling cholesterol grafted lipopolymer, mPEG-b-(CB-{g-chol}-co-LA) was synthesized from poly(ethyleneglycol)-block-2-methyl-2-carboxyl-propylenecarboxylic acid-co-poly (l-lactide) [mPEG-b-(CB-{g-COOH}-co-LA)] copolymer followed by carbodiimide coupling for attaching cholesterol. Lipopolymeric nanoparticles were prepared using o/w solvent evaporation technique, which were subsequently characterized to determine its particle size, entrapment efficiency, release pattern and compared with mPEG-PLA nanoparticles. Further, in order to assess the in vitro efficacy, cytotoxicity studies, uptake, apoptosis assay and cell cycle analysis were performed in breast cancer cell lines (MCF-7 and 4T1). Finally, the pharmacokinetic profile of TMX loaded mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles was also performed. TMX loaded lipopolymeric nanoparticles of particle size 151.25 ± 3.74 (PDI 0.123) and entrapment efficiency of 73.62 ± 3.08% were formulated. The haemolytic index, protein binding and in vitro drug release of the optimized nanoparticles were found to be comparable to that of the TMX loaded mPEG-PLA nanoparticles. Lipopolymeric nanoparticles demonstrated improved IC 50 values in breast cancer cells (22.2 μM in 4T1; 18.8 μM in MCF-7) than free TMX (27.6 μM and 23.5 μM respectively) and higher uptake efficiency. At IC 50 values, TMX loaded lipopolymeric nanoparticles induced apoptosis and cell cycle arrest (G 0 /G 1 phase) to similar extent as that of free drug. Pharmacokinetic studies indicated ∼2.5-fold increase in the half-life (t 1/2 ) (p < 0.001) and ∼2.7-fold (p < 0.001) increase in the mean residence time (MRT) of TMX following incorporation into lipopolymeric nanoparticles. Thus, mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric

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.

Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects

NASA Astrophysics Data System (ADS)

Xu, He-Lin; Mao, Kai-Li; Huang, Yin-Ping; Yang, Jing-Jing; Xu, Jie; Chen, Pian-Pian; Fan, Zi-Liang; Zou, Shuang; Gao, Zheng-Zheng; Yin, Jia-Yu; Xiao, Jian; Lu, Cui-Tao; Zhang, Bao-Lin; Zhao, Ying-Zheng

2016-07-01

Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g-1. The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the

CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

PubMed

Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

2016-01-01

Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics.

PubMed

Huang, Yinping; Mao, Kaili; Zhang, Baolin; Zhao, Yingzheng

2017-01-01

Monodispersed SPIONs (superparamagnetic iron oxide nanoparticles) co-coated with PEG and PEI polymers were prepared by an improved polyol method. To accomplish cancer-specific targeting properties, FA (folic acid) was then modified on the SPIONs via EDC/NHS method (FA-SPIONs). Doxorubicin (DOX) as an example anticancer drug was loaded within FA-SPIONs (DOX@FA-SPIONs), the DOX release rate of DOX@FA-SPIONs was much high in low pH PBS. The SPIONs, FA-SPIONs and DOX@FA-SPIONs with mean hydrodynamic diameters of 23, 40 and 67nm, respectively, performed excellent colloidal stability in PBS. Confocal laser scanning microscope (CLSM) study implicates that the DOX@FA-SPIONs target MCF-7 cells efficiently through the FA receptor-mediated endocytosis. DOX@FA-SPIONs were tested in nude mice with xenograft MCF-7 breast tumor though tail intravenous injection and were found inhibiting tumor growth more efficiently. The application of a magnetic field (MF) greatly improved the growth inhibiting efficiencies of DOX@FA-SPIONs on MCF-7 cells in vitro and on xenograft MCF-7 breast tumor of nude mice in vivo. The aggregation of SPIONs in tumor was monitored by magnetic resonance imaging (MRI) as the DOX@FA-SPIONs exhibited high r 2 relaxivity (81.77mM -1 S -1 ). Histology on liver, Lung, kidney and heart in mice showed no significant toxicity of DOX@FA-SPIONs on mice organs after 35-day treatment. The FA-SPIONs are a high efficient drug delivery nanoplatform for advanced cancer theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex grafted onto gold nanoparticles.

PubMed

Mogilireddy, Vijetha; Déchamps-Olivier, Isabelle; Alric, Christophe; Laurent, Gautier; Laurent, Sophie; Vander Elst, Luce; Muller, Robert; Bazzi, Rana; Roux, Stéphane; Tillement, Olivier; Chuburu, Françoise

2015-01-01

Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd(3+) complexes and greatly enhanced their kinetic inertness. Copyright © 2014 John Wiley & Sons, Ltd.

Magnetic Particle Imaging (MPI) for NMR and MRI researchers

NASA Astrophysics Data System (ADS)

Saritas, Emine U.; Goodwill, Patrick W.; Croft, Laura R.; Konkle, Justin J.; Lu, Kuan; Zheng, Bo; Conolly, Steven M.

2013-04-01

Magnetic Particle Imaging (MPI) is a new tracer imaging modality that is gaining significant interest from NMR and MRI researchers. While the physics of MPI differ substantially from MRI, it employs hardware and imaging concepts that are familiar to MRI researchers, such as magnetic excitation and detection, pulse sequences, and relaxation effects. Furthermore, MPI employs the same superparamagnetic iron oxide (SPIO) contrast agents that are sometimes used for MR angiography and are often used for MRI cell tracking studies. These SPIOs are much safer for humans than iodine or gadolinium, especially for Chronic Kidney Disease (CKD) patients. The weak kidneys of CKD patients cannot safely excrete iodine or gadolinium, leading to increased morbidity and mortality after iodinated X-ray or CT angiograms, or after gadolinium-MRA studies. Iron oxides, on the other hand, are processed in the liver, and have been shown to be safe even for CKD patients. Unlike the “black blood” contrast generated by SPIOs in MRI due to increased T2∗ dephasing, SPIOs in MPI generate positive, “bright blood” contrast. With this ideal contrast, even prototype MPI scanners can already achieve fast, high-sensitivity, and high-contrast angiograms with millimeter-scale resolutions in phantoms and in animals. Moreover, MPI shows great potential for an exciting array of applications, including stem cell tracking in vivo, first-pass contrast studies to diagnose or stage cancer, and inflammation imaging in vivo. So far, only a handful of prototype small-animal MPI scanners have been constructed worldwide. Hence, MPI is open to great advances, especially in hardware, pulse sequence, and nanoparticle improvements, with the potential to revolutionize the biomedical imaging field.

Improved thermal stability of oxide-supported naked gold nanoparticles by ligand-assisted pinning

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

Moreno, C; Divins, N. J.; Gazquez, Jaume

We report a method to improve the thermal stability, up to 900 C, of bare-metal (naked) gold nanoparticles supported on top of SiO{sub 2} and SrTiO{sub 3} substrates via ligand-assisted pinning. This approach leads to monodisperse naked gold nanoparticles without significant sintering after thermal annealing in air at 900 C. The ligand-assisted pinning mechanism is described.

Music-based magnetic resonance fingerprinting to improve patient comfort during MRI examinations.

PubMed

Ma, Dan; Pierre, Eric Y; Jiang, Yun; Schluchter, Mark D; Setsompop, Kawin; Gulani, Vikas; Griswold, Mark A

2016-06-01

Unpleasant acoustic noise is a drawback of almost every MRI scan. Instead of reducing acoustic noise to improve patient comfort, we propose a technique for mitigating the noise problem by producing musical sounds directly from the switching magnetic fields while simultaneously quantifying multiple important tissue properties. MP3 music files were converted to arbitrary encoding gradients, which were then used with varying flip angles and repetition times in a two- and three-dimensional magnetic resonance fingerprinting (MRF) examination. This new acquisition method, named MRF-Music, was used to quantify T1 , T2 , and proton density maps simultaneously while providing pleasing sounds to the patients. MRF-Music scans improved patient comfort significantly during MRI examinations. The T1 and T2 values measured from phantom are in good agreement with those from the standard spin echo measurements. T1 and T2 values from the brain scan are also close to previously reported values. MRF-Music sequence provides significant improvement in patient comfort compared with the MRF scan and other fast imaging techniques such as echo planar imaging and turbo spin echo scans. It is also a fast and accurate quantitative method that quantifies multiple relaxation parameters simultaneously. Magn Reson Med 75:2303-2314, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Improving Functional MRI Registration Using Whole-Brain Functional Correlation Tensors.

PubMed

Zhou, Yujia; Yap, Pew-Thian; Zhang, Han; Zhang, Lichi; Feng, Qianjin; Shen, Dinggang

2017-09-01

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) largely rely on the accurate inter-subject registration of functional areas. This is typically achieved through registration of the corresponding T1-weighted MR images with more structural details. However, accumulating evidence has suggested that such strategy cannot well-align functional regions which are not necessarily confined by the anatomical boundaries defined by the T1-weighted MR images. To mitigate this problem, various registration algorithms based directly on rs-fMRI data have been developed, most of which have utilized functional connectivity (FC) as features for registration. However, most of the FC-based registration methods usually extract the functional features only from the thin and highly curved cortical grey matter (GM), posing a great challenge in accurately estimating the whole-brain deformation field. In this paper, we demonstrate that the additional useful functional features can be extracted from brain regions beyond the GM, particularly, white-matter (WM) based on rs-fMRI, for improving the overall functional registration. Specifically, we quantify the local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals, modeled by functional correlation tensors (FCTs), in both GM and WM. Functional registration is then performed based on multiple components of the whole-brain FCTs using a multichannel Large Deformation Diffeomorphic Metric Mapping (mLDDMM) algorithm. Experimental results show that our proposed method achieves superior functional registration performance, compared with other conventional registration methods.

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

PubMed

Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

2016-09-01

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid-polymer hybrid nanoparticles.

PubMed

Wu, Bo; Lu, Shu-Ting; Deng, Kai; Yu, Hui; Cui, Can; Zhang, Yang; Wu, Ming; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

2017-01-01

In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo.

Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

NASA Astrophysics Data System (ADS)

Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

2013-08-01

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics.

PubMed

Ahmed, Osama A A; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid-liquid phase separation method, according to the Box-Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance.

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics

PubMed Central

Ahmed, Osama AA; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid–liquid phase separation method, according to the Box–Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance. PMID:25670883

Improving colorimetric assays through protein enzyme-assisted gold nanoparticle amplification.

PubMed

Xie, Xiaoji; Xu, Wei; Liu, Xiaogang

2012-09-18

The discovery of the DNA-mediated assembly of gold nanoparticles was a great moment in the history of science; this understanding and chemical control enabled the rational design of functional nanomaterials as novel probes in biodetection. In contrast with conventional probes such as organic dyes, gold nanoparticles exhibit high photostability and unique size-dependent optical properties. Because of their high extinction coefficients and strong distance dependent optical properties, these nanoparticles have emerged over the past decade as a promising platform for rapid, highly sensitive colorimetric assays that allow for the visual detection of low concentrations of metal ions, small molecules, and biomacromolecules. These discoveries have deepened our knowledge of biological phenomena and facilitated the development of many new diagnostic and therapeutic tools. Despite these many advances and continued research efforts, current nanoparticle-based colorimetric detection systems still suffer from several drawbacks, such as limited sensitivity and selectivity. This Account describes the recent development of colorimetric assays based on protein enzyme-assisted gold nanoparticle amplification. The benefits of such detection systems include significantly improved detection sensitivity and selectivity. First, we discuss the general design of enzyme-modified nanoparticle systems in colorimetric assays. We show that a quantitative understanding of the unique properties of different enzymes is paramount for effective biological assays. We then examine the assays for nucleic acid detection based on different types of enzymes, including endonucleases, ligases, and polymerases. For each of these assays, we identify the underlying principles that contribute to the enhanced detection capability of nanoparticle systems and illustrate them with selected examples. Furthermore, we demonstrate that the combination of gold nanoparticles and specific enzymes can probe enzyme dynamics

Correction of MRI-induced geometric distortions in whole-body small animal PET-MRI

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

Frohwein, Lynn J., E-mail: frohwein@uni-muenster.de; Schäfers, Klaus P.; Hoerr, Verena

Purpose: The fusion of positron emission tomography (PET) and magnetic resonance imaging (MRI) data can be a challenging task in whole-body PET-MRI. The quality of the registration between these two modalities in large field-of-views (FOV) is often degraded by geometric distortions of the MRI data. The distortions at the edges of large FOVs mainly originate from MRI gradient nonlinearities. This work describes a method to measure and correct for these kind of geometric distortions in small animal MRI scanners to improve the registration accuracy of PET and MRI data. Methods: The authors have developed a geometric phantom which allows themore » measurement of geometric distortions in all spatial axes via control points. These control points are detected semiautomatically in both PET and MRI data with a subpixel accuracy. The spatial transformation between PET and MRI data is determined with these control points via 3D thin-plate splines (3D TPS). The transformation derived from the 3D TPS is finally applied to real MRI mouse data, which were acquired with the same scan parameters used in the phantom data acquisitions. Additionally, the influence of the phantom material on the homogeneity of the magnetic field is determined via field mapping. Results: The spatial shift according to the magnetic field homogeneity caused by the phantom material was determined to a mean of 0.1 mm. The results of the correction show that distortion with a maximum error of 4 mm could be reduced to less than 1 mm with the proposed correction method. Furthermore, the control point-based registration of PET and MRI data showed improved congruence after correction. Conclusions: The developed phantom has been shown to have no considerable negative effect on the homogeneity of the magnetic field. The proposed method yields an appropriate correction of the measured MRI distortion and is able to improve the PET and MRI registration. Furthermore, the method is applicable to whole-body small

Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?

PubMed Central

Tang, Catherine; Russell, Pamela J; Martiniello-Wilks, Rosetta; J Rasko, John E; Khatri, Aparajita

2010-01-01

Ineffective treatment and poor patient management continue to plague the arena of clinical oncology. The crucial issues include inadequate treatment efficacy due to ineffective targeting of cancer deposits, systemic toxicities, suboptimal cancer detection and disease monitoring. This has led to the quest for clinically relevant, innovative multifaceted solutions such as development of targeted and traceable therapies. Mesenchymal stem cells (MSCs) have the intrinsic ability to “home” to growing tumors and are hypoimmunogenic. Therefore, these can be used as (a) “Trojan Horses” to deliver gene therapy directly into the tumors and (b) carriers of nanoparticles to allow cell tracking and simultaneous cancer detection. The camouflage of MSC carriers can potentially tackle the issues of safety, vector, and/or transgene immunogenicity as well as nanoparticle clearance and toxicity. The versatility of the nanotechnology platform could allow cellular tracking using single or multimodal imaging modalities. Toward that end, noninvasive magnetic resonance imaging (MRI) is fast becoming a clinical favorite, though there is scope for improvement in its accuracy and sensitivity. In that, use of superparamagnetic iron-oxide nanoparticles (SPION) as MRI contrast enhancers may be the best option for tracking therapeutic MSC. The prospects and consequences of synergistic approaches using MSC carriers, gene therapy, and SPION in developing cancer diagnostics and therapeutics are discussed. STEM CELLS 2010; 28:1686–1702. PMID:20629172

Improved FastICA algorithm in fMRI data analysis using the sparsity property of the sources.

PubMed

Ge, Ruiyang; Wang, Yubao; Zhang, Jipeng; Yao, Li; Zhang, Hang; Long, Zhiying

2016-04-01

As a blind source separation technique, independent component analysis (ICA) has many applications in functional magnetic resonance imaging (fMRI). Although either temporal or spatial prior information has been introduced into the constrained ICA and semi-blind ICA methods to improve the performance of ICA in fMRI data analysis, certain types of additional prior information, such as the sparsity, has seldom been added to the ICA algorithms as constraints. In this study, we proposed a SparseFastICA method by adding the source sparsity as a constraint to the FastICA algorithm to improve the performance of the widely used FastICA. The source sparsity is estimated through a smoothed ℓ0 norm method. We performed experimental tests on both simulated data and real fMRI data to investigate the feasibility and robustness of SparseFastICA and made a performance comparison between SparseFastICA, FastICA and Infomax ICA. Results of the simulated and real fMRI data demonstrated the feasibility and robustness of SparseFastICA for the source separation in fMRI data. Both the simulated and real fMRI experimental results showed that SparseFastICA has better robustness to noise and better spatial detection power than FastICA. Although the spatial detection power of SparseFastICA and Infomax did not show significant difference, SparseFastICA had faster computation speed than Infomax. SparseFastICA was comparable to the Infomax algorithm with a faster computation speed. More importantly, SparseFastICA outperformed FastICA in robustness and spatial detection power and can be used to identify more accurate brain networks than FastICA algorithm. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved reactive nanoparticles to treat dentin hypersensitivity.

PubMed

Toledano-Osorio, Manuel; Osorio, Estrella; Aguilera, Fátima S; Luis Medina-Castillo, Antonio; Toledano, Manuel; Osorio, Raquel

2018-05-01

The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (δ) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus

Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application

NASA Astrophysics Data System (ADS)

Tegafaw, Tirusew; Xu, Wenlong; Wasi Ahmad, Md; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho

2015-09-01

A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd3+ (8S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy3+ (6H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd3+ and Dy3+ and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

Gadolinium-Encapsulating Iron Oxide Nanoprobe as Activatable NMR/MRI Contrast Agent

PubMed Central

Santra, Santimukul; Jativa, Samuel D.; Kaittanis, Charalambos; Normand, Guillaume; Grimm, Jan; Perez, J. Manuel

2012-01-01

Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the polyacrylic acid (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA) yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T1). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T1 relaxation rate (1/T1) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T1-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T1 signal was observed. This result suggests that upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH = 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T1 activation. No change in T1 was observed when the Gd-DTPA complex was chemically conjugated on the surface of the nanoparticle's polymeric coating or when encapsulated in the polymeric coating of a non-magnetic nanoparticle. These results confirmed that the observed (T1) quenching of the composite magnetic nanoprobe is due to the encapsulation and close proximity of the Gd ion to the nanoparticles superparamagnetic iron oxide (IO) core. In addition, when an anticancer drug (Taxol) was co-encapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T1 activation of the probe coincide with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T1 nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI. PMID:22809405

Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

NASA Astrophysics Data System (ADS)

Siddiqui, Talha S.

Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

Stability of polyelectrolyte-coated iron nanoparticles for T2-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

McGrath, Andrew J.; Dolan, Ciaran; Cheong, Soshan; Herman, David A. J.; Naysmith, Briar; Zong, Fangrong; Galvosas, Petrik; Farrand, Kathryn J.; Hermans, Ian F.; Brimble, Margaret; Williams, David E.; Jin, Jianyong; Tilley, Richard D.

2017-10-01

Iron nanoparticles are highly-effective magnetic nanoparticles for T2 magnetic resonance imaging (MRI). However, the stability of their magnetic properties is dependent on good protection of the iron core from oxidation in aqueous media. Here we report the synthesis of custom-synthesized phosphonate-grafted polyelectrolytes (PolyM3) of various chain lengths, for efficient coating of iron nanoparticles with a native iron oxide shell. The size of the nanoparticle-polyelectrolyte assemblies was investigated by transmission electron microscopy and dynamic light scattering, while surface attachment was confirmed by Fourier transform infrared spectroscopy. Low cytotoxicity was observed for each of the nanoparticle-polyelectrolyte ("Fe-PolyM3") assemblies, with good cell viability (>80%) remaining up to 100 μg mL-1 Fe in HeLa cells. When applied in T2-weighted MRI, corresponding T2 relaxivities (r2) of the Fe-PolyM3 assemblies were found to be dependent on the chain length of the polyelectrolyte. A significant increase in contrast was observed when polyelectrolyte chain length was increased from 6 to 65 repeating units, implying a critical chain length required for stabilization of the α-Fe nanoparticle core.

Ni-Fe2O4 nanoparticles as contrast agents for magnetic resonance imaging.

PubMed

Ahmad, Tanveer; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun

2011-07-01

Reported herein is the synthesis of a dextran coating on nickel ferrite (Ni-Fe2O4) nanoparticles via chemical coprecipitation. The aqueous solution of the synthesized nanoparticles showed good colloidal stability, and no precipitate was observed 20 months after the synthesis. The coated nanoparticles were found to be cylindrical in shape in the TEM images, and showed a uniform size distribution with an average length and diameter of 17 and 4 nm, respectively. The coated particles were evaluated as potential T1 and T2 contrast agents for MRI. The T1 and T2 relaxations of the hydrogen protons in the water molecules in an aqueous solution of dextran-coated Ni-Fe2O4 nanoparticles were studied. It was found that the T1 relaxivity for the aqueous solution of dextran-coated nanoparticles was slightly greater than that of a commercial Gd-DTPA-BMA contrast agent. The T2 relaxivity, however, was almost twice that of the commercial Gd-DTPA-BMA contrast agent. Animal experimentation also demonstrated that the dextran-coated Ni-Fe2O4 nanoparticles are suitable for use as either T1 or T2 contrast agents in MRI.

Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle targeting.

PubMed

Fernandes, B; Silva, R; Ribeiro, A; Matamá, T; Gomes, A C; Cavaco-Paulo, A M

2015-06-01

Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery. Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively. Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts. The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release

Feasibility of shutter-speed DCE-MRI for improved prostate cancer detection.

PubMed

Li, Xin; Priest, Ryan A; Woodward, William J; Tagge, Ian J; Siddiqui, Faisal; Huang, Wei; Rooney, William D; Beer, Tomasz M; Garzotto, Mark G; Springer, Charles S

2013-01-01

The feasibility of shutter-speed model dynamic-contrast-enhanced MRI pharmacokinetic analyses for prostate cancer detection was investigated in a prebiopsy patient cohort. Differences of results from the fast-exchange-regime-allowed (FXR-a) shutter-speed model version and the fast-exchange-limit-constrained (FXL-c) standard model are demonstrated. Although the spatial information is more limited, postdynamic-contrast-enhanced MRI biopsy specimens were also examined. The MRI results were correlated with the biopsy pathology findings. Of all the model parameters, region-of-interest-averaged K(trans) difference [ΔK(trans) ≡ K(trans)(FXR-a) - K(trans)(FXL-c)] or two-dimensional K(trans)(FXR-a) vs. k(ep)(FXR-a) values were found to provide the most useful biomarkers for malignant/benign prostate tissue discrimination (at 100% sensitivity for a population of 13, the specificity is 88%) and disease burden determination. (The best specificity for the fast-exchange-limit-constrained analysis is 63%, with the two-dimensional plot.) K(trans) and k(ep) are each measures of passive transcapillary contrast reagent transfer rate constants. Parameter value increases with shutter-speed model (relative to standard model) analysis are larger in malignant foci than in normal-appearing glandular tissue. Pathology analyses verify the shutter-speed model (FXR-a) promise for prostate cancer detection. Parametric mapping may further improve pharmacokinetic biomarker performance. Copyright © 2012 Wiley Periodicals, Inc.

Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

PubMed

Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

2015-01-01

Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery.

Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

PubMed Central

Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

2015-01-01

Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

Unwrapping eddy current compensation: improved compensation of eddy current induced baseline shifts in high-resolution phase-contrast MRI at 9.4 Tesla.

PubMed

Espe, Emil K S; Zhang, Lili; Sjaastad, Ivar

2014-10-01

Phase-contrast MRI (PC-MRI) is a versatile tool allowing evaluation of in vivo motion, but is sensitive to eddy current induced phase offsets, causing errors in the measured velocities. In high-resolution PC-MRI, these offsets can be sufficiently large to cause wrapping in the baseline phase, rendering conventional eddy current compensation (ECC) inadequate. The purpose of this study was to develop an improved ECC technique (unwrapping ECC) able to handle baseline phase discontinuities. Baseline phase discontinuities are unwrapped by minimizing the spatiotemporal standard deviation of the static-tissue phase. Computer simulations were used for demonstrating the theoretical foundation of the proposed technique. The presence of baseline wrapping was confirmed in high-resolution myocardial PC-MRI of a normal rat heart at 9.4 Tesla (T), and the performance of unwrapping ECC was compared with conventional ECC. Areas of phase wrapping in static regions were clearly evident in high-resolution PC-MRI. The proposed technique successfully eliminated discontinuities in the baseline, and resulted in significantly better ECC than the conventional approach. We report the occurrence of baseline phase wrapping in PC-MRI, and provide an improved ECC technique capable of handling its presence. Unwrapping ECC offers improved correction of eddy current induced baseline shifts in high-resolution PC-MRI. Copyright © 2013 Wiley Periodicals, Inc.

Incorporation of MRI-AIF Information For Improved Kinetic Modelling of Dynamic PET Data

NASA Astrophysics Data System (ADS)

Sari, Hasan; Erlandsson, Kjell; Thielemans, Kris; Atkinson, David; Ourselin, Sebastien; Arridge, Simon; Hutton, Brian F.

2015-06-01

In the analysis of dynamic PET data, compartmental kinetic analysis methods require an accurate knowledge of the arterial input function (AIF). Although arterial blood sampling is the gold standard of the methods used to measure the AIF, it is usually not preferred as it is an invasive method. An alternative method is the simultaneous estimation method (SIME), where physiological parameters and the AIF are estimated together, using information from different anatomical regions. Due to the large number of parameters to estimate in its optimisation, SIME is a computationally complex method and may sometimes fail to give accurate estimates. In this work, we try to improve SIME by utilising an input function derived from a simultaneously obtained DSC-MRI scan. With the assumption that the true value of one of the six parameter PET-AIF model can be derived from an MRI-AIF, the method is tested using simulated data. The results indicate that SIME can yield more robust results when the MRI information is included with a significant reduction in absolute bias of Ki estimates.

Gold Nanoparticles: Promising Agent to Improve the Diagnosis and Therapy of Cancer.

PubMed

Ning, Limin; Zhu, Benwei; Gao, Tao

2017-01-01

Gold nanoparticles have been exploited for nanobiotechnology applications for the last two decades. New insights of the nanomaterials as promising agent for cancer diagnosis and therapy have just started to emerge. Due to the size- and shape-dependent optical, electrical and thermal properties, gold nanoparticles are being developed as diagnostic reagents, drug carriers, contrast agents, photothermal agents and radiosensitisers. This review aims to summarize the latest advances of gold nanoparticles in cancer treatment. We undertook a systematical search for research literatures using a well-framed review question and presented the applications in different fields, including early cancer diagnosis, imaging, radiotherapy, chemotherapy, gene therapy and photothermal therapy, which were fully described, filtered, combined and analyzed in order to provide documented proofs on the applications of gold nanoparticles in current cancer treatments. One hundred and sixty papers were included in the review, the majority of which represent latest researches in the field of gold nanoparticle-based diagnosis and therapy for cancer. Conventional treatment strategies for cancer cannot identify normal and cancer cells. While due to the high surface area to volume ratio and rich surface functionalization chemistry, gold nanoparticle can greatly enhance the targeting with adverse side effects of traditional treatment on normal tissues being avoided. Gold nanoparticles have greatly improved the traditional treatment due to their unique properties. However, their size-dependent toxicity, distribution and clearance need further studies to make them a clinical reality. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pirfenidone Nanoparticles Improve Corneal Wound Healing and Prevent Scarring Following Alkali Burn

PubMed Central

Chowdhury, Sushovan; Guha, Rajdeep; Trivedi, Ruchit; Kompella, Uday B.; Konar, Aditya; Hazra, Sarbani

2013-01-01

Purpose To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn. Methods Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA) synthesis by TGFβ induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared, characterized and their cellular entry was examined in primary corneal fibroblast cells by fluorescence microscopy. Alkali burn was induced in one eye of Sprague Dawley rats followed by daily topical treatment with free pirfenidone, pirfenidone nanoparticles or vehicle. Corneal re-epithelialization was assessed daily by flourescein dye test; absence of stained area indicated complete re-epithelialization and the time for complete re-epithelialization was determined. Corneal haze was assessed daily for 7 days under slit lamp microscope and graded using a standard method. After 7 days, collagen I deposition in the superficial layer of cornea was examined by immunohistochemistry. Results Pirfenidone prevented (P<0.05) increase in TGF β induced collagen I and α-SMA synthesis by corneal fibroblasts in a dose dependent manner. Pirfenidone could be loaded successfully within PLGA nanoparticles, which entered the corneal fibroblasts within 5 minutes. Pirfenidone nanoparticles but not free pirfenidone significantly (P<0.05) reduced collagen I level, corneal haze and the time for corneal re-epithelialization following alkali burn. Conclusion Pirfenidone decreases collagen synthesis and prevents myofibroblast formation. Pirfenidone nanoparticles improve corneal wound healing and prevent fibrosis. Pirfenidone nanoparticles are of potential value in treating corneal chemical burns and other corneal fibrotic diseases. PMID:23940587

Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity.

PubMed

Perche, F; Yi, Y; Hespel, L; Mi, P; Dirisala, A; Cabral, H; Miyata, K; Kataoka, K

2016-06-01

Current technology of siRNA delivery relies on pharmaceutical dosage forms to route maximal doses of siRNA to the tumor. However, this rationale does not address intracellular bottlenecks governing silencing activity. Here, we tested the impact of hydroxychloroquine conjugation on the intracellular fate and silencing activity of siRNA conjugated PEGylated gold nanoparticles. Addition of hydroxychloroquine improved endosomal escape and increased siRNA guide strand distribution to the RNA induced silencing complex (RISC), both crucial obstacles to the potency of siRNA. This modification significantly improved gene downregulation in cellulo. Altogether, our data suggest the benefit of this modification for the design of improved siRNA delivery systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

MRI-Based Nonrigid Motion Correction in Simultaneous PET/MRI

PubMed Central

Chun, Se Young; Reese, Timothy G.; Ouyang, Jinsong; Guerin, Bastien; Catana, Ciprian; Zhu, Xuping; Alpert, Nathaniel M.; El Fakhri, Georges

2014-01-01

Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise. This paper presents an approach to respiratory motion correction using simultaneous PET/MRI to demonstrate initial results in phantoms, rabbits, and nonhuman primates and discusses the prospects for clinical application. Methods Studies with a deformable phantom, a free-breathing primate, and rabbits implanted with radioactive beads were performed with simultaneous PET/MRI. Motion fields were estimated from concurrently acquired tagged MR images using 2 B-spline nonrigid image registration methods and incorporated into a PET list-mode ordered-subsets expectation maximization algorithm. Using the measured motion fields to transform both the emission data and the attenuation data, we could use all the coincidence data to reconstruct any phase of the respiratory cycle. We compared the resulting SNR and the channelized Hotelling observer (CHO) detection signal-to-noise ratio (SNR) in the motion-corrected reconstruction with the results obtained from standard gating and uncorrected studies. Results Motion correction virtually eliminated motion blur without reducing SNR, yielding images with SNR comparable to those obtained by gating with 5–8 times longer acquisitions in all studies. The CHO study in dynamic phantoms demonstrated a significant improvement (166%–276%) in lesion detection SNR with MRI-based motion correction as compared with gating (P < 0.001). This improvement was 43%–92% for large motion compared with lesion detection without motion correction (P < 0.001). CHO SNR in the rabbit studies confirmed these results. Conclusion Tagged MRI motion correction in simultaneous PET/MRI significantly improves lesion detection

Multimodal Superparamagnetic Nanoparticles with Unusually Enhanced Specific Absorption Rate for Synergetic Cancer Therapeutics and Magnetic Resonance Imaging.

PubMed

Thorat, Nanasaheb D; Bohara, Raghvendra A; Malgras, Victor; Tofail, Syed A M; Ahamad, Tansir; Alshehri, Saad M; Wu, Kevin C-W; Yamauchi, Yusuke

2016-06-15

Superparamagnetic nanoparticles (SPMNPs) used for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) cancer therapy frequently face trade off between a high magnetization saturation and their good colloidal stability, high specific absorption rate (SAR), and most importantly biological compatibility. This necessitates the development of new nanomaterials, as MFH and MRI are considered to be one of the most promising combined noninvasive treatments. In the present study, we investigated polyethylene glycol (PEG) functionalized La1-xSrxMnO3 (LSMO) SPMNPs for efficient cancer hyperthermia therapy and MRI application. The superparamagnetic nanomaterial revealed excellent colloidal stability and biocompatibility. A high SAR of 390 W/g was observed due to higher colloidal stability leading to an increased Brownian and Neel's spin relaxation. Cell viability of PEG capped nanoparticles is up to 80% on different cell lines tested rigorously using different methods. PEG coating provided excellent hemocompatibility to human red blood cells as PEG functionalized SPMNPs reduced hemolysis efficiently compared to its uncoated counterpart. Magnetic fluid hyperthermia of SPMNPs resulted in cancer cell death up to 80%. Additionally, improved MRI characteristics were also observed for the PEG capped La1-xSrxMnO3 formulation in aqueous medium compared to the bare LSMO. Taken together, PEG capped SPMNPs can be useful for diagnosis, efficient magnetic fluid hyperthermia, and multimodal cancer treatment as the amphiphilicity of PEG can easily be utilized to encapsulate hydrophobic drugs.

Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

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

Park, Ji-Ae, E-mail: jpark@kirams.re.kr; Lee, Yong Jin; Ko, In Ok

2014-12-12

Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyKmore » peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.« less

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics.

PubMed

Wei, Yinghui; Luo, Xiaoting; Guan, Jiani; Ma, Jianping; Zhong, Yicong; Luo, Jingwen; Li, Fanzhu

2017-11-01

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC kidney /AUC plasma  = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment.

PubMed

Song, Yu; Cai, Han; Yin, Tingjie; Huo, Meirong; Ma, Ping; Zhou, Jianping; Lai, Wenfang

2018-01-01

Lung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment. The redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model. This HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 μg mL -1 . Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol ® , PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles

Towards hybrid biocompatible magnetic rHuman serum albumin-based nanoparticles: use of ultra-small (CeLn)3/4+ cation-doped maghemite nanoparticles as functional shell

NASA Astrophysics Data System (ADS)

Israel, Liron L.; Kovalenko, Elena I.; Boyko, Anna A.; Sapozhnikov, Alexander M.; Rosenberger, Ina; Kreuter, Jörg; Passoni, Lorena; Lellouche, Jean-Paul

2015-01-01

Human serum albumin (HSA) is a protein found in human blood. Over the last decade, HSA has been evaluated as a promising drug carrier. However, not being magnetic, HSA cannot be used for biomedical applications such as magnetic resonance imaging (MRI) and magnetic drug targeting. Therefore, subsequent composites building on iron oxide nanoparticles that are already used clinically as MRI contrast agents are extensively studied. Recently and in this context, innovative fully hydrophilic ultra-small CAN-stabilized maghemite ((CeLn)3/4+-γ-Fe2O3) nanoparticles have been readily fabricated. The present study discusses the design, fabrication, and characterization of a dual phase hybrid core (rHSA)-shell ((CeLn)3/4+-γ-Fe2O3 NPs) nanosystem. Quite importantly and in contrast to widely used encapsulation strategies, rHSA NP surface-attached (CeLn)3/4+-γ-Fe2O3 NPs enabled to exploit both rHSA (protein functionalities) and (CeLn)3/4+-γ-Fe2O3 NP surface functionalities (COOH and ligand L coordinative exchange) in addition to very effective MRI contrast capability due to optimal accessibility of H2O molecules with the outer magnetic phase. Resulting hybrid nanoparticles might be used as a platform modular system for therapeutic (drug delivery system) and MR diagnostic purposes.

Experimental Evaluation of Oxide Nanoparticles as Friction and Wear Improvement Additives in Motor Oil

DOE PAGES

Demas, Nicholaos G.; Erck, Robert A.; Lorenzo-Martin, Cinta; ...

2017-01-30

The effect of two nanoparticle oxides on friction and wear was studied under laboratory test conditions using a reciprocating test machine and two test configurations. The addition of these nanoparticles in base stock oil under certain conditions reduced the coefficient of friction and improved wear, but that depended on the test configuration. Examination of the rubbed surfaces showed the pronounced formation of a tribofilm in some cases, while polishing on the surface was also observed in other cases. Contact configuration is important when oxide nanoparticles are being evaluated and the conclusions about their efficacy can be vastly different.

Lipid nanoparticle interactions and assemblies

NASA Astrophysics Data System (ADS)

Preiss, Matthew Ryan

Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron

CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles

PubMed Central

Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

2016-01-01

Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis. PMID:27162559

Effect of Milling Time on the Blocking Temperature of Nanoparticles of Magnetocaloric Gd5Si4

NASA Astrophysics Data System (ADS)

Hadimani, Ravi; Gupta, Shalbh; Harstad, Shane; Pecharsky, Vitalij; Jiles, David; David C Jiles Team; Vitalij Pecharsky Collaboration

Extensive research has been done on giant magnetocaloric material Gd5(SixGe1-x)4 to improve adiabatic temperature/isothermal entropy change. However, there have been only a few reports on fabrication of nanostructure/nanoparticles that can be used to tune various properties by changing the length scale. Recently we have reported fabrication of room temperature ferromagnetic nanoparticles of Gd5Si4 using high energy ball milling. These nanoparticles have potential applications in biomedical engineering such as better T2 MRI contrast agents and in hypothermia. Here we report the effect of milling time on the blocking temperature, micro-structure, crystal structure, and magnetic properties of these nanoparticles. Magnetization vs. temperature at an applied field of 100 Oe is measured for all the ball milled samples. Bulk Gd5Si4 has a transition temperature of ~340 K. There are two phase transitions observed in the nanoparticles, one near 300 K corresponding to the Gd5Si4 phase and another between 75-150 K corresponding to Gd5Si3. Zero Field Cooling (ZFC) and Field Cooling (FC) were measured. The blocking temperatures for the nanoparticles increase with decrease in milling time.

Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells

NASA Astrophysics Data System (ADS)

Schwarz, Sebastian; Fernandes, Fabiana; Sanroman, Laura; Hodenius, Michael; Lang, Claus; Himmelreich, Uwe; Schmitz-Rode, Thomas; Schueler, Dirk; Hoehn, Mathias; Zenke, Martin; Hieronymus, Thomas

2009-05-01

Accurate delivery of cells to target organs is critical for success of cell-based therapies with stem cells or immune cells such as antigen-presenting dendritic cells (DC). Labeling with contrast agents before implantation provides a powerful means for monitoring cellular migration using magnetic resonance imaging (MRI). In this study, we investigated the uptake of fully synthesized or bacterial magnetic nanoparticles (MNPs) into hematopoietic Flt3 + stem cells and DC from mouse bone marrow. We show that (i) uptake of both synthetic and biogenic nanoparticles into cells endow magnetic activity and (ii) low numbers of MNP-loaded cells are readily detected by MRI.

Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging.

PubMed

Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G

2015-08-19

Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early stage cancer diagnosis. Gadolinium (Gd)(III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high X-ray attenuation coefficient, is an ideal contrast agent candidate for X-ray-based CT imaging. Gd metal-organic framework (MOF) nanoparticles with tunable size, high Gd(III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multimodal imaging probes.

Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging

PubMed Central

Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G.

2015-01-01

Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes. PMID:26147906

Improve definition of titanium tandems in MR-guided high dose rate brachytherapy for cervical cancer using proton density weighted MRI

PubMed Central

2013-01-01

Background For cervical cancer patients treated with MR-guided high dose rate brachytherapy, the accuracy of radiation delivery depends on accurate localization of both tumors and the applicator, e.g. tandem and ovoid. Standard T2-weighted (T2W) MRI has good tumor-tissue contrast. However, it suffers from poor uterus-tandem contrast, which makes the tandem delineation very challenging. In this study, we evaluated the possibility of using proton density weighted (PDW) MRI to improve the definition of titanium tandems. Methods Both T2W and PDW MRI images were obtained from each cervical cancer patient. Imaging parameters were kept the same between the T2W and PDW sequences for each patient except the echo time (90 ms for T2W and 5.5 ms for PDW) and the slice thickness (0.5 cm for T2W and 0.25 cm for PDW). Uterus-tandem contrast was calculated by the equation C = (Su-St)/Su, where Su and St represented the average signal in the uterus and the tandem, respectively. The diameter of the tandem was measured 1.5 cm away from the tip of the tandem. The tandem was segmented by the histogram thresholding technique. Results PDW MRI could significantly improve the uterus-tandem contrast compared to T2W MRI (0.42±0.24 for T2W MRI, 0.77±0.14 for PDW MRI, p=0.0002). The average difference between the measured and physical diameters of the tandem was reduced from 0.20±0.15 cm by using T2W MRI to 0.10±0.11 cm by using PDW MRI (p=0.0003). The tandem segmented from the PDW image looked more uniform and complete compared to that from the T2W image. Conclusions Compared to the standard T2W MRI, PDW MRI has better uterus-tandem contrast. The information provided by PDW MRI is complementary to those provided by T2W MRI. Therefore, we recommend adding PDW MRI to the simulation protocol to assist tandem delineation process for cervical cancer patients. PMID:23327682

Magnetic Nanoparticles in Cancer Theranostics

PubMed Central

Gobbo, Oliviero L.; Sjaastad, Kristine; Radomski, Marek W.; Volkov, Yuri; Prina-Mello, Adriele

2015-01-01

In a report from 2008, The International Agency for Research on Cancer predicted a tripled cancer incidence from 1975, projecting a possible 13-17 million cancer deaths worldwide by 2030. While new treatments are evolving and reaching approval for different cancer types, the main prevention of cancer mortality is through early diagnosis, detection and treatment of malignant cell growth. The last decades have seen a development of new imaging techniques now in widespread clinical use. The development of nano-imaging through fluorescent imaging and magnetic resonance imaging (MRI) has the potential to detect and diagnose cancer at an earlier stage than with current imaging methods. The characteristic properties of nanoparticles result in their theranostic potential allowing for simultaneous detection of and treatment of the disease. This review provides state of the art of the nanotechnological applications for cancer therapy. Furthermore, it advances a novel concept of personalized nanomedical theranostic therapy using iron oxide magnetic nanoparticles in conjunction with MRI imaging. Regulatory and industrial perspectives are also included to outline future perspectives in nanotechnological cancer research. PMID:26379790

Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging.

PubMed

Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Hübner, Frank; Waidmann, Oliver; Zeuzem, Stefan; Korf, Horst-Werner; Terfort, Andreas; Gelperina, Svetlana; Vogl, Thomas J; Kreuter, Jörg; Piiper, Albrecht

2015-02-10

Nanoparticle (NP)-based contrast agents that enable high resolution anatomic T1-weighted magnetic resonance imaging (MRI) offer the prospect of improving differential diagnosis of liver tumors such as hepatocellular carcinoma (HCC). In the present study, we investigated the possibility of employing novel non-toxic human serum albumin nanoparticles conjugated with Gd-DTPA and rhodamine 123 (Gd-Rho-HSA-NPs) for the detection of HCC by T1-weighted MRI. In addition, the influence of surface coating of the NPs with poloxamine 908, which alters the absorptive behavior of NPs and changes their distribution between the liver and tumor was examined. MRI of transgenic mice with endogenously formed HCCs following intravenous injection of Gd-Rho-HSA-NPs revealed a strong negative contrast of the tumors. Contrasting of the HCCs by NP-enhanced MRI required less Gd as compared to gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced MRI, which currently provides the most sensitive detection of HCC in patients. Immunohistochemical analyses revealed that the Gd-Rho-HSA-NPs were localized to macrophages, which were - similar to HCC in patients - fewer in number in HCC as compared to the liver tissue, which is in agreement with the negative contrasting of HCC in Gd-Rho-HSA-NP-enhanced MRI. Poloxamine-coated NPs showed lower accumulation in the tumor macrophages and caused a longer lasting enhancement of the MRI signal. These data indicate that Gd-Rho-HSA-NPs enable sensitive detection of HCC by T1-weighted MRI in mice with endogenous HCC through their uptake by macrophages. Poloxamine coating of the NPs delayed the tumor localization of the NPs. Copyright © 2014 Elsevier B.V. All rights reserved.

Mesenchymal stromal cell labeling by new uncoated superparamagnetic maghemite nanoparticles in comparison with commercial Resovist--an initial in vitro study.

PubMed

Skopalik, Josef; Polakova, Katerina; Havrdova, Marketa; Justan, Ivan; Magro, Massimiliano; Milde, David; Knopfova, Lucia; Smarda, Jan; Polakova, Helena; Gabrielova, Eva; Vianello, Fabio; Michalek, Jaroslav; Zboril, Radek

2014-01-01

Cell therapies have emerged as a promising approach in medicine. The basis of each therapy is the injection of 1-100×10(6) cells with regenerative potential into some part of the body. Mesenchymal stromal cells (MSCs) are the most used cell type in the cell therapy nowadays, but no gold standard for the labeling of the MSCs for magnetic resonance imaging (MRI) is available yet. This work evaluates our newly synthesized uncoated superparamagnetic maghemite nanoparticles (surface-active maghemite nanoparticles - SAMNs) as an MRI contrast intracellular probe usable in a clinical 1.5 T MRI system. MSCs from rat and human donors were isolated, and then incubated at different concentrations (10-200 μg/mL) of SAMN maghemite nanoparticles for 48 hours. Viability, proliferation, and nanoparticle uptake efficiency were tested (using fluorescence microscopy, xCELLigence analysis, atomic absorption spectroscopy, and advanced microscopy techniques). Migration capacity, cluster of differentiation markers, effect of nanoparticles on long-term viability, contrast properties in MRI, and cocultivation of labeled cells with myocytes were also studied. SAMNs do not affect MSC viability if the concentration does not exceed 100 μg ferumoxide/mL, and this concentration does not alter their cell phenotype and long-term proliferation profile. After 48 hours of incubation, MSCs labeled with SAMNs show more than double the amount of iron per cell compared to Resovist-labeled cells, which correlates well with the better contrast properties of the SAMN cell sample in T2-weighted MRI. SAMN-labeled MSCs display strong adherence and excellent elasticity in a beating myocyte culture for a minimum of 7 days. Detailed in vitro tests and phantom tests on ex vivo tissue show that the new SAMNs are efficient MRI contrast agent probes with exclusive intracellular uptake and high biological safety.

X-space MPI: magnetic nanoparticles for safe medical imaging.

PubMed

Goodwill, Patrick William; Saritas, Emine Ulku; Croft, Laura Rose; Kim, Tyson N; Krishnan, Kannan M; Schaffer, David V; Conolly, Steven M

2012-07-24

One quarter of all iodinated contrast X-ray clinical imaging studies are now performed on Chronic Kidney Disease (CKD) patients. Unfortunately, the iodine contrast agent used in X-ray is often toxic to CKD patients' weak kidneys, leading to significant morbidity and mortality. Hence, we are pioneering a new medical imaging method, called Magnetic Particle Imaging (MPI), to replace X-ray and CT iodinated angiography, especially for CKD patients. MPI uses magnetic nanoparticle contrast agents that are much safer than iodine for CKD patients. MPI already offers superb contrast and extraordinary sensitivity. The iron oxide nanoparticle tracers required for MPI are also used in MRI, and some are already approved for human use, but the contrast agents are far more effective at illuminating blood vessels when used in the MPI modality. We have recently developed a systems theoretic framework for MPI called x-space MPI, which has already dramatically improved the speed and robustness of MPI image reconstruction. X-space MPI has allowed us to optimize the hardware for fi ve MPI scanners. Moreover, x-space MPI provides a powerful framework for optimizing the size and magnetic properties of the iron oxide nanoparticle tracers used in MPI. Currently MPI nanoparticles have diameters in the 10-20 nanometer range, enabling millimeter-scale resolution in small animals. X-space MPI theory predicts that larger nanoparticles could enable up to 250 micrometer resolution imaging, which would represent a major breakthrough in safe imaging for CKD patients.

Efficient MRI labeling of endothelial progenitor cells: design of thiolated surface stabilized superparamagnetic iron oxide nanoparticles.

PubMed

Shahnaz, Gul; Kremser, Christian; Reinisch, Andreas; Vetter, Anja; Laffleur, Flavia; Rahmat, Deni; Iqbal, Javed; Dünnhaupt, Sarah; Salvenmoser, Willi; Tessadri, Richard; Griesser, Ulrich; Bernkop-Schnürch, Andreas

2013-11-01

The aim of this study was to design thiolated surface stabilized superparamagnetic iron oxide nanoparticles (TSS-SPIONs) for efficient internalization with high MRI sensitivity. TSS-SPIONs were developed by chelation between thiolated chitosan-thioglycolic acid (chitosan-TGA) hydrogel and iron ions (Fe(2+)/Fe(3+)). Likely, unmodified chitosan hydrogel SPIONs (UC-SPIONs) and uncoated SPIONs were used as control. Moreover, TSS-SPIONs were investigated regarding to their iron core size, hydrodynamic diameter, zeta potential, iron contents, molar relaxivities (r1 and r2), and cellular internalization. TSS-SPIONs demonstrated an iron oxide core diameter (crystallite size by XRD) of 3.1 ± 0.02 nm, a hydrodynamic diameter of 94 ± 20 nm, a zeta potential of +21 ± 5 mV, and an iron content of 3.6 ± 0.9 mg/mL. In addition, internalization of TSS-SPIONs into human endothelial progenitor cells (EPC) from umbilical cord blood was more than threefold and 17-fold higher in contrast to UC-SPIONs and SPIONs, respectively. With twofold lower incubation iron concentration of TSS-SPIONs, more than threefold higher internalization was achieved as compared to Resovist®. Also, cell viability of more than 90% was observed in the presence of TSS-SPIONs after 24h. The molar MR relaxivities (r2) value at 1.5 T was threefold higher than that of Resovist® and demonstrated that TSS-SPIONs have the potential as very effective T2 contrast-enhancement agent. According to these findings, TSS-SPIONs with efficient internalization, lower cytotoxicity, and high MRI sensitivity seem to be promising for cell tracking. Copyright © 2013 Elsevier B.V. All rights reserved.

Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects

NASA Astrophysics Data System (ADS)

Nejadnik, Hossein; Lenkov, Olga; Gassert, Florian; Fretwell, Deborah; Lam, Isaac; Daldrup-Link, Heike E.

2016-05-01

Human mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.

Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects.

PubMed

Nejadnik, Hossein; Lenkov, Olga; Gassert, Florian; Fretwell, Deborah; Lam, Isaac; Daldrup-Link, Heike E

2016-05-13

Human mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.

New Perspectives on Biomedical Applications of Iron Oxide Nanoparticles.

PubMed

Magro, Massimiliano; Baratella, Davide; Bonaiuto, Emanuela; de A Roger, Jessica; Vianello, Fabio

2018-02-12

Iron oxide nanomaterials are considered promising tools for improved therapeutic efficacy and diagnostic applications in biomedicine. Accordingly, engineered iron oxide nanomaterials are increasingly proposed in biomedicine, and the interdisciplinary researches involving physics, chemistry, biology (nanotechnology) and medicine have led to exciting developments in the last decades. The progresses of the development of magnetic nanoparticles with tailored physico-chemical and surface properties produced a variety of clinically relevant applications, spanning from magnetic resonance imaging (MRI), drug delivery, magnetic hyperthermia, to in vitro diagnostics. Notwithstanding the wellknown conventional synthetic procedures and their wide use, along with recent advances in the synthetic methods open the door to new generations of naked iron oxide nanoparticles possessing peculiar surface chemistries, suitable for other competitive biomedical applications. New abilities to rationally manipulate iron oxides and their physical, chemical, and biological properties, allow the emersion of additional possibilities for designing novel nanomaterials for theranostic applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION-cmHsp70.1)

NASA Astrophysics Data System (ADS)

Shevtsov, Maxim A.; Nikolaev, Boris P.; Ryzhov, Vyacheslav A.; Yakovleva, Ludmila Y.; Marchenko, Yaroslav Y.; Parr, Marina A.; Rolich, Valerij I.; Mikhrina, Anastasiya L.; Dobrodumov, Anatolii V.; Pitkin, Emil; Multhoff, Gabriele

2015-12-01

The stress-inducible 72 kDa heat shock protein Hsp70 is known to be expressed on the membrane of highly aggressive tumor cells including high-grade gliomas, but not on the corresponding normal cells. Membrane Hsp70 (mHsp70) is rapidly internalized into tumor cells and thus targeting of mHsp70 might provide a promising strategy for theranostics. Superparamagnetic iron oxide nanoparticles (SPIONs) are contrast negative agents that are used for the detection of tumors with MRI. Herein, we conjugated the Hsp70-specific antibody (cmHsp70.1) which is known to recognize mHsp70 to superparamagnetic iron nanoparticles to assess tumor-specific targeting before and after ionizing irradiation. In vitro experiments demonstrated the selectivity of SPION-cmHsp70.1 conjugates to free and mHsp70 in different tumor cell types (C6 glioblastoma, K562 leukemia, HeLa cervix carcinoma) in a dose-dependent manner. High-resolution MRI (11 T) on T2-weighted images showed the retention of the conjugates in the C6 glioma model. Accumulation of SPION-cmHsp70.1 nanoparticles in the glioma resulted in a nearly 2-fold drop of values in comparison to non-conjugated SPIONs. Biodistribution analysis using NLR-M2 measurements showed a 7-fold increase in the tumor-to-background (normal brain) uptake ratio of SPION-cmHsp70.1 conjugates in glioma-bearing rats in comparison to SPIONs. This accumulation within Hsp70-positive glioma was further enhanced after a single dose (10 Gy) of ionizing radiation. Elevated accumulation of the magnetic conjugates in the tumor due to radiosensitization proves the combination of radiotherapy and application of Hsp70-targeted agents in brain tumors.The stress-inducible 72 kDa heat shock protein Hsp70 is known to be expressed on the membrane of highly aggressive tumor cells including high-grade gliomas, but not on the corresponding normal cells. Membrane Hsp70 (mHsp70) is rapidly internalized into tumor cells and thus targeting of mHsp70 might provide a promising strategy

Curcumin conjugated silica nanoparticles for improving bioavailability and its anticancer applications.

PubMed

Gangwar, Rajesh K; Tomar, Geetanjali B; Dhumale, Vinayak A; Zinjarde, Smita; Sharma, Rishi B; Datar, Suwarna

2013-10-09

Curcumin, a yellow bioactive component of Indian spice turmeric, is known to have a wide spectrum of biological applications. In spite of various astounding therapeutic properties, it lacks in bioavailability mainly due to its poor solubility in water. In this work, we have conjugated curcumin with silica nanoparticles to improve its aqueous solubility and hence to make it more bioavailable. Conjugation and loading of curcumin with silica nanoparticles was further examined with transmission electron microscope (TEM) and thermogravimetric analyzer. Cytotoxicity analysis of synthesized silica:curcumin conjugate was studied against HeLa cell lines as well as normal fibroblast cell lines. This study shows that silica:curcumin conjugate has great potential for anticancer application.

pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

PubMed

Wang, Xue-Qing; Zhang, Qiang

2012-10-01

pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Calcium-dependent molecular fMRI using a magnetic nanosensor.

PubMed

Okada, Satoshi; Bartelle, Benjamin B; Li, Nan; Breton-Provencher, Vincent; Lee, Jiyoung J; Rodriguez, Elisenda; Melican, James; Sur, Mriganka; Jasanoff, Alan

2018-06-01

Calcium ions are ubiquitous signalling molecules in all multicellular organisms, where they mediate diverse aspects of intracellular and extracellular communication over widely varying temporal and spatial scales 1 . Though techniques to map calcium-related activity at a high resolution by optical means are well established, there is currently no reliable method to measure calcium dynamics over large volumes in intact tissue 2 . Here, we address this need by introducing a family of magnetic calcium-responsive nanoparticles (MaCaReNas) that can be detected by magnetic resonance imaging (MRI). MaCaReNas respond within seconds to [Ca 2+ ] changes in the 0.1-1.0 mM range, suitable for monitoring extracellular calcium signalling processes in the brain. We show that the probes permit the repeated detection of brain activation in response to diverse stimuli in vivo. MaCaReNas thus provide a tool for calcium-activity mapping in deep tissue and offer a precedent for the development of further nanoparticle-based sensors for dynamic molecular imaging with MRI.

Calcium-dependent molecular fMRI using a magnetic nanosensor

NASA Astrophysics Data System (ADS)

Okada, Satoshi; Bartelle, Benjamin B.; Li, Nan; Breton-Provencher, Vincent; Lee, Jiyoung J.; Rodriguez, Elisenda; Melican, James; Sur, Mriganka; Jasanoff, Alan

2018-06-01

Calcium ions are ubiquitous signalling molecules in all multicellular organisms, where they mediate diverse aspects of intracellular and extracellular communication over widely varying temporal and spatial scales1. Though techniques to map calcium-related activity at a high resolution by optical means are well established, there is currently no reliable method to measure calcium dynamics over large volumes in intact tissue2. Here, we address this need by introducing a family of magnetic calcium-responsive nanoparticles (MaCaReNas) that can be detected by magnetic resonance imaging (MRI). MaCaReNas respond within seconds to [Ca2+] changes in the 0.1-1.0 mM range, suitable for monitoring extracellular calcium signalling processes in the brain. We show that the probes permit the repeated detection of brain activation in response to diverse stimuli in vivo. MaCaReNas thus provide a tool for calcium-activity mapping in deep tissue and offer a precedent for the development of further nanoparticle-based sensors for dynamic molecular imaging with MRI.

Is MRI-based CFD able to improve clinical treatment of coarctations of aorta?

PubMed

Goubergrits, L; Riesenkampff, E; Yevtushenko, P; Schaller, J; Kertzscher, U; Berger, F; Kuehne, T

2015-01-01

Pressure drop associated with coarctation of the aorta (CoA) can be successfully treated surgically or by stent placement. However, a decreased life expectancy associated with altered aortic hemodynamics was found in long-term studies. Image-based computational fluid dynamics (CFD) is intended to support particular diagnoses, to help in choosing between treatment options, and to improve performance of treatment procedures. This study aimed to prove the ability of CFD to improve aortic hemodynamics in CoA patients. In 13 patients (6 males, 7 females; mean age 25 ± 14 years), we compared pre- and post-treatment peak systole hemodynamics [pressure drops and wall shear stress (WSS)] vs. virtual treatment as proposed by biomedical engineers. Anatomy and flow data for CFD were based on MRI and angiography. Segmentation, geometry reconstruction and virtual treatment geometry were performed using the software ZIBAmira, whereas peak systole flow conditions were simulated with the software ANSYS(®) Fluent(®). Virtual treatment significantly reduced pressure drop compared to post-treatment values by a mean of 2.8 ± 3.15 mmHg, which significantly reduced mean WSS by 3.8 Pa. Thus, CFD has the potential to improve post-treatment hemodynamics associated with poor long-term prognosis of patients with coarctation of the aorta. MRI-based CFD has a huge potential to allow the slight reduction of post-treatment pressure drop, which causes significant improvement (reduction) of the WSS at the stenosis segment.

Biodegradable Magnetic Particles for Cellular MRI

NASA Astrophysics Data System (ADS)

Nkansah, Michael Kwasi

Cell transplantation has the potential to treat numerous diseases and injuries. While magnetic particle-enabled, MRI-based cell tracking has proven useful for visualizing the location of cell transplants in vivo, current formulations of particles are either too weak to enable single cell detection or have non-degradable polymer matrices that preclude clinical translation. Furthermore, the off-label use of commercial agents like Feridex®, Bangs beads and ferumoxytol for cell tracking significantly stunts progress in the field, rendering it needlessly susceptible to market externalities. The recent phasing out of Feridex from the market, for example, heightens the need for a dedicated agent specifically designed for MRI-based cell tracking. To this end, we engineered clinically viable, biodegradable particles of iron oxide made using poly(lactide-co-glycolide) (PLGA) and demonstrated their utility in two MRI-based cell tracking paradigms in vivo. Both micro- and nanoparticles (2.1±1.1 μm and 105±37 nm in size) were highly magnetic (56.7-83.7 wt% magnetite), and possessed excellent relaxometry (r2* relaxivities as high as 614.1 s-1mM-1 and 659.1 s -1mM-1 at 4.7 T respectively). Magnetic PLGA micropartides enabled the in vivo monitoring of neural progenitor cell migration to the olfactory bulb in rat brains over 2 weeks at 11.7 T with ˜2-fold greater contrast-to-noise ratio and ˜4-fold better sensitivity at detecting migrated cells in the olfactory bulb than Bangs beads. Highly magnetic PLGA nanoparticles enabled MRI detection (at 11.7 T) of up to 10 rat mesenchymal cells transplanted into rat brain at 100-μm resolution. Highly magnetic PLGA particles were also shown to degrade by 80% in mice liver over 12 weeks in vivo. Moreover, no adverse effects were observed on cellular viability and function in vitro after labeling a wide range of cells. Magnetically labeled rat mesenchymal and neural stem cells retained their ability to differentiate into multiple

Towards magnetic-enhanced cellular uptake, MRI and chemotherapeutics delivery by magnetic mesoporous silica nanoparticles.

PubMed

Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

2012-10-01

A type of nanoparticle with three functional modalities was prepared with the aim of providing a multifunctional drug delivery system. The nanoparticle was 50 nm in size, with 2.7 nm mesopores and a magnetic nanocrystal core, which was further doped with FITC to enable the tracking of cellular uptake. We demonstrated that the internalization of the nanoparticles in tumor cells could be enhanced by applying an external magnetic field and furthermore, this kind of nanoparticle could be used in magnetic targeted drug delivery. With high transverse relaxivity, the magnetic nanoparticles shortened proton relaxation time and induced high magnetic resonance imaging contrast in tumor cells. Studies on anticancer drug loading and delivery capacity of anticancer drugs also showed that this type of nanoparticles could load water-soluble doxorubicin, and produce a prominent inhibitive effect against tumor cells. Taken together, the presented nanoparticles could become a promising agent in cancer theranostics.

Spherical agglomerates of pure drug nanoparticles for improved pulmonary delivery in dry powder inhalers

NASA Astrophysics Data System (ADS)

Hu, Jun; Dong, Yuancai; Pastorin, Giorgia; Ng, Wai Kiong; Tan, Reginald B. H.

2013-04-01

The aim of this study was to produce micron-sized spherical agglomerates of pure drug nanoparticles to achieve improved aerosol performance in dry powder inhalers (DPIs). Sodium cromoglicate was chosen as the model drug. Pure drug nanoparticles were prepared through a bottom-up particle formation process, liquid antisolvent precipitation, and then rapidly agglomerated into porous spherical microparticles by immediate (on-line) spray drying. Nonporous spherical drug microparticles with similar geometric size distribution were prepared by conventional spray drying of the aqueous drug solution, which together with the mechanically micronized drug particles were used as the control samples. The three samples were characterized by field emission scanning electron microscopy, laser diffraction, Brunauer-Emmett-Teller analysis, density measurement, powder X-ray diffraction, and in vitro aerosol deposition measurement with a multistage liquid impinger. It was found that drug nanoparticles with a diameter of 100 nm were precipitated and agglomerated into highly porous spherical microparticles with a volume median diameter ( D 50 %) of 2.25 ± 0.08 μm and a specific surface area of 158.63 ± 3.27 m2/g. In vitro aerosol deposition studies showed the fine particle fraction of such spherical agglomerates of drug nanoparticles was increased by more than 50 % in comparison with the control samples, demonstrating significant improvements in aerosol performance. The results of this study indicated the potential of the combined particle engineering process of liquid antisolvent precipitation followed by immediate (on-line) spray drying in the development of novel DPI drug products with improved aerosol performance.

In-Vivo Imaging of Cell Migration Using Contrast Enhanced MRI and SVM Based Post-Processing.

PubMed

Weis, Christian; Hess, Andreas; Budinsky, Lubos; Fabry, Ben

2015-01-01

The migration of cells within a living organism can be observed with magnetic resonance imaging (MRI) in combination with iron oxide nanoparticles as an intracellular contrast agent. This method, however, suffers from low sensitivity and specificty. Here, we developed a quantitative non-invasive in-vivo cell localization method using contrast enhanced multiparametric MRI and support vector machines (SVM) based post-processing. Imaging phantoms consisting of agarose with compartments containing different concentrations of cancer cells labeled with iron oxide nanoparticles were used to train and evaluate the SVM for cell localization. From the magnitude and phase data acquired with a series of T2*-weighted gradient-echo scans at different echo-times, we extracted features that are characteristic for the presence of superparamagnetic nanoparticles, in particular hyper- and hypointensities, relaxation rates, short-range phase perturbations, and perturbation dynamics. High detection quality was achieved by SVM analysis of the multiparametric feature-space. The in-vivo applicability was validated in animal studies. The SVM detected the presence of iron oxide nanoparticles in the imaging phantoms with high specificity and sensitivity with a detection limit of 30 labeled cells per mm3, corresponding to 19 μM of iron oxide. As proof-of-concept, we applied the method to follow the migration of labeled cancer cells injected in rats. The combination of iron oxide labeled cells, multiparametric MRI and a SVM based post processing provides high spatial resolution, specificity, and sensitivity, and is therefore suitable for non-invasive in-vivo cell detection and cell migration studies over prolonged time periods.

Improving scattering layer through mixture of nanoporous spheres and nanoparticles in ZnO-based dye-sensitized solar cells.

PubMed

Kim, Chohui; Choi, Hongsik; Kim, Jae Ik; Lee, Sangheon; Kim, Jinhyun; Lee, Woojin; Hwang, Taehyun; Kang, Suji; Moon, Taeho; Park, Byungwoo

2014-01-01

A scattering layer is utilized by mixing nanoporous spheres and nanoparticles in ZnO-based dye-sensitized solar cells. Hundred-nanometer-sized ZnO spheres consisting of approximately 35-nm-sized nanoparticles provide not only effective light scattering but also a large surface area. Furthermore, ZnO nanoparticles are added to the scattering layer to facilitate charge transport and increase the surface area as filling up large voids. The mixed scattering layer of nanoparticles and nanoporous spheres on top of the nanoparticle-based electrode (bilayer geometry) improves solar cell efficiency by enhancing both the short-circuit current (J sc) and fill factor (FF), compared to the layer consisting of only nanoparticles or nanoporous spheres.

Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Constantinou, Pamela E.; Danysh, Brian P.; Shenefelt, Derek L.; Carson, Daniel D.; Farach-Carson, Mary C.; Kulchitsky, Vladimir A.; Wu, Xiangwei; Wagner, Daniel S.; Lapotko, Dmitri O.

2012-01-01

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level. PMID:22509318

Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems.

PubMed

Lukianova-Hleb, Ekaterina Y; Ren, Xiaoyang; Constantinou, Pamela E; Danysh, Brian P; Shenefelt, Derek L; Carson, Daniel D; Farach-Carson, Mary C; Kulchitsky, Vladimir A; Wu, Xiangwei; Wagner, Daniel S; Lapotko, Dmitri O

2012-01-01

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level.

In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis.

PubMed

Kirschbaum, Klara; Sonner, Jana K; Zeller, Matthias W; Deumelandt, Katrin; Bode, Julia; Sharma, Rakesh; Krüwel, Thomas; Fischer, Manuel; Hoffmann, Angelika; Costa da Silva, Milene; Muckenthaler, Martina U; Wick, Wolfgang; Tews, Björn; Chen, John W; Heiland, Sabine; Bendszus, Martin; Platten, Michael; Breckwoldt, Michael O

2016-11-15

Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases.

Radiotherapy Improvements by Using Au Nanoparticles.

PubMed

Torrisi, Lorenzo

2015-01-01

Au nanoparticles can be prepared inside biological solutions and incorporated in special molecules for their transport through blood, drugs and proteins up to the tumour sites or directly injected in their volume when it is possible. The Au nanoparticles are biocompatible and can be accepted locally in the organism also at relatively high concentrations. The use of Au nanoparticles injected in the tumour site enhances significantly the effective atomic number of the medium, depending on the used concentration, and consequently the proton and electron energy loss and the X-ray absorption coefficient determining an increment of the local absorbed dose during radiotherapy. Traditional radiotherapy using electrons, X-rays and gamma rays, and innovative protontherapy can benefit the increment of the effective atomic number of the tissue in the presence of Au-nanoparticles embedded in the tumour volume with an adaptive up-take procedure. This method decreases the dose released to the healthy tissues permitting a better cantering of the irradiated targets and shielding the healthy tissue placed behind the tumour. The presented theoretical study approach permits to evaluate an enhancement of the radiotherapy dose of the order of 1 % using 60 MeV protons, of the order of 10% using 6 MeV electrons and of the order of 100 % using 100 keV X-ray photons. Here, we also disccused for patents relaed to the topic.

Creeping flashover characteristics improvement of nanofluid/pressboard system with TiO2 nanoparticles

NASA Astrophysics Data System (ADS)

Huang, Meng; Wang, Lei; Ge, Yang; Lv, Yu-zhen; Qi, Bo; Li, Cheng-rong

2018-03-01

Creeping flashover easily occurs at the interface between oil and pressboard in transformer and thus results in outage of power transmission system. Investigations have shown that creeping flashover characteristics at oil/pressboard interface can be improved by the addition of TiO2 nanoparticles, but the mechanism is still not thoroughly known. In this work, creeping flashover performance at nanofluid/pressboard interface modified by different sizes of nanoparticles were studied and the mechanism was presented as well. Nanofluids with the same concentration but with different sizes of TiO2 nanoparticles were prepared, and pressboards impregnated with them were prepared as well. After that, their creeping flashover characteristics were measured and compared. Nanoparticle's size affected the creeping flashover performance along oil/pressboard greatly under both AC and lightning impulse voltages. The highest creeping flashover voltage can be enhanced by as high as 12.2% and 32.0% respectively. The underlying electric field distribution and charge transportation behaviors were analyzed to demonstrate the influence of nanoparticle's size. By the addition of nanoparticles with a smaller size, the dielectric constant of nanofluid was increased closer to that of the pressboard, thus they were matched better. Moreover, charge was easier to dissipate from the oil/pressboard interface and electric field distortion at the interface was consequently reduced. Therefore, the electric field was more like a uniform field and the forward development of flashover was more difficult, leading to a better performance of creeping flashover of oil-impregnated pressboard.

Synthesis of improved upconversion nanoparticles as ultrasensitive fluorescence probe for mycotoxins.

PubMed

Chen, Quansheng; Hu, Weiwei; Sun, Cuicui; Li, Huanhuan; Ouyang, Qin

2016-09-28

Rare earth-doped upconversion nanoparticles (UCNPs) have promising potentials in biodetection due to their unique frequency upconverting capability and high detection sensitivity. This paper reports an improved UCNPs-based fluorescence probe for dual-sensing of Aflatoxin B1 (AFB1) and Deoxynivalenol (DON) using a magnetism-induced separation and the specific formation of antibody-targets complex. Herein, the improved UCNPs, which were namely NaYF4:Yb/Ho/Gd and NaYF4:Yb/Tm/Gd, were systematically studied based on the optimization of reaction time, temperature and the concentration of dopant ions with simultaneous phase and size controlled NaYF4 nanoparticles; and the targets were detected using the pattern of competitive combination assay. Under an optimized condition, the advanced fluorescent probes revealed stronger fluorescent properties, broader biological applications and better storage stabilities compared to traditional UCNPs-based ones; and ultrasensitive determinations of AFB1 and DON were achieved under a wide sensing range of 0.001-0.1 ng ml(-1) with the limit of detection (LOD) of 0.001 ng ml(-1). Additionally, the applicability of the improved nanosensor for the detection of mycotoxins was also confirmed in adulterated oil samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron oxide core oil-in-water emulsions as a multifunctional nanoparticle platform for tumor targeting and imaging

PubMed Central

Jarzyna, Peter A.; Skajaa, Torjus; Gianella, Anita; Cormode, David P.; Samber, Dan D.; Dickson, Stephen D.; Chen, Wei; Griffioen, Arjan W.; Fayad, Zahi A.; Mulder, Willem J. M.

2009-01-01

Nanoemulsions are increasingly investigated for the delivery of hydrophobic drugs to improve their bioavailability or make their administration possible. In the current study, oil-in-water emulsions with three different mean diameters (30, 60, and 95 nm) were developed as a new multimodality nanoparticle platform for tumor targeting and imaging. To that aim, hydrophobically coated iron oxide particles were included in the soybean oil core of the nanoemulsions to enable their detection with magnetic resonance imaging (MRI), while the conjugation of a near infrared fluorophore allowed optical imaging. The accumulation of this novel nanocomposite in subcutaneous human tumors in nude mice was demonstrated with MRI and fluorescence imaging in vivo, and with Perl’s staining of histological tumor sections ex vivo. PMID:19783295

Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice

PubMed Central

Majmudar, Maulik D.; Keliher, Edmund J.; Heidt, Timo; Leuschner, Florian; Truelove, Jessica; Sena, Brena F.; Gorbatov, Rostic; Iwamoto, Yoshiko; Dutta, Partha; Wojtkiewicz, Gregory; Courties, Gabriel; Sebas, Matt; Borodovsky, Anna; Fitzgerald, Kevin; Nolte, Marc W.; Dickneite, Gerhard; Chen, John W.; Anderson, Daniel G.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

2013-01-01

Background Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. We here employed nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6Chigh monocyte subset traffic, to reduce infarct inflammation in apoE−/− mice after MI. We used dual target PET/MRI of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset-targeted RNAi altered infarct inflammation and healing. Methods and Results Flow cytometry, gene expression analysis and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE−/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix crosslinking non-invasively, we developed a fluorine-18 labeled PET agent (18F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged using a molecular MRI sensor of MPO activity (MPO-Gd). PET/MRI detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal, p<0.05) while 18F-FXIII PET reflected unimpeded matrix crosslinking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29 to 35% (p<0.05). Conclusion CCR2 targeted RNAi reduced recruitment of Ly-6Chigh monocytes, attenuated infarct inflammation and curbed post-MI left ventricular remodeling. PMID:23616627

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs).

PubMed

Shevtsov, Maxim; Nikolaev, Boris; Marchenko, Yaroslav; Yakovleva, Ludmila; Skvortsov, Nikita; Mazur, Anton; Tolstoy, Peter; Ryzhov, Vyacheslav; Multhoff, Gabriele

2018-01-01

Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI). Synthesized hybrid chitosan-dextran superparamagnetic nanoparticles (CS-DX-SPIONs) were characterized using transmission electron microscopy (TEM) and relaxometry studies. Nonlinear magnetic response measurements were employed for confirming the superparamagnetic state of particles. Following in vitro analysis of nanoparticles cellular uptake tumor targeting was assessed in the model of the orthotopic glioma in rodents. CS-DX-SPIONs nanoparticles showed a uniform diameter of 55 nm under TEM and superparamagentic characteristics as determined by T 1 (spin-lattice relaxation time) and T 2 (spin-spin relaxation time) proton relaxation times. Application of the chitosan increased the charge from +8.9 to +19.3 mV of the dextran-based SPIONs. The nonlinear magnetic response at second harmonic of CS-DX-SPIONs following the slow change of stationary magnetic fields with very low hysteresis evidenced superparamagnetic state of particles at ambient temperatures. Confocal microscopy and flow cytometry studies showed an enhanced internalization of the chitosan-based nanoparticles in U87, C6 glioma and HeLa cells as compared to dextran-coated particles. Cytotoxicity assay demonstrated acceptable toxicity profile of the synthesized nanoparticles up to a concentration of 10 μg/ml. Intravenously administered CS-DX-SPIONs in orthotopic C6 gliomas in rats accumulated in the tumor site as shown by high-resolution MRI (11.0 T). Retention of nanoparticles resulted in a significant contrast enhancement of the tumor image that was accompanied with a dramatic drop in T 2 values ( P <0.001). Subsequent histological studies proved the accumulation of the nanoparticles inside

Diffuse intrinsic pontine glioma: is MRI surveillance improved by region of interest volumetry?

PubMed

Riley, Garan T; Armitage, Paul A; Batty, Ruth; Griffiths, Paul D; Lee, Vicki; McMullan, John; Connolly, Daniel J A

2015-02-01

Paediatric diffuse intrinsic pontine glioma (DIPG) is noteworthy for its fibrillary infiltration through neuroparenchyma and its resultant irregular shape. Conventional volumetry methods aim to approximate such irregular tumours to a regular ellipse, which could be less accurate when assessing treatment response on surveillance MRI. Region-of-interest (ROI) volumetry methods, using manually traced tumour profiles on contiguous imaging slices and subsequent computer-aided calculations, may prove more reliable. To evaluate whether the reliability of MRI surveillance of DIPGs can be improved by the use of ROI-based volumetry. We investigated the use of ROI- and ellipsoid-based methods of volumetry for paediatric DIPGs in a retrospective review of 22 MRI examinations. We assessed the inter- and intraobserver variability of the two methods when performed by four observers. ROI- and ellipsoid-based methods strongly correlated for all four observers. The ROI-based volumes showed slightly better agreement both between and within observers than the ellipsoid-based volumes (inter-[intra-]observer agreement 89.8% [92.3%] and 83.1% [88.2%], respectively). Bland-Altman plots show tighter limits of agreement for the ROI-based method. Both methods are reproducible and transferrable among observers. ROI-based volumetry appears to perform better with greater intra- and interobserver agreement for complex-shaped DIPG.

Improved i.p. drug delivery with bioadhesive nanoparticles

PubMed Central

Deng, Yang; Yang, Fan; Cocco, Emiliano; Song, Eric; Zhang, Junwei; Cui, Jiajia; Mohideen, Muneeb; Bellone, Stefania; Santin, Alessandro D.; Saltzman, W. Mark

2016-01-01

The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space. BNPs loaded with a potent chemotherapeutic agent [epothilone B (EB)] showed significantly lower systemic toxicity and higher therapeutic efficacy against i.p. chemotherapy-resistant uterine serous carcinoma-derived xenografts compared with free EB and non-BNPs loaded with EB. PMID:27663731

Development of magnetic resonance imaging based detection methods for beta amyloids via sialic acid-functionalized magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Kouyoumdjian, Hovig

The development of a non-invasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding preventive treatment of the disease. The aggregates of beta amyloids are a pathological hallmark of Alzheimer's disease. Carbohydrates such as sialic acid terminated gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using sialic acid coated iron oxide superparamagnetic nanoparticles for in vitro detection in addition to the assessment of the in vivo mouse-BBB (Blood brain barrier) crossing of the BSA (bovine serum albumin)-modified ones. The sialic acid functionalized dextran nanoparticles were shown to bind with beta amyloids through several techniques including ELISA (enzyme linked immunosorbent assay), MRI (magnetic resonance imaging), TEM (transmission electron microscopy), gel electrophoresis and tyrosine fluorescence assay. The superparamagnetic nature of the nanoparticles allowed easy detection of the beta amyloids in mouse brains in both in vitro and ex vivo model by magnetic resonance imaging. Furthermore, the sialic acid nanoparticles greatly reduced beta amyloid induced cytotoxicity to SH-SY5Y neuroblastoma cells, highlighting the potential of the glyconanoparticles for detection and imaging of beta amyloids. Sialic acid functionalized BSA (bovine serum albumin) nanoparticles also showed significant binding to beta amyloids, through ELISA and ex vivo mouse brain MRI experiments. Alternatively, the BBB crossing was demonstrated by several techniques such as confocal microscopy, endocytosis, exocytosis assays and were affirmed by nanoparticles transcytosis assays through bEnd.3 endothelial cells. Finally, the BBB crossing was confirmed by analyzing the MRI signal of nanoparticle-injected CD-1 mice.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy (abstract)

NASA Astrophysics Data System (ADS)

Lee, Dongkyu; Maeng, Inhee; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol; Son, Joo-Hiuk

2009-04-01

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd2O3) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

Recent Development of Inorganic Nanoparticles for Biomedical Imaging

PubMed Central

2018-01-01

Inorganic nanoparticle-based biomedical imaging probes have been studied extensively as a potential alternative to conventional molecular imaging probes. Not only can they provide better imaging performance but they can also offer greater versatility of multimodal, stimuli-responsive, and targeted imaging. However, inorganic nanoparticle-based probes are still far from practical use in clinics due to safety concerns and less-optimized efficiency. In this context, it would be valuable to look over the underlying issues. This outlook highlights the recent advances in the development of inorganic nanoparticle-based probes for MRI, CT, and anti-Stokes shift-based optical imaging. Various issues and possibilities regarding the construction of imaging probes are discussed, and future research directions are suggested. PMID:29632878

R1 dispersion contrast at high field with fast field-cycling MRI

NASA Astrophysics Data System (ADS)

Bödenler, Markus; Basini, Martina; Casula, Maria Francesca; Umut, Evrim; Gösweiner, Christian; Petrovic, Andreas; Kruk, Danuta; Scharfetter, Hermann

2018-05-01

Contrast agents with a strong R1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R1 dispersion imaging and demonstrate the capability of generating R1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R1 dispersion at a field strength of 3 T.

Understanding the Benefits and Limitations of Magnetic Nanoparticle Heating for Improved Applications in Cancer Hyperthermia and Biomaterial Cryopreservation

NASA Astrophysics Data System (ADS)

Etheridge, Michael L.

The current work focused on the ability of magnetic nanoparticles to produce heat in the presence of an applied alternating magnetic field. Magnetic nanoparticle hyperthermia applications utilize this behavior to treat cancer and this approach has received clinical approval in the European Union, but significant developments are necessary for this technology to have a chance for wider-spread acceptance. Here then we begin by investigating some of the important limitations of the current technology. By characterizing the ability of superparamagnetic and ferromagnetic nanoparticles to heat under a range of applied fields, we are able to determine the optimal field settings for clinical application and make recommendations on the highest impact strategies to increase heating. In addition, we apply these experimentally determined limits to heating in a series of heat transfer models, to demonstrate the therapeutic impact of nanoparticle concentration, target volume, and delivery strategy. Next, we attempt to address one of the key questions facing the field- what is the impact of biological aggregation on heating? Controlled aggregate populations are produced and characterized in ionic and protein solutions and their heating is compared with nanoparticles incubated in cellular suspensions. Through this investigation we are able to demonstrate that aggregation is responsible for up to a 50% decrease in heating. However, more importantly, we are able to demonstrate that the observed reductions in heating correlate with reductions in longitudinal relaxation (T1) measured by sweep imaging with Fourier transformation (SWIFT) magnetic resonance imaging (MRI), providing a potential platform to account for these aggregation effects and directly predict heating in a clinical setting. Finally, we present a new application for magnetic nanoparticle heating, in the thawing of cryopreserved biomaterials. A number of groups have demonstrated the ability to rapidly cool and preserve

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

NASA Astrophysics Data System (ADS)

Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

2015-04-01

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time.

Improved anode materials for lithium-ion batteries comprise non-covalently bonded graphene and silicon nanoparticles

NASA Astrophysics Data System (ADS)

Ye, Yun-Sheng; Xie, Xiao-Lin; Rick, John; Chang, Feng-Chih; Hwang, Bing-Joe

2014-02-01

Si, when compared to conventional graphite, offers an order-of-magnitude improvement as a high capacity anode material for Li-ion batteries. Despite significant advances in nanostructured Si-based anodes, the formation of stable Si anodes remains a challenge, due to the significant volume changes that occur during lithiation and delithiation. Si/graphene composites, with graphene sheets and Si nanoparticles bound in a dispersion obtained by a self-assembly technique using non-covalent electrostatic attraction (following thermal processing to remove residual organic material) are used to prepare Si-based anodes for use in Li-ion batteries. A mesoporous structure, obtained by further thermal processing is able to accommodate large Si nanoparticle volume changes during cycling, thereby facilitating Li-ion diffusion within the electrode. Morphological analysis showed that Si nanoparticles are homogeneously distributed on the graphene sheets, which is thought to account for the excellent electrochemical performance of the resulting Si/graphene composite. A composite containing Si 67.3 wt% exhibits a greatly improved capacity and cycling stability in comparison with bare Si in combination with the thermal reduction of a simple mixture of graphene oxide and Si nanoparticles without electrostatic attraction (Si content = 64.6 wt%; capacity of 512 mAh g-1 in 40th cycle).

Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI

NASA Astrophysics Data System (ADS)

Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

2016-10-01

Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7  ±  1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n  =  9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland-Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were  -31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and  -10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p  =  0.0085) and HA fraction (p  <  0.0001), but not other parameters. Improved mean differences and Bland-Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.

MRI micturating urethrography for improved urethral delineation in prostate radiotherapy planning: a case study

NASA Astrophysics Data System (ADS)

Rai, Robba; Sidhom, Mark; Lim, Karen; Ohanessian, Lucy; Liney, Gary P.

2017-04-01

Stereotactic ablative body radiotherapy is used in prostate cancer to deliver a high dose of radiation to the tumour over a small number of treatments. This involves the simulation of the patient using both CT and MRI. Current practice is to insert an indwelling catheter (IDC) during CT to assist with visualisation of the urethra and subsequently minimise dose to this highly critical structure. However, this procedure is invasive and has an associated risk of infection. This is a case study, which demonstrates our initial experience of using a real-time non-invasive MRI technique to replace the use of IDC for prostate cancer patients. The patient was scanned on a dedicated 3T MRI and was instructed to micturate in their own time whereupon a sagittal T2 weighted HASTE sequence was acquired every 5 s. This was subsequently followed by T2 weighted axial imaging at the level of mid prostate to provide improved urethral definition. Acquired images showed bladder voidance in real-time and an increase in signal intensity in the proximal urethra post voiding allowing for delineation of the urethra. The dimension and shape of the proximal urethra was well visualised and accumulation time of urine in the urethra was sufficient to enable optimum timing of the scanning technique. We have presented for the first time a micturating urethography technique using MRI, which has allowed us to visualise the urethra without contrast and with minimal invasiveness to the patient.

An improved DNA force field for ssDNA interactions with gold nanoparticles

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

Jiang, Xiankai; Huai, Ping; Fan, Chunhai

The widespread applications of single-stranded DNA (ssDNA) conjugated gold nanoparticles (AuNPs) have spurred an increasing interest in the interactions between ssDNA and AuNPs. Despite extensive studies using the most sophisticated experimental techniques, the detailed molecular mechanisms still remain largely unknown. Large scale molecular dynamics (MD) simulations can thus be used to supplement experiments by providing complementary information about ssDNA-AuNP interactions. However, up to now, all modern force fields for DNA were developed based on the properties of double-stranded DNA (dsDNA) molecules, which have hydrophilic outer backbones “protecting” hydrophobic inner nucleobases from water. Without the double-helix structure of dsDNA and thusmore » the “protection” by the outer backbone, the nucleobases of ssDNA are directly exposed to solvent, and their behavior in water is very different from that of dsDNA, especially at the interface with nanoparticles. In this work, we have improved the force field of ssDNA for use with nanoparticles, such as AuNPs, based on recent experimental results and quantum mechanics calculations. With the new improved force field, we demonstrated that a poly(A) sequence adsorbed on a AuNP surface is much more stable than a poly(T) sequence, which is consistent with recent experimental observations. On the contrary, the current standard force fields, including AMBER03, CHARMM27, and OPLSAA, all gave erroneous results as compared to experiments. The current improved force field is expected to have wide applications in the study of ssDNA with nanomaterials including AuNPs, which might help promote the development of ssDNA-based biosensors and other bionano-devices.« less

An improved DNA force field for ssDNA interactions with gold nanoparticles

NASA Astrophysics Data System (ADS)

Jiang, Xiankai; Gao, Jun; Huynh, Tien; Huai, Ping; Fan, Chunhai; Zhou, Ruhong; Song, Bo

2014-06-01

The widespread applications of single-stranded DNA (ssDNA) conjugated gold nanoparticles (AuNPs) have spurred an increasing interest in the interactions between ssDNA and AuNPs. Despite extensive studies using the most sophisticated experimental techniques, the detailed molecular mechanisms still remain largely unknown. Large scale molecular dynamics (MD) simulations can thus be used to supplement experiments by providing complementary information about ssDNA-AuNP interactions. However, up to now, all modern force fields for DNA were developed based on the properties of double-stranded DNA (dsDNA) molecules, which have hydrophilic outer backbones "protecting" hydrophobic inner nucleobases from water. Without the double-helix structure of dsDNA and thus the "protection" by the outer backbone, the nucleobases of ssDNA are directly exposed to solvent, and their behavior in water is very different from that of dsDNA, especially at the interface with nanoparticles. In this work, we have improved the force field of ssDNA for use with nanoparticles, such as AuNPs, based on recent experimental results and quantum mechanics calculations. With the new improved force field, we demonstrated that a poly(A) sequence adsorbed on a AuNP surface is much more stable than a poly(T) sequence, which is consistent with recent experimental observations. On the contrary, the current standard force fields, including AMBER03, CHARMM27, and OPLSAA, all gave erroneous results as compared to experiments. The current improved force field is expected to have wide applications in the study of ssDNA with nanomaterials including AuNPs, which might help promote the development of ssDNA-based biosensors and other bionano-devices.

An improved DNA force field for ssDNA interactions with gold nanoparticles.

PubMed

Jiang, Xiankai; Gao, Jun; Huynh, Tien; Huai, Ping; Fan, Chunhai; Zhou, Ruhong; Song, Bo

2014-06-21

The widespread applications of single-stranded DNA (ssDNA) conjugated gold nanoparticles (AuNPs) have spurred an increasing interest in the interactions between ssDNA and AuNPs. Despite extensive studies using the most sophisticated experimental techniques, the detailed molecular mechanisms still remain largely unknown. Large scale molecular dynamics (MD) simulations can thus be used to supplement experiments by providing complementary information about ssDNA-AuNP interactions. However, up to now, all modern force fields for DNA were developed based on the properties of double-stranded DNA (dsDNA) molecules, which have hydrophilic outer backbones "protecting" hydrophobic inner nucleobases from water. Without the double-helix structure of dsDNA and thus the "protection" by the outer backbone, the nucleobases of ssDNA are directly exposed to solvent, and their behavior in water is very different from that of dsDNA, especially at the interface with nanoparticles. In this work, we have improved the force field of ssDNA for use with nanoparticles, such as AuNPs, based on recent experimental results and quantum mechanics calculations. With the new improved force field, we demonstrated that a poly(A) sequence adsorbed on a AuNP surface is much more stable than a poly(T) sequence, which is consistent with recent experimental observations. On the contrary, the current standard force fields, including AMBER03, CHARMM27, and OPLSAA, all gave erroneous results as compared to experiments. The current improved force field is expected to have wide applications in the study of ssDNA with nanomaterials including AuNPs, which might help promote the development of ssDNA-based biosensors and other bionano-devices.

High-Resolution Magnetic Resonance Imaging Enhanced With Superparamagnetic Nanoparticles Measures Macrophage Burden in Atherosclerosis

PubMed Central

Morishige, Kunio; Kacher, Daniel F.; Libby, Peter; Josephson, Lee; Ganz, Peter; Weissleder, Ralph; Aikawa, Masanori

2010-01-01

Background Macrophages contribute to the progression and acute complications of atherosclerosis. Macrophage imaging may serve as a biomarker to identify subclinical inflamed lesions, to predict future risk, and to aid in the assessment of novel therapies. Methods and Results To test the hypothesis that nanoparticle-enhanced, high-resolution magnetic resonance imaging (MRI) can measure plaque macrophage accumulation, we used 3-T MRI with a macrophage-targeted superparamagnetic nanoparticle preparation (monocrystalline iron oxide nanoparticles-47 [MION-47]) in cholesterol-fed New Zealand White rabbits 6 months after balloon injury. In vivo MRI visualized thickened abdominal aortas on both T1- and T2-weighted spin-echo images (T1 spin echo, 20 axial slices per animal; T2 spin echo, 28 slices per animal). Seventy-two hours after MION-47 injection, aortas exhibited lower T2 signal intensity compared with before contrast imaging (signal intensity ratio, aortic wall/muscle: before, 1.44±0.26 versus after, 0.95±0.22; 164 slices; P<0.01), whereas T1 spin echo images showed no significant change. MRI on ex vivo specimens provided similar results. Histological studies colocalized iron accumulation with immunoreactive macrophages in atheromata. The magnitude of signal intensity reduction on T2 spin echo in vivo images further correlated with macrophage areas in situ (150 slices; r=0.73). Treatment with rosuvastatin for 3 months yielded diminished macrophage content (P<0.05) and reversed T2 signal intensity changes (P<0.005). Signal changes in rosuvastatin-treated rabbits correlated with reduced macrophage burden (r=0.73). In vitro validation studies showed concentration-dependent MION-47 uptake by human primary macrophages. Conclusion The magnitude of T2 signal intensity reduction in high-resolution MRI after administration of superparamagnetic phagocytosable nanoparticles can assess macrophage burden in atheromata, providing a clinically translatable tool to identify

Co-immobilization of gold nanoparticles with glucose oxidase to improve bioelectrocatalytic glucose oxidation

NASA Astrophysics Data System (ADS)

Aquino Neto, Sidney; Milton, Ross D.; Crepaldi, Laís B.; Hickey, David P.; de Andrade, Adalgisa R.; Minteer, Shelley D.

2015-07-01

Recently, there has been much effort in developing metal nanoparticle catalysts for fuel oxidation, as well as the development of enzymatic bioelectrocatalysts for fuel oxidation. However, there has been little study of the synergy of hybrid electrocatalytic systems. We report the preparation of hybrid bioanodes based on Au nanoparticles supported on multi-walled carbon nanotubes (MWCNTs) co-immobilized with glucose oxidase (GOx). Mediated electron transfer was achieved by two strategies: ferrocene entrapped within polypyrrole and a ferrocene-modified linear poly(ethylenimine) (Fc-LPEI) redox polymer. Electrochemical characterization of the Au nanoparticles supported on MWCNTs indicate that this catalyst exhibits an electrocatalytic response for glucose even in acidic conditions. Using the redox polymer Fc-LPEI as the mediator, voltammetric and amperometric data demonstrated that these bioanodes can efficiently achieve mediated electron transfer and also indicated higher catalytic currents with the hybrid bioelectrode. From the amperometry, the maximum current density (Jmax) achieved with the hybrid bioelectrode was 615 ± 39 μA cm-2, whereas the bioanode employing GOx only achieved a Jmax of 409 ± 26 μA cm-2. Biofuel cell tests are consistent with the electrochemical characterization, thus confirming that the addition of the metallic species into the bioanode structure can improve fuel oxidation and consequently, improve the power generated by the system.

Improved Tribological Performance of Amorphous Carbon (a-C) Coating by ZrO₂ Nanoparticles.

PubMed

Tang, Jinzhu; Ding, Qi; Zhang, Songwei; Wu, Guizhi; Hu, Litian

2016-09-22

Nanomaterials, such as Graphene, h-BN nanoparticles and MoS₂ nanotubes, have shown their ability in improving the tribological performance of amorphous carbon (a-C) coatings. In the current study, the effectiveness of ZrO₂ nanoparticles (ZrO₂-NPs) in lubricating the self-mated nonhydrogenated a-C contacts was investigated in boundary lubrication regime. The results showed that 13% less friction and 50% less wear compared to the base oil were achieved by employing ZrO₂-NPs in the base oil in self-mated a-C contacts. Via analyzing the ZrO₂-NPs and the worn a-C surface after tests, it was found that the improved lubrication by ZrO₂-NPs was based on "polishing effects", which is a new phenomenon observed between a-C and nanoparticles. Under the "polishing effect", micro-plateaus with extremely smooth surface and uniform height were produced on the analyzed a-C surface. The resulting topography of the a-C coating is suitable for ZrO₂-NPs to act as nano-bearings between rubbing surfaces. Especially, the ZrO₂-NPs exhibited excellent mechanical and chemical stability, even under the severe service condition, suggesting that the combination of nonhydrogenated a-C coating with ZrO₂-NPs is an effective, long lasting and environment-friendly lubrication solution.

Introduction to metallic nanoparticles

PubMed Central

Mody, Vicky V.; Siwale, Rodney; Singh, Ajay; Mody, Hardik R.

2010-01-01

Metallic nanoparticles have fascinated scientist for over a century and are now heavily utilized in biomedical sciences and engineering. They are a focus of interest because of their huge potential in nanotechnology. Today these materials can be synthesized and modified with various chemical functional groups which allow them to be conjugated with antibodies, ligands, and drugs of interest and thus opening a wide range of potential applications in biotechnology, magnetic separation, and preconcentration of target analytes, targeted drug delivery, and vehicles for gene and drug delivery and more importantly diagnostic imaging. Moreover, various imaging modalities have been developed over the period of time such as MRI, CT, PET, ultrasound, SERS, and optical imaging as an aid to image various disease states. These imaging modalities differ in both techniques and instrumentation and more importantly require a contrast agent with unique physiochemical properties. This led to the invention of various nanoparticulated contrast agent such as magnetic nanoparticles (Fe3O4), gold, and silver nanoparticles for their application in these imaging modalities. In addition, to use various imaging techniques in tandem newer multifunctional nanoshells and nanocages have been developed. Thus in this review article, we aim to provide an introduction to magnetic nanoparticles (Fe3O4), gold nanoparticles, nanoshells and nanocages, and silver nanoparticles followed by their synthesis, physiochemical properties, and citing some recent applications in the diagnostic imaging and therapy of cancer. PMID:21180459

PROPELLER technique to improve image quality of MRI of the shoulder.

PubMed

Dietrich, Tobias J; Ulbrich, Erika J; Zanetti, Marco; Fucentese, Sandro F; Pfirrmann, Christian W A

2011-12-01

The purpose of this article is to evaluate the use of the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique for artifact reduction and overall image quality improvement for intermediate-weighted and T2-weighted MRI of the shoulder. One hundred eleven patients undergoing MR arthrography of the shoulder were included. A coronal oblique intermediate-weighted turbo spin-echo (TSE) sequence with fat suppression and a sagittal oblique T2-weighted TSE sequence with fat suppression were obtained without (standard) and with the PROPELLER technique. Scanning time increased from 3 minutes 17 seconds to 4 minutes 17 seconds (coronal oblique plane) and from 2 minutes 52 seconds to 4 minutes 10 seconds (sagittal oblique) using PROPELLER. Two radiologists graded image artifacts, overall image quality, and delineation of several anatomic structures on a 5-point scale (5, no artifact, optimal diagnostic quality; and 1, severe artifacts, diagnostically not usable). The Wilcoxon signed rank test was used to compare the data of the standard and PROPELLER images. Motion artifacts were significantly reduced in PROPELLER images (p < 0.001). Observer 1 rated motion artifacts with diagnostic impairment in one patient on coronal oblique PROPELLER images compared with 33 patients on standard images. Ratings for the sequences with PROPELLER were significantly better for overall image quality (p < 0.001). Observer 1 noted an overall image quality with diagnostic impairment in nine patients on sagittal oblique PROPELLER images compared with 23 patients on standard MRI. The PROPELLER technique for MRI of the shoulder reduces the number of sequences with diagnostic impairment as a result of motion artifacts and increases image quality compared with standard TSE sequences. PROPELLER sequences increase the acquisition time.

Superparamagnetic nanoparticles for enhanced magnetic resonance and multimodal imaging

NASA Astrophysics Data System (ADS)

Sikma, Elise Ann Schultz

Magnetic resonance imaging (MRI) is a powerful tool for noninvasive tomographic imaging of biological systems with high spatial and temporal resolution. Superparamagnetic (SPM) nanoparticles have emerged as highly effective MR contrast agents due to their biocompatibility, ease of surface modification and magnetic properties. Conventional nanoparticle contrast agents suffer from difficult synthetic reproducibility, polydisperse sizes and weak magnetism. Numerous synthetic techniques and nanoparticle formulations have been developed to overcome these barriers. However, there are still major limitations in the development of new nanoparticle-based probes for MR and multimodal imaging including low signal amplification and absence of biochemical reporters. To address these issues, a set of multimodal (T2/optical) and dual contrast (T1/T2) nanoparticle probes has been developed. Their unique magnetic properties and imaging capabilities were thoroughly explored. An enzyme-activatable contrast agent is currently being developed as an innovative means for early in vivo detection of cancer at the cellular level. Multimodal probes function by combining the strengths of multiple imaging techniques into a single agent. Co-registration of data obtained by multiple imaging modalities validates the data, enhancing its quality and reliability. A series of T2/optical probes were successfully synthesized by attachment of a fluorescent dye to the surface of different types of nanoparticles. The multimodal nanoparticles generated sufficient MR and fluorescence signal to image transplanted islets in vivo. Dual contrast T1/T2 imaging probes were designed to overcome disadvantages inherent in the individual T1 and T2 components. A class of T1/T2 agents was developed consisting of a gadolinium (III) complex (DTPA chelate or DO3A macrocycle) conjugated to a biocompatible silica-coated metal oxide nanoparticle through a disulfide linker. The disulfide linker has the ability to be reduced

Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance.

PubMed

Strohbehn, Garth; Coman, Daniel; Han, Liang; Ragheb, Ragy R T; Fahmy, Tarek M; Huttner, Anita J; Hyder, Fahmeed; Piepmeier, Joseph M; Saltzman, W Mark; Zhou, Jiangbing

2015-02-01

Current therapy for glioblastoma multiforme (GBM) is largely ineffective, with nearly universal tumor recurrence. The failure of current therapy is primarily due to the lack of approaches for the efficient delivery of therapeutics to diffuse tumors in the brain. In our prior study, we developed brain-penetrating nanoparticles that are capable of penetrating brain tissue and distribute over clinically relevant volumes when administered via convection-enhanced delivery (CED). We demonstrated that these particles are capable of efficient delivery of chemotherapeutics to diffuse tumors in the brain, indicating that they may serve as a groundbreaking approach for the treatment of GBM. In the original study, nanoparticles in the brain were imaged using positron emission tomography (PET). However, clinical translation of this delivery platform can be enabled by engineering a non-invasive detection modality using magnetic resonance imaging (MRI). For this purpose, we developed chemistry to incorporate superparamagnetic iron oxide (SPIO) into the brain-penetrating nanoparticles. We demonstrated that SPIO-loaded nanoparticles, which retain the same morphology as nanoparticles without SPIO, have an excellent transverse (T(2)) relaxivity. After CED, the distribution of nanoparticles in the brain (i.e., in the vicinity of injection site) can be detected using MRI and the long-lasting signal attenuation of SPIO-loaded brain-penetrating nanoparticles lasted over a one-month timecourse. Development of these nanoparticles is significant as, in future clinical applications, co-administration of SPIO-loaded nanoparticles will allow for intraoperative monitoring of particle distribution in the brain to ensure drug-loaded nanoparticles reach tumors as well as for monitoring the therapeutic benefit with time and to evaluate tumor relapse patterns.

[Fusion of MRI, fMRI and intraoperative MRI data. Methods and clinical significance exemplified by neurosurgical interventions].

PubMed

Moche, M; Busse, H; Dannenberg, C; Schulz, T; Schmitgen, A; Trantakis, C; Winkler, D; Schmidt, F; Kahn, T

2001-11-01

The aim of this work was to realize and clinically evaluate an image fusion platform for the integration of preoperative MRI and fMRI data into the intraoperative images of an interventional MRI system with a focus on neurosurgical procedures. A vertically open 0.5 T MRI scanner was equipped with a dedicated navigation system enabling the registration of additional imaging modalities (MRI, fMRI, CT) with the intraoperatively acquired data sets. These merged image data served as the basis for interventional planning and multimodal navigation. So far, the system has been used in 70 neurosurgical interventions (13 of which involved image data fusion--requiring 15 minutes extra time). The augmented navigation system is characterized by a higher frame rate and a higher image quality as compared to the system-integrated navigation based on continuously acquired (near) real time images. Patient movement and tissue shifts can be immediately detected by monitoring the morphological differences between both navigation scenes. The multimodal image fusion allowed a refined navigation planning especially for the resection of deeply seated brain lesions or pathologies close to eloquent areas. Augmented intraoperative orientation and instrument guidance improve the safety and accuracy of neurosurgical interventions.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle

NASA Astrophysics Data System (ADS)

Ahmad, Md. Wasi; Xu, Wenlong; Kim, Sung June; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Park, Ji Ae; Kim, Tae Jeong; Lee, Gang Ho

2015-02-01

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26-38 s-1mM-1 and r2/r1 = 1.4-1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

Improving surface-enhanced Raman scattering properties of TiO(2) nanoparticles by metal Co doping.

PubMed

Yang, Libin; Qin, Xiaoyu; Gong, Mengdi; Jiang, Xin; Yang, Ming; Li, Xiuling; Li, Guangzhi

2014-04-05

In this paper, pure and different amount Co ions doped TiO2 nanoparticles were synthesized by a sol-hydrothermal method and were served as SERS-active substrate. The effect of metal Co doping on SERS properties of TiO2 nanoparticles was mostly investigated. The results indicate that abundant metal doping energy levels can be formed in the energy gap of TiO2 by an appropriate amount Co ions doping, which can promote the charge transfer from TiO2 to molecule, and subsequently enhance SERS signal of adsorbed molecule on TiO2 substrate, and improve remarkably SERS properties of TiO2 nanoparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo.

PubMed

Wang, Yanhua; Hao, Hang; Liu, Haoming; Wang, Yifan; Li, Yan; Yang, Gaojie; Ma, Jun; Mao, Chuanbin; Zhang, Shengmin

2015-08-26

Selenite-doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation-mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnolol Nanoparticles Exhibit Improved Water Solubility and Suppress TNF-α-Induced VCAM-1 Expression in Endothelial Cells.

PubMed

Lee, Chiang-Wen; Hu, Stephen Chu-Sung; Yen, Feng-Lin; Hsu, Lee-Fen; Lee, I-Ta; Lin, Zih-Chan; Tsai, Ming-Horng; Huang, Chieh-Liang; Liang, Chan-Jung; Chiang, Yao-Chang

2017-03-01

The expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells enables the attachment of leukocytes to the endothelium, which may lead to inflammation and the development of atherosclerosis. Magnolol is a major bioactive compound derived from the plant species Magnolia officinalis. In this study, we synthesized a novel nanoparticle formulation of magnolol to improve its water solubility and physicochemical properties, evaluated its effects on TNF-α-induced VCAM-1 expression in endothelial cells, and determined the signal transduction pathways involved. Our findings demonstrated that the magnolol nanoparticle system showed great improvements in physicochemical properties and water solubility owing to a reduction in particle size, transformation from a crystalline to amorphous structure, and the formation of hydrogen bonds with the nanoparticle carriers. In terms of its biological actions, magnolol nanoparticles attenuated TNF-α-induced VCAM-1 protein expression, promoter activity, and mRNA expression in endothelial cells in vitro. This was found to be mediated by the ERK, AKT, and NF-κB signaling pathways. In addition, magnolol nanoparticles inhibited TNF-α-induced leukocyte adhesion to endothelial cells, and suppressed TNF-α-induced VCAM-1 expression in the aortic endothelium of mice. In summary, since magnolol nanoparticles inhibit endothelial VCAM-1 expression and leukocyte adhesion to endothelial cells, this novel drug formulation may be a potentially useful therapeutic formulation to prevent the development of atherosclerosis and inflammatory diseases.

Ferritin Decorated PLGA/Paclitaxel Loaded Nanoparticles Endowed with an Enhanced Toxicity Toward MCF-7 Breast Tumor Cells.

PubMed

Turino, Ludmila N; Ruggiero, Maria R; Stefanìa, Rachele; Cutrin, Juan C; Aime, Silvio; Geninatti Crich, Simonetta

2017-04-19

Polylactic and glycolic acid nanoparticles (PLGA-NPs), coated with L-ferritin, are exploited for the simultaneous delivery of paclitaxel and an amphiphilic Gd based MRI contrast agent into breast cancer cells (MCF7). L-ferritin has been covalently conjugated to the external surface of PLGA-NPs exploiting NHS activated carboxylic groups. The results confirmed that nanoparticles decorated with L-ferritin have many advantages with respect to both albumin-decorated and nondecorated particles. Ferritin moieties endow PLGA-NPs with targeting capability, exploiting SCARA5 receptors overexpressed by these tumor cells, that results in an increased paclitaxel cytotoxicity. Moreover, protein coating increased nanoparticle stability, thus reducing the fast and aspecific drug release before reaching the target. The theranostic potential of the nanoparticles has been demonstrated by evaluating the signal intensity enhancement on T 1 -weighted MRI images of labeled MCF7 cells. The results were compared with that obtained with MDA cells used as negative control due to their lower SCARA5 expression.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

PubMed

Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Synthesis and characterization of Fe-based metal and oxide based nanoparticles: discoveries and research highlights of potential applications in biology and medicine.

PubMed

Long, Nguyen Viet; Thi, Cao Minh; Yong, Yang; Cao, Yanqin; Wu, Haibo; Nogami, Masayuki

2014-01-01

In this review, we have presented the controlled synthesis of Fe-based metal and oxide nanoparticles with large size by chemical methods. The issues of the size, shape and morphology of Fe nanoparticles are discussed in the certain ranges of practical applications in biology and medicine. The homogeneous nanosystems of Fe-based metal and oxide nanoparticles with various sizes and shapes from the nano-to-micro ranges can be used in order to meet the demands of the treatments of dangerous tumors and cancers through magnetic hyperthermia and magnetic resonance imaging (MRI). In this context, the polyhedral Fe-based metal and oxide nanoparticles having large size in the ranges from 1000 nm to 5000 nm can be potentially used in magnetic hyperthermia and MRI in the innovative drug delivery, diagnosis, treatment, and therapy of tumor and cancer diseases because of their very high bio-adaptability. We have suggested that high stability and durability of Fe-based metal and oxide nanoparticles are very crucial to recent magnetic hyperthermia and MRI technology. The roles of various Fe-based nanostructures are focused in biomedical applications of tumors and cancers diagnostics, targeted drug delivery, and magnetic hyperthermia. Finally, Fe-based, α-, β- and γ-Fe2O3, and Fe3O4-based nanoparticles are shortly discussed in various potential applications in catalysis, biology, and medicine.

Magnetic Nanoparticles for Cancer Diagnosis and Therapy

PubMed Central

Yigit, Mehmet V.; Moore, Anna

2013-01-01

Nanotechnology is evolving as a new field that has a potentially high research and clinical impact. Medicine, in particular, could benefit from nanotechnology, due to emerging applications for noninvasive imaging and therapy. One important nanotechnological platform that has shown promise includes the so-called iron oxide nanoparticles. With specific relevance to cancer therapy, iron oxide nanoparticle-based therapy represents an important alternative to conventional chemotherapy, radiation, or surgery. Iron oxide nanoparticles are usually composed of three main components: an iron core, a polymer coating, and functional moieties. The biodegradable iron core can be designed to be superparamagnetic. This is particularly important, if the nanoparticles are to be used as a contrast agent for noninvasive magnetic resonance imaging (MRI). Surrounding the iron core is generally a polymer coating, which not only serves as a protective layer but also is a very important component for transforming nanoparticles into biomedical nanotools for in vivo applications. Finally, different moieties attached to the coating serve as targeting macromolecules, therapeutics payloads, or additional imaging tags. Despite the development of several nanoparticles for biomedical applications, we believe that iron oxide nanoparticles are still the most promising platform that can transform nanotechnology into a conventional medical discipline. PMID:22274558

High Spatiotemporal Resolution Prostate MRI

DTIC Science & Technology

2016-09-01

1 AD AWARD NUMBER: W81XWH-15-1-0341 TITLE: High Spatiotemporal Resolution Prostate MRI PRINCIPAL INVESTIGATOR: Stephen J. Riederer CONTRACTING...REPORT TYPE Annual 3. DATES COVERED 15 Aug 2015 - 14 Aug 2016 4. TITLE AND SUBTITLE High Spatiotemporal Resolution Prostate MRI 5a. CONTRACT NUMBER...improved means using MRI for detecting prostate cancer with the potential for differentiating disease aggressiveness. The hypothesis is that dynamic

Improved paramagnetic chelate for molecular imaging with MRI

NASA Astrophysics Data System (ADS)

Winter, Patrick; Athey, Phillip; Kiefer, Garry; Gulyas, Gyongyi; Frank, Keith; Fuhrhop, Ralph; Robertson, David; Wickline, Samuel; Lanza, Gregory

2005-05-01

The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto perfluorocarbon nanoparticles, i.e., gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid phosphatidylethanolamine (Gd-MeO-DOTA-PE) and gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid triglycine phosphatidylethanolamine (Gd-MeO-DOTA-triglycine-PE (Gd-MeO-DOTA-triglycine-PE)), were compared to a prototypic gadolinium-diethylene-triamine-pentaacetic acid bis-oleate (Gd-DTPA-BOA) paramagnetic formulation. Nanoparticles with MeO-DOTA-based chelates demonstrated higher relaxivity (40% higher for Gd-MeO-DOTA-PE and 55% higher for Gd-MeO-DOTA-triglycine-PE) and less transmetallation than the original Gd-DTPA-BOA-based agent.

Folate-decorated anticancer drug and magnetic nanoparticles encapsulated polymeric carrier for liver cancer therapeutics.

PubMed

Li, Yu-Ji; Dong, Ming; Kong, Fan-Min; Zhou, Jian-Ping

2015-07-15

Nanoparticulate system with theranostic applications has attracted significant attention in cancer therapeutics. In the present study, we have developed a novel composite PLGA NP co-encapsulated with anticancer drug (sorafenib) and magnetic NP (SPION). We have successfully developed nanosized folate-conjugated PEGylated PLGA nanoparticles (SRF/FA-PEG-PLGA NP) with both anticancer and magnetic resonance property. We have showed that FA-conjugated NP exhibits sustained drug release and enhanced cellular uptake in BEL7402 cancer cells. The targeted NP effectively suppressed the tumor cell proliferation and has improved the anticancer efficacy than that of free drug or non-targeted one. Additionally, enhanced MRI properties demonstrate this formulation has good imaging agent characteristics. Finally, SRF/FA-PEG-PLGA NP effectively inhibited the colony forming ability indicating its superior anticancer effect. Together, these multifunctional nanoparticles would be most ideal to improve the therapeutic response in cancer and holds great potential to be a part of future nanomedicine. Our unique approach could be extended for multiple biomedical applications. Copyright © 2015. Published by Elsevier B.V.

Well-Defined Peapod-like Magnetic Nanoparticles and Their Controlled Modification for Effective Imaging Guided Gene Therapy.

PubMed

Wang, Ranran; Hu, Yang; Zhao, Nana; Xu, Fu-Jian

2016-05-11

Due to their unique properties, one-dimensional (1D) magnetic nanostructures are of great significance for biorelated applications. A facile and straightforward strategy to fabricate 1D magnetic structure with special shapes is highly desirable. In this work, well-defined peapod-like 1D magnetic nanoparticles (Fe3O4@SiO2, p-FS) are readily synthesized by a facile method without assistance of any templates, magnetic string or magnetic field. There are few reports on 1D gene carriers based on Fe3O4 nanoparticles. BUCT-PGEA (ethanolamine-functionalized poly(glycidyl methacrylate) is subsequently grafted from the surface of p-FS nanoparticles by atom transfer radical polymerization to construct highly efficient gene vectors (p-FS-PGEA) for effective biomedical applications. Peapod-like p-FS nanoparticles were proven to largely improve gene transfection performance compared with ordinary spherical Fe3O4@SiO2 nanoparticles (s-FS). External magnetic field was also utilized to further enhance the transfection efficiency. Moreover, the as-prepared p-FS-PGEA gene carriers could combine the magnetic characteristics of p-FS to well achieve noninvasive magnetic resonance imaging (MRI). We show here novel and multifunctional magnetic nanostructures fabricated for biomedical applications that realized efficient gene delivery and real-time imaging at the same time.

Highly stable silica-coated manganese ferrite nanoparticles as high-efficacy T2 contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Ahmad, Ashfaq; Bae, Hongsub; Rhee, Ilsu

2018-05-01

Highly stable silica-coated manganese ferrite nanoparticles were fabricated for application as magnetic resonance imagining (MRI) contrast agents. The manganese ferrite nanoparticles were synthesized using a hydrothermal technique and coated with silica. The particle size was investigated using transmission electron microscopy and was found to be 40-60 nm. The presence of the silica coating on the particle surface was confirmed by Fourier transform infrared spectroscopy. The crystalline structure was investigated by X-ray diffraction, and the particles were revealed to have an inverse spinel structure. Superparamagnetism was confirmed by the magnetic hysteresis curves obtained using a vibrating sample magnetometer. The efficiency of the MRI contrast agents was investigated by using aqueous solutions of the particles in a 4.7 T MRI scanner. The T1 and T2 relaxivities of the particles were 1.42 and 60.65 s-1 mM-1, respectively, in water. The ratio r2/r1 was 48.91, confirming that the silica-coated manganese ferrite nanoparticles were suitable high-efficacy T2 contrast agents.

Engineering the defect state and reducibility of ceria based nanoparticles for improved anti-oxidation performance

NASA Astrophysics Data System (ADS)

Wang, Yan-Jie; Dong, Hao; Lyu, Guang-Ming; Zhang, Huai-Yuan; Ke, Jun; Kang, Li-Qun; Teng, Jia-Li; Sun, Ling-Dong; Si, Rui; Zhang, Jing; Liu, Yan-Jun; Zhang, Ya-Wen; Huang, Yun-Hui; Yan, Chun-Hua

2015-08-01

Due to their excellent anti-oxidation performance, CeO2 nanoparticles receive wide attention in pharmacological application. Deep understanding of the anti-oxidation mechanism of CeO2 nanoparticles is extremely important to develop potent CeO2 nanomaterials for anti-oxidation application. Here, we report a detailed study on the anti-oxidation process of CeO2 nanoparticles. The valence state and coordination structure of Ce are characterized before and after the addition of H2O2 to understand the anti-oxidation mechanism of CeO2 nanoparticles. Adsorbed peroxide species are detected during the anti-oxidation process, which are responsible for the red-shifted UV-vis absorption spectra of CeO2 nanoparticles. Furthermore, the coordination number of Ce in the first coordination shell slightly increased after the addition of H2O2. On the basis of these experimental results, the reactivity of coordination sites for peroxide species is considered to play a key role in the anti-oxidation performance of CeO2 nanoparticles. Furthermore, we present a robust method to engineer the anti-oxidation performance of CeO2 nanoparticles through the modification of the defect state and reducibility by doping with Gd3+. Improved anti-oxidation performance is also observed in cell culture, where the biocompatible CeO2-based nanoparticles can protect INS-1 cells from oxidative stress induced by H2O2, suggesting the potential application of CeO2 nanoparticles in the treatment of diabetes.Due to their excellent anti-oxidation performance, CeO2 nanoparticles receive wide attention in pharmacological application. Deep understanding of the anti-oxidation mechanism of CeO2 nanoparticles is extremely important to develop potent CeO2 nanomaterials for anti-oxidation application. Here, we report a detailed study on the anti-oxidation process of CeO2 nanoparticles. The valence state and coordination structure of Ce are characterized before and after the addition of H2O2 to understand the anti

Synthesis and characterization of bracelet-like magnetic nanorings consisting of Ag-Fe3O4 bi-component nanoparticles.

PubMed

Zhou, Shuai; Chen, Qianwang

2011-09-14

Stable bracelet-like magnetic nanorings, formed by Ag-Fe(3)O(4) nanoparticles with an average size around 40 nm, have been successfully prepared in large scale by means of reducing Ag(+) and Fe(3+) simultaneously under mild conditions. In the reaction, tiny grains of silver are used as seeds to prompt small Fe(3)O(4) nanoparticles to grow larger, which is essential to enhance the magnetic dipole-dipole interactions, while only superparamagnetic Fe(3)O(4) nanoparticles (about 10 nm in size) can be obtained in the absence of Ag seeds. The XRD, TEM, SAED and the EDS line scan data reveal that these nanoparticles are in the core-shell structure. These magnetic Ag-Fe(3)O(4) nanoparticles assembled into nanorings by magnetic dipole-dipole interactions with a diameter of 100-200 nm. The saturation magnetization of the nanorings is 39.5 emu g(-1) at room temperature. The MRI images indicate that these kind of nanorings have the potential application in diagnostics as a T(2) MRI contrast agent. This journal is © The Royal Society of Chemistry 2011

Porphyrin-based polysilsesquioxane nanoparticles to improve photodynamic therapy for cancer treatment

NASA Astrophysics Data System (ADS)

Vivero-Escoto, Juan L.; DeCillis, Daniel; Fritts, Laura; Vega, Daniel L.

2014-03-01

Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer treatment. The photosensitizer (PS) is perhaps the most critical component of PDT, and continues to be an area of intense scientific research. Traditionally, PS molecules (e.g. porphyrins) have dominated the field. Nevertheless, these PS agents have several disadvantages, with low water solubility, poor light absorption and reduced selectivity for targeted tissues being some of the main drawbacks. Polysilsesquioxane (PSilQ) nanoparticles are crosslinked homopolymers formed by the condensation of functionalized trialkoxysilanes or bis(trialkoxysilanes). We believe that PSilQ particles provide an interesting platform for developing PS nanocarriers. Several advantages can be foreseen by using this platform such as carrying a large payload of PS molecules; their surface and composition can be tailored to develop multifunctional systems (e.g. target-specific); and due to their small size, nanoparticles can penetrate deep into tissues and be readily internalized by cells. In this work, PSilQ nanoparticles with a high payload of photosensitizers were synthesized, characterized, and applied in vitro. The network of this nanomaterial is formed by protoporphyrin IX (PpIX) molecules chemically connected via a redox-responsive linker. Under reducing environment such as the one found in cancer cells the nanoparticles can be degraded to efficiently release single photosensitizers in the cytoplasm. The phototoxicity of this porphyrin-based PSilQ nanomaterial was successfully demonstrated in vitro using human cervical (HeLa) cancer cells. We envision that this platform can be further functionalized with polyethylene glycol (PEG) and targeting ligands to improve its biocompatibility and target specificity.

High-throughput fabrication and screening improves gold nanoparticle chemiresistor sensor performance.

PubMed

Hubble, Lee J; Cooper, James S; Sosa-Pintos, Andrea; Kiiveri, Harri; Chow, Edith; Webster, Melissa S; Wieczorek, Lech; Raguse, Burkhard

2015-02-09

Chemiresistor sensor arrays are a promising technology to replace current laboratory-based analysis instrumentation, with the advantage of facile integration into portable, low-cost devices for in-field use. To increase the performance of chemiresistor sensor arrays a high-throughput fabrication and screening methodology was developed to assess different organothiol-functionalized gold nanoparticle chemiresistors. This high-throughput fabrication and testing methodology was implemented to screen a library consisting of 132 different organothiol compounds as capping agents for functionalized gold nanoparticle chemiresistor sensors. The methodology utilized an automated liquid handling workstation for the in situ functionalization of gold nanoparticle films and subsequent automated analyte testing of sensor arrays using a flow-injection analysis system. To test the methodology we focused on the discrimination and quantitation of benzene, toluene, ethylbenzene, p-xylene, and naphthalene (BTEXN) mixtures in water at low microgram per liter concentration levels. The high-throughput methodology identified a sensor array configuration consisting of a subset of organothiol-functionalized chemiresistors which in combination with random forests analysis was able to predict individual analyte concentrations with overall root-mean-square errors ranging between 8-17 μg/L for mixtures of BTEXN in water at the 100 μg/L concentration. The ability to use a simple sensor array system to quantitate BTEXN mixtures in water at the low μg/L concentration range has direct and significant implications to future environmental monitoring and reporting strategies. In addition, these results demonstrate the advantages of high-throughput screening to improve the performance of gold nanoparticle based chemiresistors for both new and existing applications.

Exploring Reaction Conditions to Improve the Magnetic Response of Cobalt-Doped Ferrite Nanoparticles

PubMed Central

Galarreta, Itziar; Gil de Muro, Izaskun; Lezama, Luis

2018-01-01

With the aim of studying the influence of synthesis parameters in structural and magnetic properties of cobalt-doped magnetite nanoparticles, Fe3−xCoxO4 (0 < x < 0.15) samples were synthetized by thermal decomposition method at different reaction times (30–120 min). The Co ferrite nanoparticles are monodisperse with diameters between 6 and 11 nm and morphologies depending on reaction times, varying from spheric, cuboctahedral, to cubic. Chemical analysis and X-ray diffraction were used to confirm the composition, high crystallinity, and pure-phase structure. The investigation of the magnetic properties, both magnetization and electronic magnetic resonance, has led the conditions to improve the magnetic response of doped nanoparticles. Magnetization values of 86 emu·g−1 at room temperature (R.T.) have been obtained for the sample with the highest Co content and the highest reflux time. Magnetic characterization also displays a dependence of the magnetic anisotropy constant with the varying cobalt content. PMID:29370104

Sodium MRI: Methods and applications

PubMed Central

Madelin, Guillaume; Lee, Jae-Seung; Regatte, Ravinder R.; Jerschow, Alexej

2014-01-01

Sodium NMR spectroscopy and MRI have become popular in recent years through the increased availability of high-field MRI scanners, advanced scanner hardware and improved methodology. Sodium MRI is being evaluated for stroke and tumor detection, for breast cancer studies, and for the assessment of osteoarthritis and muscle and kidney functions, to name just a few. In this article, we aim to present an up-to-date review of the theoretical background, the methodology, the challenges and limitations, and current and potential new applications of sodium MRI. PMID:24815363

Cellular transfer of magnetic nanoparticles via cell microvesicles: impact on cell tracking by magnetic resonance imaging.

PubMed

Silva, Amanda K Andriola; Wilhelm, Claire; Kolosnjaj-Tabi, Jelena; Luciani, Nathalie; Gazeau, Florence

2012-05-01

Cell labeling with magnetic nanoparticles can be used to monitor the fate of transplanted cells in vivo by magnetic resonance imaging. However, nanoparticles initially internalized in administered cells might end up in other cells of the host organism. We investigated a mechanism of intercellular cross-transfer of magnetic nanoparticles to different types of recipient cells via cell microvesicles released under cellular stress. Three cell types (mesenchymal stem cells, endothelial cells and macrophages) were labeled with 8-nm iron oxide nanoparticles. Then cells underwent starvation stress, during which they produced microvesicles that were subsequently transferred to unlabeled recipient cells. The analysis of the magnetophoretic mobility of donor cells indicated that magnetic load was partially lost under cell stress. Microvesicles shed by stressed cells participated in the release of magnetic label. Moreover, such microvesicles were uptaken by naïve cells, resulting in cellular redistribution of nanoparticles. Iron load of recipient cells allowed their detection by MRI. Cell microvesicles released under stress may be disseminated throughout the organism, where they can be uptaken by host cells. The transferred cargo may be sufficient to allow MRI detection of these secondarily labeled cells, leading to misinterpretations of the effectiveness of transplanted cells.

Combining Perfluorocarbon and Superparamagnetic Iron-oxide Cell Labeling for Improved and Expanded Applications of Cellular MRI

PubMed Central

Hitchens, T. Kevin; Liu, Li; Foley, Lesley M.; Simplaceanu, Virgil; Ahrens, Eric T.; Ho, Chien

2014-01-01

Purpose The ability to detect the migration of cells in living organisms is fundamental in understanding biological processes and important for the development of novel cell-based therapies to treat disease. MRI can be used to detect the migration of cells labeled with superparamagnetic iron-oxide (SPIO) or perfluorocarbon (PFC) agents. In this study, we explored combining these two cell-labeling approaches to overcome current limitations and enable new applications for cellular MRI. Methods We characterized 19F-NMR relaxation properties of PFC-labeled cells in the presence of SPIO and imaged cells both ex vivo and in vivo in a rodent inflammation model to demonstrate selective visualization of cell populations. Results We show that with UTE3D, RARE and FLASH 19F images one can uniquely identify PFC-labeled cells, co-localized PFC- and SPIO-labeled cells, and PFC/SPIO co-labeled cells. Conclusion This new methodology has the ability to improve and expand applications of MRI cell tracking. Combining PFC and SPIO strategies can potentially provide a method to quench PFC signal transferred from dead cells to macrophages, thereby eliminating false positives. In addition, combining these techniques could also be used to track two cell types simultaneously and probe cell-cell proximity in vivo with MRI. PMID:24478194

Water-soluble core/shell nanoparticles for proton therapy through particle-induced radiation

NASA Astrophysics Data System (ADS)

Park, Jeong Chan; Jung, Myung-Hwan; Kim, Maeng Jun; Kim, Kye-Ryung

2015-02-01

Metallic nanoparticles have been used in biomedical applications such as magnetic resonance imaging (MRI), therapy, and drug delivery systems. Metallic nanoparticles as therapeutic tools have been demonstrated using radio-frequency magnetic fields or near-infrared light. Recently, therapeutic applications of metallic nanomaterials combined with proton beams have been reported. Particle-induced radiation from metallic nanoparticles, which can enhance the therapeutic effects of proton therapy, was released when the nanoparticles were bombarded by a high-energy proton beam. Core/shell nanoparticles, especially Au-coated magnetic nanoparticles, have drawn attention in biological applications due to their attractive characteristics. However, studies on the phase transfer of organic-ligand-based core/shell nanoparticles into water are limited. Herein, we demonstrated that hydrophobic core/shell structured nanomaterials could be successfully dispersed in water through chloroform/surfactant mixtures. The effects of the core/shell nanomaterials and the proton irradiation on Escherichia coli (E. coli) were also explored.

Preliminary study of copper oxide nanoparticles acoustic and magnetic properties for medical imaging

NASA Astrophysics Data System (ADS)

Perlman, Or; Weitz, Iris S.; Azhari, Haim

2015-03-01

The implementation of multimodal imaging in medicine is highly beneficial as different physical properties may provide complementary information, augmented detection ability, and diagnosis verification. Nanoparticles have been recently used as contrast agents for various imaging modalities. Their significant advantage over conventional large-scale contrast agents is the ability of detection at early stages of the disease, being less prone to obstacles on their path to the target region, and possible conjunction to therapeutics. Copper ions play essential role in human health. They are used as a cofactor for multiple key enzymes involved in various fundamental biochemistry processes. Extremely small size copper oxide nanoparticles (CuO-NPs) are readily soluble in water with high colloidal stability yielding high bioavailability. The goal of this study was to examine the magnetic and acoustic characteristics of CuO-NPs in order to evaluate their potential to serve as contrast imaging agent for both MRI and ultrasound. CuO-NPs 7nm in diameter were synthesized by hot solution method. The particles were scanned using a 9.4T MRI and demonstrated a concentration dependent T1 relaxation time shortening phenomenon. In addition, it was revealed that CuO-NPs can be detected using the ultrasonic B-scan imaging. Finally, speed of sound based ultrasonic computed tomography was applied and showed that CuO-NPs can be clearly imaged. In conclusion, the preliminary results obtained, positively indicate that CuO-NPs may be imaged by both MRI and ultrasound. The results motivate additional in-vivo studies, in which the clinical utility of fused images derived from both modalities for diagnosis improvement will be studied.

Maghemite Nanoparticles Acts as Nanozymes, Improving Growth and Abiotic Stress Tolerance in Brassica napus

NASA Astrophysics Data System (ADS)

Palmqvist, N. G. Martin; Seisenbaeva, Gulaim A.; Svedlindh, Peter; Kessler, Vadim G.

2017-12-01

Yttrium doping-stabilized γ-Fe2O3 nanoparticles were studied for its potential to serve as a plant fertilizer and, through enzymatic activity, support drought stress management. Levels of both hydrogen peroxide and lipid peroxidation, after drought, were reduced when γ-Fe2O3 nanoparticles were delivered by irrigation in a nutrient solution to Brassica napus plants grown in soil. Hydrogen peroxide was reduced from 151 to 83 μM g-1 compared to control, and the malondialdehyde formation was reduced from 36 to 26 mM g-1. Growth rate of leaves was enhanced from 33 to 50% growth compared to fully fertilized plants and SPAD-measurements of chlorophyll increased from 47 to 52 suggesting improved agronomic properties by use of γ-Fe2O3 nanoparticles as fertilizer as compared to chelated iron.

Pulsed Laser Synthesized Magnetic Cobalt Oxide Nanoparticles for Biomedical Applications

NASA Astrophysics Data System (ADS)

Bhatta, Hari; Gupta, Ram; Ghosh, Kartik; Kahol, Pawan; Delong, Robert; Wanekawa, Adam

2011-03-01

Nanomaterials research has become a major attraction in the field of advanced materials research in the area of Physics, Chemistry, and Materials Science. Biocompatible and chemically stable magnetic metal oxide nanoparticles have biomedical applications that includes drug delivery, cell and DNA separation, gene cloning, magnetic resonance imaging (MRI). This research is aimed at the fabrication of magnetic cobalt oxide nanoparticles using a safe, cost effective, and easy to handle technique that is capable of producing nanoparticles free of any contamination. Cobalt oxide nanoparticles have been synthesized at room temperature using cobalt foil by pulsed laser ablation technique. These cobalt oxide nanoparticles were characterized using UV-Visible (UV-Vis) spectroscopy, transmission electron microscopy (TEM), and dynamic laser light scattering (DLLS). The magnetic cobalt oxides nanoparticles were stabilized in glucose solutions of various concentrations in deionized water. The presence of UV-Vis absorption peak at 270 nm validates the nature of cobalt oxide nanoparticles. The DLLS size distributions of nanoparticles are in the range of 110 to 300 nm, which further confirms the presence nanoparticles. This work is partially supported by National Science Foundation (DMR- 0907037).

Feasibility study of Fe3O4/TaO x nanoparticles as a radiosensitizer for proton therapy

NASA Astrophysics Data System (ADS)

Ahn, Sang Hee; Lee, Nohyun; Choi, Changhoon; Shin, Sung Won; Han, Youngyih; Park, Hee Chul

2018-06-01

We investigated the feasibility of using multifunctional Fe3O4/TaO x (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe3O4/TaO x nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg kg‑1 of 19 nm-diameter Fe3O4/TaO x nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe3O4/TaO x nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150 MeV proton beams irradiated x-ray contrast agent (iodine, BaSO4), MRI contrast agent (gadolinium, Fe3O4), Au, Fe3O4/TaO x (core/shell) nanoparticles and water located at the centre of a 4  ×  4  ×  4 µm3 water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70 MeV protons irradiated the Au, gadolinium, Fe3O4/TaO x , Fe3O4, iodine, and BaSO4 nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe3O4/TaO x nanoparticles have the potential to be used as a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe3O4/TaO x was half that with Au. However, Fe3O4/TaO x is

New oil-in-water magnetic emulsion as contrast agent for in vivo magnetic resonance imaging (MRI).

PubMed

Ahmed, Naveed; Jaafar-Maalej, Chiraz; Eissa, Mohamed Mahmoud; Fessi, Hatem; Elaissari, Abdelhamid

2013-09-01

Nowadays, bio-imaging techniques are widely applied for the diagnosis of various diseased/tumoral tissues in the body using different contrast agents. Accordingly, the advancement in bionanotechnology research is enhanced in this regard. Among contrast agents used, superparamagnetic iron oxide nanoparticles were developed by many researchers and applied for in vive magnetic resonance imaging (MRI). In this study, a new oil-in-water magnetic emulsion was used as contrast agent in MRI, after being characterized in terms of particle size, iron oxide content, magnetic properties and colloidal stability using dynamic light scattering (DLS), thermal gravimetric analysis (TGA), vibrating sample magnetometer (VSM) and zeta potential measurement techniques, respectively. The hydrodynamic size and magnetic content of the magnetic colloidal particles were found to be 250 nm and 75 wt%, respectively. In addition, the used magnetic emulsion possesses superparamagentic properties and high colloidal stability in aqueous medium. Then, the magnetic emulsion was highly diluted and administered intravenously to the Sprague dawley rats to be tested as contrast agent for in vivo MRI. In this preliminary study, MRI images showed significant enhancement in contrast, especially for T2 (relaxation time) contrast enhancement, indicating the distribution of magnetic colloidal nanoparticles within organs, like liver, spleen and kidneys of the Sprague dawley rats. In addition, it was found that 500 microL of the highly diluted magnetic emulsion (0.05 wt%) was found adequate for MRI analysis. This seems to be useful for further investigations especially in theranostic applications of magnetic emulsion.

R1 dispersion contrast at high field with fast field-cycling MRI.

PubMed

Bödenler, Markus; Basini, Martina; Casula, Maria Francesca; Umut, Evrim; Gösweiner, Christian; Petrovic, Andreas; Kruk, Danuta; Scharfetter, Hermann

2018-05-01

Contrast agents with a strong R 1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R 1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B 0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R 1 dispersion imaging and demonstrate the capability of generating R 1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R 1 dispersion at a field strength of 3 T. Copyright © 2018 Elsevier Inc. All rights reserved.

Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

NASA Astrophysics Data System (ADS)

Ma, J.; Chen, K.

2016-04-01

Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

MRI-visible liposome nanovehicles for potential tumor-targeted delivery of multimodal therapies

NASA Astrophysics Data System (ADS)

Ren, Lili; Chen, Shizhen; Li, Haidong; Zhang, Zhiying; Ye, Chaohui; Liu, Maili; Zhou, Xin

2015-07-01

Real-time diagnosis and monitoring of disease development, and therapeutic responses to treatment, are possible by theranostic magnetic resonance imaging (MRI). Here we report the synthesis of a multifunctional liposome, which contains Gd-DOTA (an MRI probe), paclitaxel and c(RGDyk) (a targeted peptide). This nanoparticle overcame the insolubility of paclitaxel, reduced the side effects of FDA-approved formulation of PTX-Cre (Taxol®) and improved drug delivery efficiency to the tumor. c(RGDyk) modification greatly enhanced the cytotoxicity of the drug in tumor cells A549. The T1 relaxivity in tumor cells treated with the targeted liposome formulation was increased 16-fold when compared with the non-targeted group. In vivo, the tumors in mice were visualized using T1-weighted imaging after administration of the liposome. Also the tumor growth could be inhibited well after the treatment. Fluorescence images in vitro and ex vivo also showed the targeting effect of this liposome in tumor cells, indicating that this nanovehicle could limit the off-target side effects of anticancer drugs and contrast agents. These findings lay the foundation for further tumor inhibition study and application of this delivery vehicle in cancer therapy settings.

Mesoporous silica nanoparticles functionalized with fluorescent and MRI reporters for the visualization of murine tumors overexpressing αvβ3 receptors

NASA Astrophysics Data System (ADS)

Hu, He; Arena, Francesca; Gianolio, Eliana; Boffa, Cinzia; di Gregorio, Enza; Stefania, Rachele; Orio, Laura; Baroni, Simona; Aime, Silvio

2016-03-01

A novel fluorescein/Gd-DOTAGA containing nanoprobe for the visualization of tumors by optical and Magnetic Resonance Imaging (MRI) is reported herein. It is based on the functionalization of the surface of small mesoporous silica nanoparticles (MSNs) (~30 nm) with the arginine-glycine-aspartic (RGD) moieties, which are known to target αvβ3 integrin receptors overexpressed in several tumor cells. The obtained nanoprobe (Gd-MSNs-RGD) displays good stability, tolerability and high relaxivity (37.6 mM-1 s-1 at 21.5 MHz). After a preliminary evaluation of their cytotoxicity and targeting capability toward U87MG cells by in vitro fluorescence and MR imaging, the nanoprobes were tested in vivo by T1-weighted MR imaging of xenografted murine tumor models. The obtained results demonstrated that the Gd-MSNs-RGD nanoprobes are good reporters both in vitro and in vivo for the MR-visualization of tumor cells overexpressing αvβ3 integrin receptors.A novel fluorescein/Gd-DOTAGA containing nanoprobe for the visualization of tumors by optical and Magnetic Resonance Imaging (MRI) is reported herein. It is based on the functionalization of the surface of small mesoporous silica nanoparticles (MSNs) (~30 nm) with the arginine-glycine-aspartic (RGD) moieties, which are known to target αvβ3 integrin receptors overexpressed in several tumor cells. The obtained nanoprobe (Gd-MSNs-RGD) displays good stability, tolerability and high relaxivity (37.6 mM-1 s-1 at 21.5 MHz). After a preliminary evaluation of their cytotoxicity and targeting capability toward U87MG cells by in vitro fluorescence and MR imaging, the nanoprobes were tested in vivo by T1-weighted MR imaging of xenografted murine tumor models. The obtained results demonstrated that the Gd-MSNs-RGD nanoprobes are good reporters both in vitro and in vivo for the MR-visualization of tumor cells overexpressing αvβ3 integrin receptors. Electronic supplementary information (ESI) available: Absorption and emission spectra, energy

Improved accuracy and precision of tracer kinetic parameters by joint fitting to variable flip angle and dynamic contrast enhanced MRI data.

PubMed

Dickie, Ben R; Banerji, Anita; Kershaw, Lucy E; McPartlin, Andrew; Choudhury, Ananya; West, Catharine M; Rose, Chris J

2016-10-01

To improve the accuracy and precision of tracer kinetic model parameter estimates for use in dynamic contrast enhanced (DCE) MRI studies of solid tumors. Quantitative DCE-MRI requires an estimate of precontrast T1 , which is obtained prior to fitting a tracer kinetic model. As T1 mapping and tracer kinetic signal models are both a function of precontrast T1 it was hypothesized that its joint estimation would improve the accuracy and precision of both precontrast T1 and tracer kinetic model parameters. Accuracy and/or precision of two-compartment exchange model (2CXM) parameters were evaluated for standard and joint fitting methods in well-controlled synthetic data and for 36 bladder cancer patients. Methods were compared under a number of experimental conditions. In synthetic data, joint estimation led to statistically significant improvements in the accuracy of estimated parameters in 30 of 42 conditions (improvements between 1.8% and 49%). Reduced accuracy was observed in 7 of the remaining 12 conditions. Significant improvements in precision were observed in 35 of 42 conditions (between 4.7% and 50%). In clinical data, significant improvements in precision were observed in 18 of 21 conditions (between 4.6% and 38%). Accuracy and precision of DCE-MRI parameter estimates are improved when signal models are fit jointly rather than sequentially. Magn Reson Med 76:1270-1281, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Dendrimer-based nanoparticles for cancer therapy.

PubMed

Baker, James R

2009-01-01

Recent work has suggested that nanoparticles in the form of dendrimers may be a keystone in the future of therapeutics. The field of oncology could soon be revolutionized by novel strategies for diagnosis and therapy employing dendrimer-based nanotherapeutics. Several aspects of cancer therapy would be involved. Diagnosis using imaging techniques such as MRI will be improved by the incorporation of dendrimers as advanced contrast agents. This might involve novel contrast agents targeted specifically to cancer cells. Dendrimers can also be being applied to a variety of cancer therapies to improve their safety and efficacy. A strategy, somewhat akin to the "Trojan horse," involves targeting anti-metabolite drugs via vitamins or hormones that tumors need for growth. Further applications of dendrimers in photodynamic therapy, boron neutron capture therapy, and gene therapy for cancer are being examined. This presentation will cover the fundamentals of research utilizing dendrimers for cancer diagnosis and therapy. An evaluation of this new technologies will detail what advantage dendrimer based therapeutics might have over conventional cancer drugs.

Diblock-copolymer-mediated self-assembly of protein-stabilized iron oxide nanoparticle clusters for magnetic resonance imaging.

PubMed

Tähkä, Sari; Laiho, Ari; Kostiainen, Mauri A

2014-03-03

Superparamagnetic iron oxide nanoparticles (SPIONs) can be used as efficient transverse relaxivity (T2 ) contrast agents in magnetic resonance imaging (MRI). Organizing small (D<10 nm) SPIONs into large assemblies can considerably enhance their relaxivity. However, this assembly process is difficult to control and can easily result in unwanted aggregation and precipitation, which might further lead to lower contrast agent performance. Herein, we present highly stable protein-polymer double-stabilized SPIONs for improving contrast in MRI. We used a cationic-neutral double hydrophilic poly(N-methyl-2-vinyl pyridinium iodide-block-poly(ethylene oxide) diblock copolymer (P2QVP-b-PEO) to mediate the self-assembly of protein-cage-encapsulated iron oxide (γ-Fe2 O3 ) nanoparticles (magnetoferritin) into stable PEO-coated clusters. This approach relies on electrostatic interactions between the cationic N-methyl-2-vinylpyridinium iodide block and magnetoferritin protein cage surface (pI≈4.5) to form a dense core, whereas the neutral ethylene oxide block provides a stabilizing biocompatible shell. Formation of the complexes was studied in aqueous solvent medium with dynamic light scattering (DLS) and cryogenic transmission electron microcopy (cryo-TEM). DLS results indicated that the hydrodynamic diameter (Dh ) of the clusters is approximately 200 nm, and cryo-TEM showed that the clusters have an anisotropic stringlike morphology. MRI studies showed that in the clusters the longitudinal relaxivity (r1 ) is decreased and the transverse relaxivity (r2 ) is increased relative to free magnetoferritin (MF), thus indicating that clusters can provide considerable contrast enhancement. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Whole body MRI: Improved Lesion Detection and Characterization With Diffusion Weighted Techniques

PubMed Central

Attariwala, Rajpaul; Picker, Wayne

2013-01-01

Diffusion-weighted imaging (DWI) is an established functional imaging technique that interrogates the delicate balance of water movement at the cellular level. Technological advances enable this technique to be applied to whole-body MRI. Theory, b-value selection, common artifacts and target to background for optimized viewing will be reviewed for applications in the neck, chest, abdomen, and pelvis. Whole-body imaging with DWI allows novel applications of MRI to aid in evaluation of conditions such as multiple myeloma, lymphoma, and skeletal metastases, while the quantitative nature of this technique permits evaluation of response to therapy. Persisting signal at high b-values from restricted hypercellular tissue and viscous fluid also permits applications of DWI beyond oncologic imaging. DWI, when used in conjunction with routine imaging, can assist in detecting hemorrhagic degradation products, infection/abscess, and inflammation in colitis, while aiding with discrimination of free fluid and empyema, while limiting the need for intravenous contrast. DWI in conjunction with routine anatomic images provides a platform to improve lesion detection and characterization with findings rivaling other combined anatomic and functional imaging techniques, with the added benefit of no ionizing radiation. PMID:23960006

A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

PubMed

Khachaturian, Mark Haig

2010-01-01

Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments

PubMed Central

Khachaturian, Mark Haig

2010-01-01

Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4–8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic). PMID:21243106

Synthesis of hydrophilic superparamagnetic magnetite nanoparticles via thermal decomposition of Fe(acac), in 80 vol% TREG + 20 vol% TREM.

PubMed

Maityt, Dipak; Pradhan, Pallab; Chandrasekharan, Prashant; Kale, S N; Shuter, Borys; Bahadur, Dhirendra; Feng, Si-Shen; Xue, Jun-Min; Ding, Jun

2011-03-01

In this paper, we report single step synthesis of hydrophilic superparamagnetic magnetite nanoparticles by thermolysis of Fe(acac)3 and their characterization of the properties relevant to biomedical applications like hyperthermia and magnetic resonance imaging (MRI). Size and morphology of the particles were determined by Transmission electron microscopy (TEM) while phase purity and structure of the particles were identified by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Magnetic properties were evaluated using vibrating sample magnetometer (VSM) and superconducting quantum interference device (SQUID) measurements. The as prepared nanoparticles were found to be superparamagnetic with the blocking temperature of 136 K and were easily suspendable in water. Cytotoxicity studies on human cervical (SiHa), mouse melanoma (B16F10) and mouse primary fibroblast cells demonstrated that up to a dose of 0.1 mg/ml, the magnetite nanoparticles were nontoxic to the cells. To evaluate the feasibility of their uses in hyperthermia and MRI applications, specific absorption rate (SAR) and spin-spin relaxation time (T2) were measured respectively. SAR has been calculated to be above 80 Watt/g for samples with the iron concentration of 5-20 mg/ml at 10 kA/m AC magnetic field and 425 kHz frequency. r2 relaxivity value was measured as 358.4 mM(-1)S(-1) which is almost double as compared to that of the Resovist, a commercially available MRI contrast agent. Thus the as-prepared magnetite nanoparticles may be used for hyperthermia and MRI applications due to their promising SAR and r2 values.

Magnetic Nanoparticles for Multi-Imaging and Drug Delivery

PubMed Central

Lee, Jae-Hyun; Kim, Ji-wook; Cheon, Jinwoo

2013-01-01

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed. PMID:23579479

Silica-F127 nanohybrid-encapsulated manganese oxide nanoparticles for optimized T1 magnetic resonance relaxivity

NASA Astrophysics Data System (ADS)

Wei Hsu, Benedict You; Wang, Miao; Zhang, Yu; Vijayaragavan, Vimalan; Wong, Siew Yee; Yuang-Chi Chang, Alex; Bhakoo, Kishore Kumar; Li, Xu; Wang, John

2013-12-01

To properly engineer MnO nanoparticles (MONPs) of high r1 relaxivity, a nanohybrid coating consisting of silica and F127 (PEO106PPO70PEO106) is designed to encapsulate MONPs. Achieved by an interfacial templating scheme, the nanohybrid encapsulating layer is highly permeable and hydrophilic to allow for an optimal access of water molecules to the encapsulated manganese oxide core. Hence, the efficacy of MONPs as MRI contrast agents is significantly improved, as demonstrated by an enhancement of the MR signal measured with a pre-clinical 7.0 T MRI scanner. The nanohybrid encapsulation strategy also confers high colloidal stability to the hydrophobic MONPs by the surface decoration of PEO chains and a small overall diameter (<100 nm) of the PEO-SiO2 nanohybrid-encapsulated MONPs (PEOMSNs). The PEOMSNs are not susceptible to Mn-ion leaching, and their biocompatibility is affirmed by a low toxicity profile. Moreover, these hybrid nanocapsules exhibit a nano-rattle structure, which would favor the facile loading of various therapeutic reagents for theranostic applications.To properly engineer MnO nanoparticles (MONPs) of high r1 relaxivity, a nanohybrid coating consisting of silica and F127 (PEO106PPO70PEO106) is designed to encapsulate MONPs. Achieved by an interfacial templating scheme, the nanohybrid encapsulating layer is highly permeable and hydrophilic to allow for an optimal access of water molecules to the encapsulated manganese oxide core. Hence, the efficacy of MONPs as MRI contrast agents is significantly improved, as demonstrated by an enhancement of the MR signal measured with a pre-clinical 7.0 T MRI scanner. The nanohybrid encapsulation strategy also confers high colloidal stability to the hydrophobic MONPs by the surface decoration of PEO chains and a small overall diameter (<100 nm) of the PEO-SiO2 nanohybrid-encapsulated MONPs (PEOMSNs). The PEOMSNs are not susceptible to Mn-ion leaching, and their biocompatibility is affirmed by a low toxicity profile

Synthesis of internally functionalized silica nanoparticles for theranostic applications

NASA Astrophysics Data System (ADS)

Walton, Nathan Isaac

This thesis addresses the synthesis and characterization of novel inorganic silica nanoparticle hybrids. It focuses in large part on their potential applications in the medical field. Silica acts as a useful carrier for a variety of compounds and this thesis silica will demonstrate its use as a carrier for boron or gadolinium. Boron-10 and gadolinium-157 have been suggested for the radiological treatment of tumor cells through the process called neutron capture therapy (NCT). Gadolinium is also commonly used as a Magnetic Resonance Imaging (MRI) contrast agent. Particles that carry it have potential theranostic applications of both imaging and treating tumors. Chapter 1 presents a background on synthetic strategies and usages of silica nanoparticles, and NCT theory. Chapter 2 describes a procedure to create mesoporous metal chelating silica nanoparticles, mDTTA. This is achieved via a co-condensation of tetraethoxysilane (TEOS) and 3-trimethoxysilyl-propyl diethylenetriamine (SiDETA) followed by a post-synthesis modification step with bromoacetic acid (BrAA). These particles have a large surface area and well-defined pores of ~2 nm. The mDTTA nanoparticles were used to chelate the copper(II), cobalt(II) and gadolinium(III). The chelating of gadolinium is the most interesting since it can be used as a MRI contrast agent and a neutron capture therapeutic. The synthetic procedure developed also allows for the attachment of a fluorophore that gives the gadolinium chelating mDTTA nanoparticles a dual imaging modality. Chapter 3 presents the synthetic method used to produce two classes of large surface area organically modified silica (ORMOSIL) nanoparticles. Condensating the organosilane vinyltrimethoxysilane in a micellar solution results in nanoparticles that are either surface rough (raspberry-like) or mesoporous nanoparticles, which prior to this thesis has not been demonstrated in ORMOSIL chemistry. Furthermore, the vinyl functionalities are modified, using

Formic acid electrooxidation on thallium-decorated shape-controlled platinum nanoparticles: an improvement in electrocatalytic activity.

PubMed

Busó-Rogero, Carlos; Perales-Rondón, Juan V; Farias, Manuel J S; Vidal-Iglesias, Francisco J; Solla-Gullon, Jose; Herrero, Enrique; Feliu, Juan M

2014-07-21

Thallium modified shape-controlled Pt nanoparticles were prepared and their electrocatalytic activity towards formic acid electrooxidation was evaluated in 0.5 M sulfuric acid. The electrochemical and in situ FTIR spectroscopic results show a remarkable improvement in the electrocatalytic activity, especially in the low potential region (around 0.1-0.2 V vs. RHE). Cubic Pt nanoparticles modified with Tl were found to be more active than the octahedral Pt ones in the entire range of Tl coverages and potential windows. In situ FTIR spectra indicate that the promotional effect produced by Tl results in the inhibition of the poisoning step leading to COads, thus improving the onset potential for the complete formic acid oxidation to CO2. Chronoamperometric experiments were also performed at 0.2 V to evaluate the stability of the electrocatalysts at constant potential. Finally, experiments with different concentrations of formic acid (0.05-1 M) were also carried out. In all cases, Tl-modified cubic Pt nanoparticles result to be the most active. All these facts reinforce the importance of controlling the surface structure of the electrocatalysts to optimize their electrocatalytic properties.

Ascorbic acid prevents cellular uptake and improves biocompatibility of chitosan nanoparticles.

PubMed

Elshoky, Hisham A; Salaheldin, Taher A; Ali, Maha A; Gaber, Mohamed H

2018-04-11

Chitosan nanoparticles have many applications, such as gene and drug delivery, due to their biocompatibility. Chitosan nanoparticles are currently produced by dissolution in acetic acid that affects the biocompatibility at acidic pH. Here, we synthesized and characterized chitosan (CS) and ascorbate chitosan (AsCS) nanoparticles and investigated their cytotoxic effects, internalization, and distribution in the human colon carcinoma cell line using confocal laser scanning microscopy (CLSM). The CS and AsCS nanoparticles were spherical with average particle sizes of 44±8.4nm and 87±13.6nm, respectively. CS nanoparticles were taken up by the cells and showed dose-dependent cytotoxicity. By contrast, AsCS nanoparticles were not internalized and showed no cytotoxicity. Therefore, AsCS nanoparticles are more biocompatible than CS nanoparticles and may be more suitable for extracellular drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

MRI-powered biomedical devices.

PubMed

Hovet, Sierra; Ren, Hongliang; Xu, Sheng; Wood, Bradford; Tokuda, Junichi; Tse, Zion Tsz Ho

2017-11-16

Magnetic resonance imaging (MRI) is beneficial for imaging-guided procedures because it provides higher resolution images and better soft tissue contrast than computed tomography (CT), ultrasound, and X-ray. MRI can be used to streamline diagnostics and treatment because it does not require patients to be repositioned between scans of different areas of the body. It is even possible to use MRI to visualize, power, and control medical devices inside the human body to access remote locations and perform minimally invasive procedures. Therefore, MR conditional medical devices have the potential to improve a wide variety of medical procedures; this potential is explored in terms of practical considerations pertaining to clinical applications and the MRI environment. Recent advancements in this field are introduced with a review of clinically relevant research in the areas of interventional tools, endovascular microbots, and closed-loop controlled MRI robots. Challenges related to technology and clinical feasibility are discussed, including MRI based propulsion and control, navigation of medical devices through the human body, clinical adoptability, and regulatory issues. The development of MRI-powered medical devices is an emerging field, but the potential clinical impact of these devices is promising.

Improving the Performance of Heat Insulation Polyurethane Foams by Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Nikje, M. M. Alavi; Garmarudi, A. Bagheri; Haghshenas, M.; Mazaheri, Z.

Heat insulation polyurethane foam materials were doped by silica nano particles, to investigate the probable improving effects. In order to achieve the best dispersion condition and compatibility of silica nanoparticles in the polymer matrix a modification step was performed by 3-aminopropyltriethoxysilane (APTS) as coupling agent. Then, thermal and mechanical properties of polyurethane rigid foam were investigated. Thermal and mechanical properties were studied by tensile machine, thermogravimetric analysis and dynamic mechanical analysis.

Europium-engineered iron oxide nanocubes with high T1 and T2 contrast abilities for MRI in living subjects

NASA Astrophysics Data System (ADS)

Yang, Lijiao; Zhou, Zijian; Liu, Hanyu; Wu, Changqiang; Zhang, Hui; Huang, Guoming; Ai, Hua; Gao, Jinhao

2015-04-01

Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver

In situ formation of magnetopolymersomes via electroporation for MRI

NASA Astrophysics Data System (ADS)

Bain, Jennifer; Ruiz-Pérez, Lorena; Kennerley, Aneurin J.; Muench, Stephen P.; Thompson, Rebecca; Battaglia, Giuseppe; Staniland, Sarah S.

2015-09-01

As the development of diagnostic/therapeutic (and combined: theranostic) nanomedicine grows, smart drug-delivery vehicles become ever more critical. Currently therapies consist of drugs tethered to, or encapsulated within nanoparticles or vesicles. There is growing interest in functionalising them with magnetic nanoparticles (MNPs) to target the therapeutics by localising them using magnetic fields. An alternating magnetic field induces remote heating of the particles (hyperthermia) triggering drug release or cell death. Furthermore, MNPs are diagnostic MRI contrast agents. There is considerable interest in MNP embedded vehicles for nanomedicine, but their development is hindered by difficulties producing consistently monodisperse MNPs and their reliable loading into vesicles. Furthermore, it is highly advantageous to "trigger" MNP production and to tune the MNP's size and magnetic response. Here we present the first example of a tuneable, switchable magnetic delivery vehicle for nanomedical application. These are comprised of robust, tailored polymer vesicles (polymersomes) embedded with superparamagnetic magnetite MNPs (magnetopolymersomes) which show good MRI contrast (R2* = 148.8 s-1) and have a vacant core for loading of therapeutics. Critically, the magnetopolymersomes are produced by a pioneering nanoreactor method whereby electroporation triggers the in situ formation of MNPs within the vesicle membrane, offering a switchable, tuneable magnetic responsive theranostic delivery vehicle.

Gd2O3 nanoparticles stabilized by hydrothermally modified dextrose for positive contrast magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Babić-Stojić, Branka; Jokanović, Vukoman; Milivojević, Dušan; Požek, Miroslav; Jagličić, Zvonko; Makovec, Darko; Arsikin, Katarina; Paunović, Verica

2016-04-01

Gd2O3 nanoparticles of a few nm in size and their agglomerates dispersed in dextrose derived polymer template were synthesized by hydrothermal treatment. The produced nanosized material was investigated by TEM, FTIR spectroscopy, SQUID measurements and NMR relaxometry. Biological evaluation of this material was done by crystal violet and MTT assays to determine the cell viability. Longitudinal and transverse NMR relaxivities of water diluted Gd2O3 nanoparticle dispersions measured at the magnetic field of 1.5 T, estimated to be r1(Gd2O3)=9.6 s-1 mM-1 in the Gd concentration range 0.1-30 mM and r2(Gd2O3)=17.7 s-1 mM-1 in the lower concentration range 0.1-0.8 mM, are significantly higher than the corresponding relaxivities measured for the standard contrast agent r1(Gd-DTPA)=4.1 s-1 mM-1 and r2(Gd-DTPA)=5.1 s-1 mM-1. The ratio of the two relaxivities for Gd2O3 nanoparticles r2/r1=1.8 is suitable for T1-weighted imaging. Good MRI signal intensities of the water diluted Gd2O3 nanoparticle dispersions were recorded at lower Gd concentrations 0.2-0.8 mM. The Gd2O3 samples did not exert any significant cytotoxic effects at Gd concentrations of 0.2 mM and below. These properties of the produced Gd2O3 nanoparticles in hydrothermally modified dextrose make them promising for potential application in MRI for the design of a positive MRI contrast agent.

Superparamagnetic iron oxide nanoparticles for MRI: contrast media pharmaceutical company R&D perspective.

PubMed

Corot, Claire; Warlin, David

2013-01-01

Superparamagnetic iron oxide (SPIO) nanoparticles are a relatively large class of contrast agents for magnetic resonance imaging. According to their biodistribution, distinct classes of SPIO nanoparticles have been investigated for clinical applications either as macrophage imaging agents or blood pool agents. Contrast agents which are pharmaceutics followed the same development rules as therapeutic drugs. Several drawbacks such as clinical development difficulties, organization of market access and imaging technological developments have limited the widespread use of these products. SPIO nanoparticles that are composed of thousands iron atoms providing large T2* effects are particularly suitable for theranostic. Stem cell migration and immune cell trafficking, as well as targeted SPIO nanoparticles for molecular imaging studies are mainly at the stage of proof of concept. A major economic challenge in the development of molecular imaging associated with a therapeutic treatment/procedure is to define innovative business models compatible with the needs of all players taking into account that theranostic solutions are promising to optimize resource allocation and ensure that expensive treatments are prescribed to responding patients. © 2013 Wiley Periodicals, Inc.

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

NASA Astrophysics Data System (ADS)

Min, Yuanzeng; Roche, Kyle C.; Tian, Shaomin; Eblan, Michael J.; McKinnon, Karen P.; Caster, Joseph M.; Chai, Shengjie; Herring, Laura E.; Zhang, Longzhen; Zhang, Tian; Desimone, Joseph M.; Tepper, Joel E.; Vincent, Benjamin G.; Serody, Jonathan S.; Wang, Andrew Z.

2017-09-01

Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.

Applications of Magnetic Micro- and Nanoparticles in Biology and Medicine

NASA Astrophysics Data System (ADS)

Dobson, J.

2005-12-01

Magnetic nanoparticles were first proposed for biomedical applications in the 1970s - primarily as targeted drug delivery vehicles and MRI contrast agents. Since that time, such particles have found application in a variety of biomedical techniques. In addition to drug delivery, magnetic nanoparticles are now used routinely as MRI contrast agents as well as for magneto-immunoassay and cell sorting. More recently, magnetic micro- and nanoparticles have been used to investigate and manipulate cellular processes both in vitro and in vivo. In addition, biogenic magnetic nanoparticles are also produced in the human body. The iron storage protein, ferritin, consists of a superparamagnetic ferrihydrite core and biogenic magnetite (a ferrimagnet) has also been found in the brain and other organs. Though the role of ferritin and several other magnetic iron oxides in the body is well understood, the origin and role of biogenic magnetite is only now coming to light - and this may have profound implications for our understanding of neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases. This talk will review applications related to magnetic particle-mediated activation of cellular processes for tissue engineering applications and novel methods of magnetofection which have the potential to provide enhanced transfection for non-viral therapeutic gene delivery. It will also briefly highlight new techniques recently developed for the mapping and characterization of magnetic iron compounds related to neurodegenerative diseases and how rock magnetic techniques have been adapted to study magnetic iron compounds in the brain and other organs.

Improvements in Diagnostic Accuracy with Quantitative Dynamic Contrast-Enhanced MRI

DTIC Science & Technology

2011-12-01

Magnetic   Resonance   Imaging  during  the  Menstrual  Cylce:  Perfusion   Imaging  Signal   Enhanceent,  and  Influence  of...acquisition of quantitative images displaying the concentration of contrast media as well as MRI -detectable proton density. To date 21 patients have...truly  quantitative   images  of  a  dynamic  contrast-­‐enhanced  (DCE)   MRI  of  the

Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent.

PubMed

Santra, Santimukul; Jativa, Samuel D; Kaittanis, Charalambos; Normand, Guillaume; Grimm, Jan; Perez, J Manuel

2012-08-28

Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.

Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid arthritis using shuffle transform.

PubMed

Xanthopoulos, Emily; Hutchinson, Charles E; Adams, Judith E; Bruce, Ian N; Nash, Anthony F P; Holmes, Andrew P; Taylor, Christopher J; Waterton, John C

2007-01-01

Contrast-enhanced MRI is of value in assessing rheumatoid pannus in the hand, but the images are not always easy to quantitate. To develop and evaluate an improved measurement of volume of enhancing pannus (VEP) in the hand in human rheumatoid arthritis (RA). MR images of the hand and wrist were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing pannus was measured on images created by subtracting precontrast T1-weighted images from contrast-enhanced T1-weighted images using a shuffle transformation technique. Maximum intensity projection (MIP) and 3D volume rendering of the images were used as a guide to identify the pannus and any contrast-enhanced veins. Visualisation of pannus was much improved following the shuffle transform. Between 0 weeks and 1 week, the mean value of the within-subject coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15. There was no evidence of significant increased variability within the 13-week interval for the complete sample of patients. Volume of enhancing pannus can be measured reproducibly in the rheumatoid hand using 3D contrast-enhanced MRI and shuffle transform.

Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles

PubMed Central

Savard, Christian; Guérin, Annie; Drouin, Karine; Bolduc, Marilène; Laliberté-Gagné, Marie-Eve; Dumas, Marie-Christine; Majeau, Nathalie; Leclerc, Denis

2011-01-01

Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic. PMID:21747909

New developments in breast cancer therapy: role of iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Thoidingjam, Shivani; Bhan Tiku, Ashu

2017-06-01

Breast cancer is one of the leading causes of deaths in females worldwide. The high metastatic rate and drug resistance makes it one of the difficult cancers to treat. Early diagnosis and treatment are keys to better survival of breast cancer patients. Conventional treatment approaches like chemotherapy, radiotherapy and surgery suffer from major drawbacks. Novel approaches to improve cancer therapy with minimal damage to normal tissues and better quality of life for cancer patients need to be developed. Among various approaches used for treatment and diagnosis of breast cancer, use of nanoparticles (NPs) is coming up as a new and promising treatment regime. It can help overcome various limitations of conventional therapies like non-targeted effects, resistance to treatment, late diagnosis, etc. Among various nanoparticles studied for their biomedical applications, especially for breast cancer therapy, iron oxide nanoparticles (IONPs) are perhaps the most exciting due to their biocompatibility, biodegradability, size and properties like superparamagnetism. Besides, IONPs are also the only metal oxide nanoparticles approved for clinical use in magnetic resonance imaging (MRI) which is an added advantage for early detection. Therefore in this mini review, we are discussing the developments made in the use of IONPs for breast cancer therapy over the short span of the last five years i.e. 2010-2015. Since late diagnosis and therapy resistance are important drawbacks in breast cancer therapy, the potential of IONPs to overcome these limitations are also evaluated.

Development of PEGylated KMnF3 nanoparticles as a T1-weighted contrast agent: chemical synthesis, in vivo brain MR imaging, and accounting for high relaxivity

NASA Astrophysics Data System (ADS)

Liu, Zhi-Jun; Song, Xiao-Xia; Tang, Qun

2013-05-01

Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM-1 s-1) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF3 nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility.Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM-1 s-1) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or

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.

MRI biosensor for lead detection based on the DNAzyme-induced catalytic reaction.

PubMed

Xu, Liguang; Yin, Honghong; Ma, Wei; Wang, Libing; Kuang, Hua; Xu, Chuanlai

2013-11-21

A MRI biosensor for sensitive and specific detection of lead ions (Pb(2+)) was developed based on DNAzyme-induced cleavage of magnetic nanoparticles (MNPs). A low limit of detection (LOD) of 0.05 ng mL(-1) was obtained. This biosensor has the potential to serve as a general platform for the detection of heavy metal ions.

Nicotine-encapsulated poly(lactic-co-glycolic) acid nanoparticles improve neuroprotective efficacy against MPTP-induced parkinsonism.

PubMed

Tiwari, Manindra Nath; Agarwal, Swati; Bhatnagar, Priyanka; Singhal, Naveen Kumar; Tiwari, Shashi Kant; Kumar, Pradeep; Chauhan, Lalit Kumar Singh; Patel, Devendra Kumar; Chaturvedi, Rajnish Kumar; Singh, Mahendra Pratap; Gupta, Kailash Chand

2013-12-01

For some instances of Parkinson disease (PD), current evidence in the literature is consistent with reactive oxygen species being involved in the etiology of the disease. The management of PD is still challenging owing to its ambiguous etiology and lack of permanent cure. Because nicotine offers neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, the neuroprotective efficacy of nicotine-encapsulated poly(lactic-co-glycolic) acid (PLGA) nanoparticles and the underlying mechanism of improved efficacy, if any, over bulk nicotine were assessed in this study. The selected indicators of oxidative stress, dopaminergic neurodegeneration and apoptosis, were measured in both in vitro and rodent models of parkinsonism in the presence or absence of "nanotized" or bulk nicotine. The levels of dopamine and its metabolites were measured in the striatum, nicotine and its metabolite in the nigrostriatal tissues while the immunoreactivities of tyrosine hydroxylase (TH), metallothionein-III (MT-III), inducible nitric oxide synthase (iNOS) and microglial activation were checked in the substantia nigra of controls and treated mice. GSTA4-4, heme oxygenase (HO)-1, tumor suppressor protein 53 (p53), caspase-3, lipid peroxidation (LPO), and nitrite levels were measured in the nigrostriatal tissues. Nicotine-encapsulated PLGA nanoparticles improved the endurance of TH-immunoreactive neurons and the number of fiber outgrowths and increased the mRNA expression of TH, neuronal cell adhesion molecule, and growth-associated protein-43 over bulk against 1-methyl-4-phenyl pyridinium ion-induced degeneration in the in vitro model. MPTP reduced TH immunoreactivity and levels of dopamine and its metabolites and increased microglial activation, expression of GSTA4-4, iNOS, MT-III, HO-1, p53, and caspase-3, and levels of nitrite and LPO. Whereas both bulk nicotine and nicotine-encapsulated PLGA nanoparticles modulated the changes toward controls, the modulation

Magnetic vesicles as MRI-trackable biogenic nanovectors

NASA Astrophysics Data System (ADS)

Andriola Silva, Amanda K.; Luciani, Nathalie; Gazeau, Florence; Wilhelm, Claire

2012-03-01

Magnetic labeling renders cells MRI-detectable which provides attractive solutions for tracking the fate of a transplanted cell population. Understanding the interplay of magnetic nanoparticles and cells is then an important point that should not be neglected. Here we show that in the condition of food starvation, macrophage cells emit vesicles containing nanoparticles. First, we inferred the intracellular iron oxide load from the magnetophoretic velocity of cells at a calibrated magnetic field gradient. After magnetic labeling and culture in stress conditions, the intracellular iron oxide load was once more determined and a detectable difference was observed before and after stress. Moreover, we identified in the stress conditioned medium membrane vesicle structures carrying magnetic particles. Besides pointing out the role of cell-derived vesicles in the sequestration of the intracellular magnetic label, experiments also demonstrated that vesicles were able to chaperone the magnetic cargo into naïve cells.

Perfluorocarbon Nanoparticles:. A Theranostic Platform Technology

NASA Astrophysics Data System (ADS)

Lanza, Gregory M.; Winter, Patrick M.; Caruthers, Shelton D.; Hughes, Michael S.; Hu, Grace; Pan, Dipanjan; Schmieder, Anne H.; Pham, Christine; Wickline, Samuel A.

2013-09-01

Nanomedicine clearly offers unique tools to address intractable medical problems in cancer and cardiovascular disease from entirely new perspectives. Among the theranostic options emerging in this new wave of biotechnology development, the perfluorocarbon nanoparticles have shown robust potential in vivo for diagnosing, characterizing, treating and following proliferating cancers, progressive atherosclerosis, rheumatoid arthritis and much more. These molecular imaging agents have been demonstrated for use with ultrasound, MRI, CT, and SPECT/CT. Moreover, the synergism of imaging for confirmation of therapeutic delivery, for dosimetry, and for noninvasively following early treatment responses is discussed. Image-guided drug delivery based on nanotechnology is emerging as a powerful clinical opportunity, and PFC nanoparticles are among the leading technologies reaching clinical testing today with this potential.

Improved Tribological Performance of Amorphous Carbon (a-C) Coating by ZrO2 Nanoparticles

PubMed Central

Tang, Jinzhu; Ding, Qi; Zhang, Songwei; Wu, Guizhi; Hu, Litian

2016-01-01

Nanomaterials, such as Graphene, h-BN nanoparticles and MoS2 nanotubes, have shown their ability in improving the tribological performance of amorphous carbon (a-C) coatings. In the current study, the effectiveness of ZrO2 nanoparticles (ZrO2-NPs) in lubricating the self-mated nonhydrogenated a-C contacts was investigated in boundary lubrication regime. The results showed that 13% less friction and 50% less wear compared to the base oil were achieved by employing ZrO2-NPs in the base oil in self-mated a-C contacts. Via analyzing the ZrO2-NPs and the worn a-C surface after tests, it was found that the improved lubrication by ZrO2-NPs was based on “polishing effects”, which is a new phenomenon observed between a-C and nanoparticles. Under the “polishing effect”, micro-plateaus with extremely smooth surface and uniform height were produced on the analyzed a-C surface. The resulting topography of the a-C coating is suitable for ZrO2-NPs to act as nano-bearings between rubbing surfaces. Especially, the ZrO2-NPs exhibited excellent mechanical and chemical stability, even under the severe service condition, suggesting that the combination of nonhydrogenated a-C coating with ZrO2-NPs is an effective, long lasting and environment-friendly lubrication solution. PMID:28773916

Development of magneto-plasmonic nanoparticles for multimodal image-guided therapy to the brain.

PubMed

Tomitaka, Asahi; Arami, Hamed; Raymond, Andrea; Yndart, Adriana; Kaushik, Ajeet; Jayant, Rahul Dev; Takemura, Yasushi; Cai, Yong; Toborek, Michal; Nair, Madhavan

2017-01-05

Magneto-plasmonic nanoparticles are one of the emerging multi-functional materials in the field of nanomedicine. Their potential for targeting and multi-modal imaging is highly attractive. In this study, magnetic core/gold shell (MNP@Au) magneto-plasmonic nanoparticles were synthesized by citrate reduction of Au ions on magnetic nanoparticle seeds. Hydrodynamic size and optical properties of magneto-plasmonic nanoparticles synthesized with the variation of Au ions and reducing agent concentrations were evaluated. The synthesized magneto-plasmonic nanoparticles exhibited superparamagnetic properties, and their magnetic properties contributed to the concentration-dependent contrast in magnetic resonance imaging (MRI). The imaging contrast from the gold shell part of the magneto-plasmonic nanoparticles was also confirmed by X-ray computed tomography (CT). The transmigration study of the magneto-plasmonic nanoparticles using an in vitro blood-brain barrier (BBB) model proved enhanced transmigration efficiency without disrupting the integrity of the BBB, and showed potential to be used for brain diseases and neurological disorders.

Real-time motion analytics during brain MRI improve data quality and reduce costs.

PubMed

Dosenbach, Nico U F; Koller, Jonathan M; Earl, Eric A; Miranda-Dominguez, Oscar; Klein, Rachel L; Van, Andrew N; Snyder, Abraham Z; Nagel, Bonnie J; Nigg, Joel T; Nguyen, Annie L; Wesevich, Victoria; Greene, Deanna J; Fair, Damien A

2017-11-01

Head motion systematically distorts clinical and research MRI data. Motion artifacts have biased findings from many structural and functional brain MRI studies. An effective way to remove motion artifacts is to exclude MRI data frames affected by head motion. However, such post-hoc frame censoring can lead to data loss rates of 50% or more in our pediatric patient cohorts. Hence, many scanner operators collect additional 'buffer data', an expensive practice that, by itself, does not guarantee sufficient high-quality MRI data for a given participant. Therefore, we developed an easy-to-setup, easy-to-use Framewise Integrated Real-time MRI Monitoring (FIRMM) software suite that provides scanner operators with head motion analytics in real-time, allowing them to scan each subject until the desired amount of low-movement data has been collected. Our analyses show that using FIRMM to identify the ideal scan time for each person can reduce total brain MRI scan times and associated costs by 50% or more. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Overt naming fMRI pre- and post-TMS: Two nonfluent aphasia patients, with and without improved naming post-TMS.

PubMed

Martin, Paula I; Naeser, Margaret A; Ho, Michael; Doron, Karl W; Kurland, Jacquie; Kaplan, Jerome; Wang, Yunyan; Nicholas, Marjorie; Baker, Errol H; Alonso, Miguel; Fregni, Felipe; Pascual-Leone, Alvaro

2009-10-01

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a 'good responder' with improved naming and phrase length; P2 was a 'poor responder' without improved naming. Pre-TMS (10 years poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named). At 3 mo. post-TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post-TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre-TMS and at 3 mo. post-TMS (p < .02; p < .05, respectively). At 16 mo. there was also greater activation in L than R SMA (p < .08). At 46 mo. post-TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre-TMS, to scores ranging from 14 to 18 pictures, post-TMS (2-43 mo. post-TMS). His longest phrase length (Cookie Theft picture) improved from three words pre-TMS, to 5-6 words post-TMS. Pre-TMS (1.5 years poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post-TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1-2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at one word, post-TMS. Lesion site may play a role

Improving language mapping in clinical fMRI through assessment of grammar.

PubMed

Połczyńska, Monika; Japardi, Kevin; Curtiss, Susan; Moody, Teena; Benjamin, Christopher; Cho, Andrew; Vigil, Celia; Kuhn, Taylor; Jones, Michael; Bookheimer, Susan

2017-01-01

Brain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain. We compared grammar tests (items testing word order in actives and passives, wh -subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates. The grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior

Improvement in Therapeutic Efficacy and Reduction in Cellular Toxicity: Introduction of a Novel Anti-PSMA-Conjugated Hybrid Antiandrogen Nanoparticle.

PubMed

Thangavel, Chellappagounder; Perepelyuk, Maryna; Boopathi, Ettickan; Liu, Yi; Polischak, Steven; Deshpande, Deepak A; Rafiq, Khadija; Dicker, Adam P; Knudsen, Karen E; Shoyele, Sunday A; Den, Robert B

2018-05-07

Second generation antiandrogens have improved overall survival for men with metastatic castrate resistant prostate cancer; however, the antiandrogens result in suppression of androgen receptor (AR) activity in all tissues resulting in dose limiting toxicity. We sought to overcome this limitation through encapsulation in a prostate specific membrane antigen (PSMA)-conjugated nanoparticle. We designed and characterized a novel nanoparticle containing an antiandrogen, enzalutamide. Selectivity and enhanced efficacy was achieved through coating the particle with PSMA. The PSMA-conjugated nanoparticle was internalized selectively in AR expressing prostate cancer cells. It did not elicit an inflammatory effect. The efficacy of enzalutamide was not compromised through insertion into the nanoparticle; in fact, lower systemic drug concentrations of enzalutamide resulted in comparable clinical activity. Normal muscle cells were not impacted by the PSMA-conjugated containing antiandrogen. This approach represents a novel strategy to increase the specificity and effectiveness of antiandrogen treatment for men with castrate resistant prostate cancer. The ability to deliver higher drug concentrations in prostate cancer cells may translate into improved clinical end points including overall survival.

Engineering the lipid layer of lipid-PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability.

PubMed

Hu, Yun; Hoerle, Reece; Ehrich, Marion; Zhang, Chenming

2015-12-01

Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid-PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long-term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement. This paper reports the engineering of the lipid layer that encloses a polymeric nanoparticle, which can be used as a carrier for drug and vaccine molecules for targeted delivery. We demonstrated that the concentration of cholesterol is critical for the stability and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for the delivery of immune effector molecules. However, we found that hybrid nanoparticles with high cholesterol concentration tend to fuse during storage resulting in larger particles with decreased cellular uptake. This problem is

Single slice US-MRI registration for neurosurgical MRI-guided US

NASA Astrophysics Data System (ADS)

Pardasani, Utsav; Baxter, John S. H.; Peters, Terry M.; Khan, Ali R.

2016-03-01

Image-based ultrasound to magnetic resonance image (US-MRI) registration can be an invaluable tool in image-guided neuronavigation systems. State-of-the-art commercial and research systems utilize image-based registration to assist in functions such as brain-shift correction, image fusion, and probe calibration. Since traditional US-MRI registration techniques use reconstructed US volumes or a series of tracked US slices, the functionality of this approach can be compromised by the limitations of optical or magnetic tracking systems in the neurosurgical operating room. These drawbacks include ergonomic issues, line-of-sight/magnetic interference, and maintenance of the sterile field. For those seeking a US vendor-agnostic system, these issues are compounded with the challenge of instrumenting the probe without permanent modification and calibrating the probe face to the tracking tool. To address these challenges, this paper explores the feasibility of a real-time US-MRI volume registration in a small virtual craniotomy site using a single slice. We employ the Linear Correlation of Linear Combination (LC2) similarity metric in its patch-based form on data from MNI's Brain Images for Tumour Evaluation (BITE) dataset as a PyCUDA enabled Python module in Slicer. By retaining the original orientation information, we are able to improve on the poses using this approach. To further assist the challenge of US-MRI registration, we also present the BOXLC2 metric which demonstrates a speed improvement to LC2, while retaining a similar accuracy in this context.

Nanoparticles of adaptive supramolecular networks self-assembled from nucleotides and lanthanide ions.

PubMed

Nishiyabu, Ryuhei; Hashimoto, Nozomi; Cho, Ten; Watanabe, Kazuto; Yasunaga, Takefumi; Endo, Ayataka; Kaneko, Kenji; Niidome, Takuro; Murata, Masaharu; Adachi, Chihaya; Katayama, Yoshiki; Hashizume, Makoto; Kimizuka, Nobuo

2009-02-18

Amorphous nanoparticles of supramolecular coordination polymer networks are spontaneously self-assembled from nucleotides and lanthanide ions in water. They show intrinsic functions such as energy transfer from nucleobase to lanthanide ions and excellent performance as contrast enhancing agents for magnetic resonance imaging (MRI). Furthermore, adaptive inclusion properties are observed in the self-assembly process: functional materials such as fluorescent dyes, metal nanoparticles, and proteins are facilely encapsulated. Dyes in these nanoparticles fluoresce in high quantum yields with a single exponential decay, indicating that guest molecules are monomerically wrapped in the network. Gold nanoparticles and ferritin were also wrapped by the supramolecular shells. In addition, these nucleotide/lanthanide nanoparticles also serve as scaffolds for immobilizing enzymes. The adaptive nature of present supramolecular nanoparticles provides a versatile platform that can be utilized in a variety of applications ranging from material to biomedical sciences. As examples, biocompatibility and liver-directing characteristics in in vivo tissue localization experiments are demonstrated.

MRI in multiple sclerosis: current status and future prospects

PubMed Central

Bakshi, Rohit; Thompson, Alan J; Rocca, Maria A; Pelletier, Daniel; Dousset, Vincent; Barkhof, Frederik; Inglese, Matilde; Guttmann, Charles R G; Horsfield, Mark A; Filippi, Massimo

2008-01-01

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images. Magnetic resonance spectroscopy should improve in sensitivity and specificity with higher field strengths and should enable the detection of a wider array of metabolites. Diffusion imaging is moving closer to the goal of defining structural connectivity and, thereby, determining the functional significance of lesions at specific locations. Cell-specific imaging now seems feasible with new magnetic resonance contrast agents. The imaging of myelin water fraction brings the hope of providing a specific measure of myelin content. Ultra-high-field MRI increases sensitivity, but also presents new technical challenges. Here, we review these recent developments in MRI for MS, and also look forward to refinements in spinal-cord imaging, optic-nerve imaging, perfusion MRI, and functional MRI. Advances in MRI should improve our ability to diagnose, monitor, and understand the pathophysiology of MS. PMID:18565455

Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

PubMed

García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

2015-03-30

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

Cobalt ferrite nanoparticles with improved aqueous colloidal stability and electrophoretic mobility

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

Munjal, Sandeep, E-mail: drsandeepmunjal@gmail.com; Khare, Neeraj, E-mail: nkhare@physics.iitd.ernet.in

We have synthesized CoFe{sub 2}O{sub 4} (CFO) nanoparticles of size ∼ 12.2 nm by hydrothermal synthesis method. To control the size of these CFO nanoparticles, oleic acid was used as a surfactant. The inverse spinel phase of the synthesized nanoparticles was confirmed by X-ray diffraction method. As synthesized oleic acid coated CFO (OA@CFO) nanoparticles has very less electrophoretic mobility in the water and are not water dispersible. These OA@CFO nanoparticles were successfully turned into water soluble phase with a better colloidal aqueous stability, through a chemical treatment using citric acid. The modified citric acid coated CFO (CA@CFO) nanoparticles were dispersible inmore » water and form a stable aqueous solution with high electrophoretic mobility.« less

Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa.

PubMed

Cai, Xue; Conley, Shannon M; Nash, Zack; Fliesler, Steven J; Cooper, Mark J; Naash, Muna I

2010-04-01

The purpose of the present study was to test the therapeutic efficiency and safety of compacted-DNA nanoparticle-mediated gene delivery into the subretinal space of a juvenile mouse model of retinitis pigmentosa. Nanoparticles containing the mouse opsin promoter and wild-type mouse Rds gene were injected subretinally into mice carrying a haploinsufficiency mutation in the retinal degeneration slow (rds(+ or -)) gene at postnatal day (P)5 and 22. Control mice were either injected with saline, injected with uncompacted naked plasmid DNA carrying the Rds gene, or remained untreated. Rds mRNA levels peaked at postinjection day 2 to 7 (PI-2 to PI-7) for P5 injections, stabilized at levels 2-fold higher than in uninjected controls for both P5 and P22 injections, and remained elevated at the latest time point examined (PI-120). Rod function (measured by electroretinography) showed modest but statistically significant improvement compared with controls after both P5 and P22 injections. Cone function in nanoparticle-injected eyes reached wild-type levels for both ages of injections, indicating full prevention of cone degeneration. Ultrastructural examination at PI-120 revealed significant improvement in outer segment structures in P5 nanoparticle-injected eyes, while P22 injection had a modest structural improvement. There was no evidence of macrophage activation or induction of IL-6 or TNF-alpha mRNA in P5 or P22 nanoparticle-dosed eyes at either PI-2 or PI-30. Thus, compacted-DNA nanoparticles can efficiently and safely drive gene expression in both mitotic and postmitotic photoreceptors and retard degeneration in this model. These findings, using a clinically relevant treatment paradigm, illustrate the potential for application of nanoparticle-based gene replacement therapy for treatment of human retinal degenerations.-Cai, X., Conley, S. M., Nash, Z., Fliesler, S. J., Cooper, M. J., Naash, M. I. Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA

Improvement of magnetorheological finishing surface quality by nanoparticle jet polishing

NASA Astrophysics Data System (ADS)

Peng, Wenqiang; Li, Shengyi; Guan, Chaoliang; Shen, Xinmin; Dai, Yifan; Wang, Zhuo

2013-04-01

Nanoparticle jet polishing (NJP) is presented as a posttreatment to remove magnetorheological finishing (MRF) marks. In the NJP process the material is removed by chemical impact reaction, and the material removal rate of convex part is larger than that of the concave part. Smoothing thus can progress automatically in the NJP process. In the experiment, a silica glass sample polished by MRF was polished by NJP. Experiment results showed the MRF marks were removed clearly. The uniform polishing process shows that the NJP process can remove the MRF marks without destroying the original surface figure. The surface root-mean-square roughness is improved from 0.72 to 0.41 nm. power spectral density analysis indicates the surface quality is improved, and the experimental result validates effective removal of MRF marks by NJP.

Exploiting the wavelet structure in compressed sensing MRI.

PubMed

Chen, Chen; Huang, Junzhou

2014-12-01

Sparsity has been widely utilized in magnetic resonance imaging (MRI) to reduce k-space sampling. According to structured sparsity theories, fewer measurements are required for tree sparse data than the data only with standard sparsity. Intuitively, more accurate image reconstruction can be achieved with the same number of measurements by exploiting the wavelet tree structure in MRI. A novel algorithm is proposed in this article to reconstruct MR images from undersampled k-space data. In contrast to conventional compressed sensing MRI (CS-MRI) that only relies on the sparsity of MR images in wavelet or gradient domain, we exploit the wavelet tree structure to improve CS-MRI. This tree-based CS-MRI problem is decomposed into three simpler subproblems then each of the subproblems can be efficiently solved by an iterative scheme. Simulations and in vivo experiments demonstrate the significant improvement of the proposed method compared to conventional CS-MRI algorithms, and the feasibleness on MR data compared to existing tree-based imaging algorithms. Copyright © 2014 Elsevier Inc. All rights reserved.

Design and construction of multifunctional hyperbranched polymers coated magnetite nanoparticles for both targeting magnetic resonance imaging and cancer therapy.

PubMed

Mashhadi Malekzadeh, Asemeh; Ramazani, Ali; Tabatabaei Rezaei, Seyed Jamal; Niknejad, Hassan

2017-03-15

Magnetic drug targeting is a drug delivery strategy that can be used to improve the therapeutic efficiency on tumor cells and reduce the side effects on normal cells and tissues. The aim in this study is designing a novel multifunctional drug delivery system based on superparamagnetic nanoparticles for cancer therapy. Magnetic nanoparticles were synthesized by coprecipitation of iron oxide followed by coating with poly citric acid (PCA) dendritic macromolecules via bulk polymerization strategy. It was further surface-functionalized with poly(ethylene glycol) (PEG) and then to achieve tumor cell targeting property, folic acid was further incorporated to the surface of prepared carriers via a facile coupling reaction between the hydroxyl end group of the PEG and the carboxyl group of folic acid. The so prepared nanocarriers (Fe 3 O 4 @PCA-PEG-FA) were characterized by X-ray diffraction, TEM, TGA, FT-IR, DLS and VSM techniques. The room temperature VSM measurements showed that magnetic particles were superparamagnetic. Transmission electron microscopy and dynamic light scattering were also performed which revealed that size of nanocarriers was lying in the range of 10-49nm. Quercetin loading and release profiles of prepared nanocarriers showed that up to 83% of loaded drug was released in 250h. Fluorescent microscopy showed that the cellular uptake by folate receptor-overexpressing HeLa cells of the quercetin-loaded Fe 3 O 4 @PCA-PEG-FA nanoparticles was higher than that of non-folate conjugated nanoparticles. Thus, folate conjugation significantly increased nanoparticle cytotoxicity. Also, T 2 -weighted MRI images of Fe 3 O 4 @PCA-PEG-FA nanoparticles showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water and they also served as MRI contrast agents with relaxivities of 3.4mM -1 s -1 (r 1 ) and 99.8mM -1 s -1 (r 2 ). The results indicate that this multifunctional nanocarrier is a significant breakthrough

Use of a Quality Improvement Initiative to Achieve Consistent Reporting of Level of Suspicion for Tumor on Multiparametric Prostate MRI.

PubMed

Rosenkrantz, Andrew B; Pujara, Akshat C; Taneja, Samir S

2016-05-01

The purpose of this article is to evaluate the utility of a quality improvement (QI) initiative in achieving long-term adherence to an evolving structured format for reporting the level of suspicion for tumor on prostate MRI examinations. The original QI initiative occurred over a 4-month period in 2010, before which prostate MRI was reported using free text. The initiative consisted of development of a section-wide macro, an initial group training session, ordering physician input regarding the structured report's value, subsequent weekly sessions for ongoing review, and timely individualized feedback in instances of nonuse. The initial structured report included pick lists for describing the level of suspicion for tumor as negative, low, medium, or high. Pick lists were modified in 2011 to incorporate a 5-point Likert scale and again in 2015 to incorporate Prostate Imaging Data and Reporting System (PI-RADS) version 2. These refinements were implemented after accelerated training periods. The frequency of reports providing an MRI-based suspicion level during these periods was assessed. Fifty-five percent of reports provided an MRI-based level of suspicion for tumor before the initiative. For various cohorts evaluated after the initiative (using structured reports based on the low, medium, or high scheme; a numeric Likert scale; or PI-RADS), this frequency improved to 95-100% (p < 0.001). Among reports without a suspicion level, potential confounding factors included marked artifact from hip prosthesis and overt diffuse tumor. The QI initiative achieved excellent adherence in reporting a suspicion level for tumor on prostate MRI examinations. The described components of the initiative were useful for maintaining long-term adherence that persisted after serial modifications to the report lexicon.

Brief bursts of infrasound may improve cognitive function--an fMRI study.

PubMed

Weichenberger, Markus; Kühler, Robert; Bauer, Martin; Hensel, Johannes; Brühl, Rüdiger; Ihlenfeld, Albrecht; Ittermann, Bernd; Gallinat, Jürgen; Koch, Christian; Sander, Tilmann; Kühn, Simone

2015-10-01

At present, infrasound (sound frequency < 20 Hz; IS) is being controversially discussed as a potential mediator of several adverse bodily as well as psychological effects. However, it remains unclear, if and in what way IS influences cognition. Here, we conducted an fMRI experiment, in which 13 healthy participants were exposed to IS, while cognitive performance was assessed in an n-back working memory paradigm. During the task, short sinusoidal tone bursts of 12 Hz were administered monaurally with sound pressure levels that had been determined individually in a categorical loudness scaling session prior to the fMRI experiment. We found that task execution was associated with a significant activation of the prefrontal and the parietal cortex, as well as the striatum and the cerebellum, indicating the recruitment of a cognitive control network. Reverse contrast analysis (n-back with tone vs. n-back without tone) revealed a significant activation of the bilateral primary auditory cortex (Brodmann areas 41, 42). Surprisingly, we also found a strong, yet non-significant trend for an improvement of task performance during IS exposure. There was no correlation between performance and brain activity measures in tone and no-tone condition with sum scores of depression-, anxiety-, and personality factor assessment scales (BDI, STAIX1/X2, BFI-S). Although exerting a pronounced effect on cortical brain activity, we obtained no evidence for an impairment of cognition due to brief bursts of IS. On the contrary, potential improvement of working memory function introduces an entirely new aspect to the debate on IS-related effects. Copyright © 2015 Elsevier B.V. All rights reserved.

PREOPERATIVE MRI IMPROVES PREDICTION OF EXTENSIVE OCCULT AXILLARY LYMPH NODE METASTASES IN BREAST CANCER PATIENTS WITH A POSITIVE SENTINEL LYMPH NODE BIOPSY

PubMed Central

Loiselle, Christopher; Eby, Peter R.; Kim, Janice N.; Calhoun, Kristine E.; Allison, Kimberly H.; Gadi, Vijayakrishna K.; Peacock, Sue; Storer, Barry; Mankoff, David A.; Partridge, Savannah C.; Lehman, Constance D.

2014-01-01

Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy. PMID:24331270

Bacterially synthesized ferrite nanoparticles for magnetic hyperthermia applications.

PubMed

Céspedes, Eva; Byrne, James M; Farrow, Neil; Moise, Sandhya; Coker, Victoria S; Bencsik, Martin; Lloyd, Jonathan R; Telling, Neil D

2014-11-07

Magnetic hyperthermia uses AC stimulation of magnetic nanoparticles to generate heat for cancer cell destruction. Whilst nanoparticles produced inside magnetotactic bacteria have shown amongst the highest reported heating to date, these particles are magnetically blocked so that strong heating occurs only for mobile particles, unless magnetic field parameters are far outside clinical limits. Here, nanoparticles extracellularly produced by the bacteria Geobacter sulfurreducens are investigated that contain Co or Zn dopants to tune the magnetic anisotropy, saturation magnetization and nanoparticle sizes, enabling heating within clinical field constraints. The heating mechanisms specific to either Co or Zn doping are determined from frequency dependent specific absorption rate (SAR) measurements and innovative AC susceptometry simulations that use a realistic model concerning clusters of polydisperse nanoparticles in suspension. Whilst both particle types undergo magnetization relaxation and show heating effects in water under low AC frequency and field, only Zn doped particles maintain relaxation combined with hysteresis losses even when immobilized. This magnetic heating process could prove important in the biological environment where nanoparticle mobility may not be possible. Obtained SARs are discussed regarding clinical conditions which, together with their enhanced MRI contrast, indicate that biogenic Zn doped particles are promising for combined diagnostics and cancer therapy.

Ultrasmall lanthanide-doped nanoparticles as multimodal platforms

NASA Astrophysics Data System (ADS)

Yust, Brian G.; Pedraza, Francisco J.; Sardar, Dhiraj K.

2014-03-01

Recently, there has been a great amount of interest in nanoparticles which are able to provide a platform with high contrast for multiple imaging modalities in order to advance the tools available to biomedical researchers and physicians. However, many nanoparticles do not have ideal properties to provide high contrast in different imaging modes. In order to address this, ultrasmall lanthanide doped oxide and fluoride nanoparticles with strong NIR to NIR upconversion fluorescence and a strong magnetic response for magnetic resonance imaging (MRI) have been developed. Specifically, these nanoparticles incorporate gadolinium, dysprosium, or a combination of both into the nano-crystalline host to achieve the magnetic properties. Thulium, erbium, and neodymium codopants provide the strong NIR absorption and emission lines that allow for deeper tissue imaging since near infrared light is not strongly absorbed or scattered by most tissues within this region. This also leads to better image quality and lower necessary excitation intensities. As a part of the one pot synthesis, these nanoparticles are coated with peg, pmao, or d-glucuronic acid to make them water soluble, biocompatible, and bioconjugable due to the available carboxyl or amine groups. Here, the synthesis, morphological characterization, magnetic response, NIR emission, and the quantum yield will be discussed. Cytotoxicity tested through cell viability at varying concentrations of nanoparticles in growth media will also be discussed.

Biparametric MRI of the prostate.

PubMed

Scialpi, Michele; D'Andrea, Alfredo; Martorana, Eugenio; Malaspina, Corrado Maria; Aisa, Maria Cristina; Napoletano, Maria; Orlandi, Emanuele; Rondoni, Valeria; Scialpi, Pietro; Pacchiarini, Diamante; Palladino, Diego; Dragone, Michele; Di Renzo, Giancarlo; Simeone, Annalisa; Bianchi, Giampaolo; Brunese, Luca

2017-12-01

Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize and to guide prostatic targeted biopsy in patients with suspicious prostate cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the time required to perform the study, the use of gadolinium-based contrast agents and the lack of a guidance for management of score 3 lesions equivocal for significant PCa. In our experience the optimal and similar clinical results of the bpMRI in comparison to mpMRI are essentially related to the DWI that we consider the dominant sequence for detection suspicious PCa both in transition and in peripheral zone. In clinical practice, the adoption of bpMRI standardized scoring system, indicating the likelihood to diagnose a clinically significant PCa and establishing the management of each suspicious category (from 1 to 4), could represent the rationale to simplify and to improve the current interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data System version 2 (PI-RADS v2). In this review article we report and describe the current knowledge about bpMRI in the detection of suspicious PCa and a simplified PI-RADS based on bpMRI for management of each suspicious PCa categories to facilitate the communication between radiologists and urologists.

Biparametric MRI of the prostate

PubMed Central

Scialpi, Michele; D’Andrea, Alfredo; Martorana, Eugenio; Malaspina, Corrado Maria; Aisa, Maria Cristina; Napoletano, Maria; Orlandi, Emanuele; Rondoni, Valeria; Scialpi, Pietro; Pacchiarini, Diamante; Palladino, Diego; Dragone, Michele; Di Renzo, Giancarlo; Simeone, Annalisa; Bianchi, Giampaolo; Brunese, Luca

2017-01-01

Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize and to guide prostatic targeted biopsy in patients with suspicious prostate cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the time required to perform the study, the use of gadolinium-based contrast agents and the lack of a guidance for management of score 3 lesions equivocal for significant PCa. In our experience the optimal and similar clinical results of the bpMRI in comparison to mpMRI are essentially related to the DWI that we consider the dominant sequence for detection suspicious PCa both in transition and in peripheral zone. In clinical practice, the adoption of bpMRI standardized scoring system, indicating the likelihood to diagnose a clinically significant PCa and establishing the management of each suspicious category (from 1 to 4), could represent the rationale to simplify and to improve the current interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data System version 2 (PI-RADS v2). In this review article we report and describe the current knowledge about bpMRI in the detection of suspicious PCa and a simplified PI-RADS based on bpMRI for management of each suspicious PCa categories to facilitate the communication between radiologists and urologists. PMID:29201499

Magnetic nanoparticles: In vivo cancer diagnosis and therapy.

PubMed

Lima-Tenório, Michele K; Pineda, Edgardo A Gómez; Ahmad, Nasir M; Fessi, Hatem; Elaissari, Abdelhamid

2015-09-30

Recently, significant research efforts have been devoted to the finding of efficient approaches in order to reduce the side effects of traditional cancer therapy and diagnosis. In this context, magnetic nanoparticles have attracted much attention because of their unique physical properties, magnetic susceptibility, biocompatibility, stability and many more relevant characteristics. Particularly, magnetic nanoparticles for in vivo biomedical applications need to fulfill special criteria with respect to size, size distribution, surface charge, biodegradability or bio-eliminability and optionally bear well selected ligands for specific targeting. In this context, many routes have been developed to synthesize these materials, and tune their functionalities through intriguing techniques including functionalization, coating and encapsulation strategies. In this review article, the use of magnetic nanoparticles for cancer therapy and diagnosis is evaluated addressing potential applications in MRI, drug delivery, hyperthermia, theranostics and several other domains. In view of potential biomedical applications of magnetic nanoparticles, the review focuses on the most recent progress made with respect to synthetic routes to produce magnetic nanoparticles and their salient accomplishments for in vivo cancer diagnosis and therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Improving the Performance of Gold-Nanoparticle-Doped Solid-State Dye Laser Using Thermal Conversion Effect

NASA Astrophysics Data System (ADS)

An, N. T. M.; Lien, N. T. H.; Hoang, N. D.; Hoa, D. Q.

2018-04-01

Energy transfer between spherical gold nanoparticles with size of more than 15 nm and molecules of organic dye 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4 H-pyran (DCM) has been studied. Such radiative energy transfer led to high local temperature, giving rise to a bleaching effect that resulted in rapid degradation of the laser medium. Gold nanoparticles were dispersed at concentrations from 5 × 109 particles/mL to 5 × 1010 particles/mL in DCM polymethylmethacrylate polymer using a radical polymerization process with 2,2'-azobis(isobutyronitrile) (AIBN) as initiator. Using the fast thermoelectric cooling method, the laser medium stability was significantly improved. The output stability of a distributed feedback dye laser pumped by second-harmonic generation from a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser was investigated. Moreover, bidirectional energy transfer between gold nanoparticles and dye molecules was observed.

Membranes having aligned 1-D nanoparticles in a matrix layer for improved fluid separation

DOEpatents

Revanur, Ravindra; Lulevich, Valentin; Roh, Il Juhn; Klare, Jennifer E.; Kim, Sangil; Noy, Aleksandr; Bakajin, Olgica

2015-12-22

Membranes for fluid separation are disclosed. These membranes have a matrix layer sandwiched between an active layer and a porous support layer. The matrix layer includes 1-D nanoparticles that are vertically aligned in a porous polymer matrix, and which substantially extend through the matrix layer. The active layer provides species-specific transport, while the support layer provides mechanical support. A matrix layer of this type has favorable surface morphology for forming the active layer. Furthermore, the pores that form in the matrix layer tend to be smaller and more evenly distributed as a result of the presence of aligned 1-D nanoparticles. Improved performance of separation membranes of this type is attributed to these effects.

Highly Sensitive Detection of Caspase-3/7 Activity in Living Mice Using Enzyme-Responsive 19F MRI Nanoprobes.

PubMed

Akazawa, Kazuki; Sugihara, Fuminori; Nakamura, Tatsuya; Mizukami, Shin; Kikuchi, Kazuya

2018-05-16

Highly sensitive imaging of enzymatic activities in the deep tissues of living mammals provides useful information about their biological functions and for developing new drugs; however, such imaging is challenging. 19 F magnetic resonance imaging (MRI) is suitable for noninvasive visualization of enzymatic activities without endogenous background signals. Although various enzyme-responsive 19 F MRI probes have been developed, most cannot be used for in vivo imaging because of their low sensitivity. Recently, we developed unique nanoparticles, called FLAMEs, that are composed of a liquid perfluorocarbon core and a robust silica shell, and demonstrated their outstanding sensitivity in vivo. Here, we report a highly functionalized nanoprobe, FLAME-DEVD 2, with an OFF/ON 19 F MRI switch for detecting caspase-3/7 activity based on the paramagnetic relaxation enhancement effect. To improve the cleavage efficiency of peptides by caspase-3, we designed a novel Gd 3+ complex-conjugated peptide, DEVD X ( X = 1, 2), which is a substrate peptide sequence tandemly repeated X times, and demonstrated that DEVD 2 showed faster cleavage kinetics than DEVD 1. By incorporating this novel concept into a signal activation strategy, FLAME-DEVD 2 showed a high 19 F MRI signal enhancement rate in response to caspase-3 activity. After intravenous injection of FLAME-DEVD 2 and an apoptosis-inducing reagent, caspase-3/7 activity in the spleen of a living mouse was successfully imaged by 19 F MRI. This imaging platform shows great potential for highly sensitive detection of enzymatic activities in vivo.

Improved Electrochemical Performance of Carbon-Coated LiFeBO 3 Nanoparticles for Lithium-Ion Batteries

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

Li, Zhaoping; Wang, Yiping; Hu, Querui

2015-09-01

Carbon-coated LiFeBO 3 nanoparticles have been successfully prepared by surfactant-assisted ball milling and a size selection process based on centrifugal separation. We observed monodispersed LiFeBO 3 nanoparticles with dimensions of 10–20 nm by transmission electron microscope. The introduced surfactant acts as the dispersant as well as the carbon source for LiFeBO 3 nanoparticles. Greatly improved discharge capacities of 190.4 mA h g –1 at 0.1 C and 106.6 mA h g –1 at 1 C rate have been achieved in the LiFeBO 3 nanoparticles when cycling the cells between 1.0 V and 4.8 V. Meanwhile, the as-prepared micro-size LiFeBO 3more » electrodes show lower discharge capacities of 142 mA h g –1 and 93.3 mA h g –1 at 0.1 C and 1 C rates. Moreover, the post-treated LiFeBO 3 nanostructure has drastically enhanced the electrochemical performance due to the short diffusion length and ameliorated electrical contract between LiFeBO 3 nano particles.« less

Simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) for dynamic contrast-enhanced MRI of liver.

PubMed

Ning, Jia; Sun, Yongliang; Xie, Sheng; Zhang, Bida; Huang, Feng; Koken, Peter; Smink, Jouke; Yuan, Chun; Chen, Huijun

2018-05-01

To propose a simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) method for liver dynamic contrast-enhanced MRI. The proposed SAHA simultaneously acquired high temporal-resolution 2D images for vascular input function extraction using Cartesian sampling and 3D large-coverage high spatial-resolution liver dynamic contrast-enhanced images using golden angle stack-of-stars acquisition in an interleaved way. Simulations were conducted to investigate the accuracy of SAHA in pharmacokinetic analysis. A healthy volunteer and three patients with cirrhosis or hepatocellular carcinoma were included in the study to investigate the feasibility of SAHA in vivo. Simulation studies showed that SAHA can provide closer results to the true values and lower root mean square error of estimated pharmacokinetic parameters in all of the tested scenarios. The in vivo scans of subjects provided fair image quality of both 2D images for arterial input function and portal venous input function and 3D whole liver images. The in vivo fitting results showed that the perfusion parameters of healthy liver were significantly different from those of cirrhotic liver and HCC. The proposed SAHA can provide improved accuracy in pharmacokinetic modeling and is feasible in human liver dynamic contrast-enhanced MRI, suggesting that SAHA is a potential tool for liver dynamic contrast-enhanced MRI. Magn Reson Med 79:2629-2641, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Novel magnetic multicore nanoparticles designed for MPI and other biomedical applications: From synthesis to first in vivo studies

PubMed Central

Taupitz, Matthias; Ariza de Schellenberger, Angela; Kosch, Olaf; Eberbeck, Dietmar; Wagner, Susanne; Trahms, Lutz; Hamm, Bernd; Schnorr, Jörg

2018-01-01

Synthesis of novel magnetic multicore particles (MCP) in the nano range, involves alkaline precipitation of iron(II) chloride in the presence of atmospheric oxygen. This step yields green rust, which is oxidized to obtain magnetic nanoparticles, which probably consist of a magnetite/maghemite mixed-phase. Final growth and annealing at 90°C in the presence of a large excess of carboxymethyl dextran gives MCP very promising magnetic properties for magnetic particle imaging (MPI), an emerging medical imaging modality, and magnetic resonance imaging (MRI). The magnetic nanoparticles are biocompatible and thus potential candidates for future biomedical applications such as cardiovascular imaging, sentinel lymph node mapping in cancer patients, and stem cell tracking. The new MCP that we introduce here have three times higher magnetic particle spectroscopy performance at lower and middle harmonics and five times higher MPS signal strength at higher harmonics compared with Resovist®. In addition, the new MCP have also an improved in vivo MPI performance compared to Resovist®, and we here report the first in vivo MPI investigation of this new generation of magnetic nanoparticles. PMID:29300729

Studying neuroanatomy using MRI.

PubMed

Lerch, Jason P; van der Kouwe, André J W; Raznahan, Armin; Paus, Tomáš; Johansen-Berg, Heidi; Miller, Karla L; Smith, Stephen M; Fischl, Bruce; Sotiropoulos, Stamatios N

2017-02-23

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging and disease. Developments in MRI acquisition, image processing and data modeling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and for inferring microstructural properties; we also describe key artifacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, although methods need to improve and caution is required in interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works.

Multifunctional pH-sensitive polymeric nanoparticles for theranostics evaluated experimentally in cancer

NASA Astrophysics Data System (ADS)

Liu, Yongjun; Feng, Lixia; Liu, Tingxian; Zhang, Li; Yao, Yao; Yu, Dexin; Wang, Linlin; Zhang, Na

2014-02-01

A multifunctional pH-sensitive polymeric nanoparticle system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. The nanoparticles were self-assembled using the multi-block polymer poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and the pH-sensitive material poly(l-histidine)-poly(ethylene glycol)-biotin (PLH-PEG-biotin). The anti-hepatocellular carcinoma (HCC) drug sorafenib was encapsulated inside the nanoparticles. Gd ions were chelated to the DTPA groups which were distributed on the nanoparticle surface. Biotinylated vascular endothelial growth factor receptor (VEGFR) antibodies were linked to the surface biotin groups of nanoparticles through the avidin linker to form the target pH-sensitive theranostic nanoparticles (TPTN). TPTN exhibited spherical or ellipsoidal shapes, uniform particle size distribution (181.4 +/- 3.4 nm), positive zeta potential (14.95 +/- 0.60 mV), high encapsulation efficiency (95.02 +/- 1.47%) and drug loading (2.38 +/- 0.04%). The pH-sensitive sorafenib release from TPTN was observed under different pH values (47.81% at pH = 7.4 and 99.32% at pH = 5.0, respectively). In cell cytotoxicity studies, TPTN showed similar antitumor effect against HepG2 cells compared to solubilized sorafenib solution after pre-incubation in acid PBS (pH = 5.0) for 1 h in vitro (P > 0.05). In in vivo anti-tumor studies, TPTN showed significantly higher antitumor effect in H22 tumor (VEGFR overexpressed cell line) bearing mice compared to the solubilized sorafenib solution (oral or i.v. administration) group (P < 0.05). In the MRI test, the T1 relaxivity value of TPTN was 17.300 mM-1 s-1 which was 3.6 times higher than Magnevist® (r1 = 4.8 mM-1 s-1). As a positive contrast agent, TPTN exhibited higher resolution and longer imaging time (more than 90 min) in the MRI diagnosis of tumor-bearing mice compared to Magnevist® (more than 60 min). Furthermore, histological

Overt Naming fMRI Pre- and Post-TMS: Two Nonfluent Aphasia Patients, with and without Improved Naming Post-TMS

ERIC Educational Resources Information Center

Martin, Paula I.; Naeser, Margaret A.; Ho, Michael; Doron, Karl W.; Kurland, Jacquie; Kaplan, Jerome; Wang, Yunyan; Nicholas, Marjorie; Baker, Errol H.; Fregni, Felipe; Pascual-Leone, Alvaro

2009-01-01

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a "good responder" with improved naming…

Improved estimates of partial volume coefficients from noisy brain MRI using spatial context.

PubMed

Manjón, José V; Tohka, Jussi; Robles, Montserrat

2010-11-01

This paper addresses the problem of accurate voxel-level estimation of tissue proportions in the human brain magnetic resonance imaging (MRI). Due to the finite resolution of acquisition systems, MRI voxels can contain contributions from more than a single tissue type. The voxel-level estimation of this fractional content is known as partial volume coefficient estimation. In the present work, two new methods to calculate the partial volume coefficients under noisy conditions are introduced and compared with current similar methods. Concretely, a novel Markov Random Field model allowing sharp transitions between partial volume coefficients of neighbouring voxels and an advanced non-local means filtering technique are proposed to reduce the errors due to random noise in the partial volume coefficient estimation. In addition, a comparison was made to find out how the different methodologies affect the measurement of the brain tissue type volumes. Based on the obtained results, the main conclusions are that (1) both Markov Random Field modelling and non-local means filtering improved the partial volume coefficient estimation results, and (2) non-local means filtering was the better of the two strategies for partial volume coefficient estimation. Copyright 2010 Elsevier Inc. All rights reserved.

Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe magnetic manipulation of ependymal cells in live rodents

NASA Astrophysics Data System (ADS)

Peng, Yung-Kang; Lui, Cathy N. P.; Chen, Yu-Wei; Chou, Shang-Wei; Chou, Pi-Tai; Yung, Ken K. L.; Edman Tsang, S. C.

2018-01-01

Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents. As a result, using this engineered nanoparticle and associated technologies, identification, stimulation and transportation of labelled potentially multipotent NSCs from a specific location of a live brain to another by magnetic means for self-healing therapy can therefore be made possible.

Multiparametric Breast MRI of Breast Cancer

PubMed Central

Rahbar, Habib; Partridge, Savannah C.

2015-01-01

Synopsis Breast MRI has increased in popularity over the past two decades due to evidence for its high sensitivity for cancer detection. Current clinical MRI approaches rely on the use of a dynamic contrast enhanced (DCE-MRI) acquisition that facilitates morphologic and semi-quantitative kinetic assessments of breast lesions. The use of more functional and quantitative parameters, such as pharmacokinetic features from high temporal resolution DCE-MRI, apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) on diffusion weighted MRI, and choline concentrations on MR spectroscopy, hold promise to broaden the utility of MRI and improve its specificity. However, due to wide variations in approach among centers for measuring these parameters and the considerable technical challenges, robust multicenter data supporting their routine use is not yet available, limiting current applications of many of these tools to research purposes. PMID:26613883

Improved operative efficiency using a real-time MRI-guided stereotactic platform for laser amygdalohippocampotomy.

PubMed

Ho, Allen L; Sussman, Eric S; Pendharkar, Arjun V; Le, Scheherazade; Mantovani, Alessandra; Keebaugh, Alaine C; Drover, David R; Grant, Gerald A; Wintermark, Max; Halpern, Casey H

2018-04-01

OBJECTIVE MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive method for thermal destruction of benign or malignant tissue that has been used for selective amygdalohippocampal ablation for the treatment of temporal lobe epilepsy. The authors report their initial experience adopting a real-time MRI-guided stereotactic platform that allows for completion of the entire procedure in the MRI suite. METHODS Between October 2014 and May 2016, 17 patients with mesial temporal sclerosis were selected by a multidisciplinary epilepsy board to undergo a selective amygdalohippocampal ablation for temporal lobe epilepsy using MRgLITT. The first 9 patients underwent standard laser ablation in 2 phases (operating room [OR] and MRI suite), whereas the next 8 patients underwent laser ablation entirely in the MRI suite with the ClearPoint platform. A checklist specific to the real-time MRI-guided laser amydalohippocampal ablation was developed and used for each case. For both cohorts, clinical and operative information, including average case times and accuracy data, was collected and analyzed. RESULTS There was a learning curve associated with using this real-time MRI-guided system. However, operative times decreased in a linear fashion, as did total anesthesia time. In fact, the total mean patient procedure time was less in the MRI cohort (362.8 ± 86.6 minutes) than in the OR cohort (456.9 ± 80.7 minutes). The mean anesthesia time was significantly shorter in the MRI cohort (327.2 ± 79.9 minutes) than in the OR cohort (435.8 ± 78.4 minutes, p = 0.02). CONCLUSIONS The real-time MRI platform for MRgLITT can be adopted in an expedient manner. Completion of MRgLITT entirely in the MRI suite may lead to significant advantages in procedural times.

Silica nanoparticles for micro-particle imaging velocimetry: fluorosurfactant improves nanoparticle stability and brightness of immobilized iridium(III) complexes.

PubMed

Lewis, David J; Dore, Valentina; Rogers, Nicola J; Mole, Thomas K; Nash, Gerard B; Angeli, Panagiota; Pikramenou, Zoe

2013-11-26

To establish highly luminescent nanoparticles for monitoring fluid flows, we examined the preparation of silica nanoparticles based on immobilization of a cyclometalated iridium(III) complex and an examination of the photophysical studies provided a good insight into the Ir(III) microenvironment in order to reveal the most suitable silica nanoparticles for micro particle imaging velocimetry (μ-PIV) studies. Iridium complexes covalently incorporated at the surface of preformed silica nanoparticles, [Ir-4]@Si500-Z, using a fluorinated polymer during their preparation, demonstrated better stability than those without the polymer, [Ir-4]@Si500, as well as an increase in steady state photoluminescence intensity (and therefore particle brightness) and lifetimes which are increased by 7-fold compared with nanoparticles with the same metal complex attached covalently throughout their core, [Ir-4]⊂Si500. Screening of the nanoparticles in fluid flows using epi-luminescence microscopy also confirm that the brightest, and therefore most suitable particles for microparticle imaging velocimetry (μ-PIV) measurements are those with the Ir(III) complex immobilized at the surface with fluorosurfactant, that is [Ir-4]@Si500-Z. μ-PIV studies demonstrate the suitability of these nanoparticles as nanotracers in microchannels.

Design of a temperature measurement and feedback control system based on an improved magnetic nanoparticle thermometer

NASA Astrophysics Data System (ADS)

Du, Zhongzhou; Sun, Yi; Liu, Jie; Su, Rijian; Yang, Ming; Li, Nana; Gan, Yong; Ye, Na

2018-04-01

Magnetic fluid hyperthermia, as a novel cancer treatment, requires precise temperature control at 315 K-319 K (42 °C-46 °C). However, the traditional temperature measurement method cannot obtain the real-time temperature in vivo, resulting in a lack of temperature feedback during the heating process. In this study, the feasibility of temperature measurement and feedback control using magnetic nanoparticles is proposed and demonstrated. This technique could be applied in hyperthermia. Specifically, the triangular-wave temperature measurement method is improved by reconstructing the original magnetization response of magnetic nanoparticles based on a digital phase-sensitive detection algorithm. The standard deviation of the temperature in the magnetic nanoparticle thermometer is about 0.1256 K. In experiments, the temperature fluctuation of the temperature measurement and feedback control system using magnetic nanoparticles is less than 0.5 K at the expected temperature of 315 K. This shows the feasibility of the temperature measurement method for temperature control. The method provides a new solution for temperature measurement and feedback control in hyperthermia.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy

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

Lee, Dongkyu; Maeng, Inhee; Son, Joo-Hiuk

2009-04-19

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRImore » technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.« less

Gadolinium-modulated 19F signals from Perfluorocarbon Nanoparticles as a New Strategy for Molecular Imaging

PubMed Central

Neubauer, Anne M.; Myerson, Jacob; Caruthers, Shelton D.; Hockett, Franklin D.; Winter, Patrick M.; Chen, Junjie; Gaffney, Patrick J.; Robertson, J. David; Lanza, Gregory M.; Wickline, Samuel A.

2008-01-01

Recent advances in the design of fluorinated nanoparticles for magnetic resonance molecular imaging have enabled specific detection of 19F nuclei, providing unique and quantifiable spectral signatures. However, a pressing need for signal enhancement exists because the total 19F in imaging voxels is often limited. By directly incorporating a relaxation agent (gadolinium) into the lipid monolayer that surrounds the perfluorocarbon, a marked augmentation of the 19F signal from 200nm nanoparticles was achieved. This design increases the magnetic relaxation rate of the 19F nuclei 4-fold at 1.5 T and effects a 125% increase in signal, an effect which is maintained when they are targeted to human plasma clots. By varying the surface concentration of gadolinium, the relaxation effect can be quantitatively modulated to tailor particle properties. This novel strategy dramatically improves the sensitivity and range of 19F MRI/MRS and forms the basis for designing contrast agents capable of sensing their surface chemistry. PMID:18956457

Imaging transplanted stem cells in real time using an MRI dual-contrast method

PubMed Central

Ngen, Ethel J.; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-01-01

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies. PMID:26330231

Imaging transplanted stem cells in real time using an MRI dual-contrast method.

PubMed

Ngen, Ethel J; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-09-02

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

Ag-doped manganite nanoparticles: new materials for temperature-controlled medical hyperthermia.

PubMed

Melnikov, O V; Gorbenko, O Yu; Markelova, M N; Kaul, A R; Atsarkin, V A; Demidov, V V; Soto, C; Roy, E J; Odintsov, B M

2009-12-15

The purpose of this study was to introduce newly synthesized nanomaterials as an alternative to superparamagnetic ironoxide based particles (SPIO) and thus to launch a new platform for highly controllable hyperthermia cancer therapy and imaging. The new material that forms the basis for this article is lanthanum manganite particles with silver ions inserted into the perovskite lattice: La(1-x)Ag(x)MnO(3+delta). Adjusting the silver doping level, it is possible to control the Curie temperature (T(c)) in the hyperthermia range of interest (41-44 degrees C). A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) is suggested. New nanoparticles are stable, and their properties were not affected by the typical ambient conditions in the living tissue. It is possible to monitor the particle uptake and retention by MRI. When these particles are placed into an alternating magnetic field, their temperature increases to the definite value near T(c) and then remains constant if the magnetic field is maintained. During the hyperthermia procedure, the temperature can be restricted, thereby preventing the necrosis of normal tissue. A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) was suggested. Ag-doped perovskite manganites particles clearly demonstrated the effect of adjustable Curie temperature necessary for highly controllable cellular hyperthermia. The magnetic relaxation properties of the particles are comparable with that of SPIO, and so we were able to monitor the particle movement and retention by MRI. Thus, the new material combines the MRI contrast enhancement capability with targeted hyperthermia treatment.

Improved Chemical Stability and Antiproliferative Activities of Curcumin-Loaded Nanoparticles with a Chitosan Chlorogenic Acid Conjugate.

PubMed

Fan, Yuting; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

2017-12-13

A chitosan (CS)-chlorogenic acid (CA) conjugate was successfully prepared through free-radical-induced protocols with a substitution of CA on CS of 103.5 mg/g. ATR-FTIR and 1 H NMR results validated the covalent conjugation of CA onto CS. XRD results indicated the decrease of crystallinity after CA conjugation. DPPH-scavenging activity and reducing-power studies indicated that the CS-CA conjugate had stronger antioxidant activity than chitosan. The particle diameters of curcumin-loaded CS and CS-CA nanoparticles simultaneously formed by ionic gelling in the presence of tripolyphosphate (TPP) were less than 300 nm (243.6 and 256.5 nm, respectively), and zeta-potential values between 25 and 30 mV were obtained. TEM results showed that the nanoparticles were spherically shaped and homogeneously dispersed. Curcumin with the CS-CA conjugate showed better heat stability than with CA at both temperatures (25 and 95 °C) (p <0.05). Curcumin release was inhibited by the CS-CA conjugate. The total release amount of curcumin from CS and CS-CA-conjugate nanoparticles were 70.5 and 61.7%, respectively (p <0.05). A methyl thiazolyl tetrazolium (MTT) assay showed that the antiproliferative activity of curcumin in CS-CA nanoparticles was remarkably higher than that in CS nanoparticles because of the higher chemical stability. The results suggest that CS-CA-based nanoparticles are promising candidates for the encapsulation and controlled release of hydrophobic, bioactive compounds and can improve these compounds' chemical stabilities and anticancer activities.

Functional mesoporous silica nanoparticles for bio-imaging applications.

PubMed

Cha, Bong Geun; Kim, Jaeyun

2018-03-22

Biomedical investigations using mesoporous silica nanoparticles (MSNs) have received significant attention because of their unique properties including controllable mesoporous structure, high specific surface area, large pore volume, and tunable particle size. These unique features make MSNs suitable for simultaneous diagnosis and therapy with unique advantages to encapsulate and load a variety of therapeutic agents, deliver these agents to the desired location, and release the drugs in a controlled manner. Among various clinical areas, nanomaterials-based bio-imaging techniques have advanced rapidly with the development of diverse functional nanoparticles. Due to the unique features of MSNs, an imaging agent supported by MSNs can be a promising system for developing targeted bio-imaging contrast agents with high structural stability and enhanced functionality that enable imaging of various modalities. Here, we review the recent achievements on the development of functional MSNs for bio-imaging applications, including optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and multimodal imaging for early diagnosis. With further improvement in noninvasive bio-imaging techniques, the MSN-supported imaging agent systems are expected to contribute to clinical applications in the future. This article is categorized under: Diagnostic Tools > In vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2018 Wiley Periodicals, Inc.

Breast MRI: EUSOBI recommendations for women's information.

PubMed

Mann, Ritse M; Balleyguier, Corinne; Baltzer, Pascal A; Bick, Ulrich; Colin, Catherine; Cornford, Eleanor; Evans, Andrew; Fallenberg, Eva; Forrai, Gabor; Fuchsjäger, Michael H; Gilbert, Fiona J; Helbich, Thomas H; Heywang-Köbrunner, Sylvia H; Camps-Herrero, Julia; Kuhl, Christiane K; Martincich, Laura; Pediconi, Federica; Panizza, Pietro; Pina, Luis J; Pijnappel, Ruud M; Pinker-Domenig, Katja; Skaane, Per; Sardanelli, Francesco

2015-12-01

This paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna-The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI. • Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7-14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation.

Development of an MRI-compatible digital SiPM detector stack for simultaneous PET/MRI.

PubMed

Düppenbecker, Peter M; Weissler, Bjoern; Gebhardt, Pierre; Schug, David; Wehner, Jakob; Marsden, Paul K; Schulz, Volkmar

2016-02-01

Advances in solid-state photon detectors paved the way to combine positron emission tomography (PET) and magnetic resonance imaging (MRI) into highly integrated, truly simultaneous, hybrid imaging systems. Based on the most recent digital SiPM technology, we developed an MRI-compatible PET detector stack, intended as a building block for next generation simultaneous PET/MRI systems. Our detector stack comprises an array of 8 × 8 digital SiPM channels with 4 mm pitch using Philips Digital Photon Counting DPC 3200-22 devices, an FPGA for data acquisition, a supply voltage control system and a cooling infrastructure. This is the first detector design that allows the operation of digital SiPMs simultaneously inside an MRI system. We tested and optimized the MRI-compatibility of our detector stack on a laboratory test bench as well as in combination with a Philips Achieva 3 T MRI system. Our design clearly reduces distortions of the static magnetic field compared to a conventional design. The MRI static magnetic field causes weak and directional drift effects on voltage regulators, but has no direct impact on detector performance. MRI gradient switching initially degraded energy and timing resolution. Both distortions could be ascribed to voltage variations induced on the bias and the FPGA core voltage supply respectively. Based on these findings, we improved our detector design and our final design shows virtually no energy or timing degradations, even during heavy and continuous MRI gradient switching. In particular, we found no evidence that the performance of the DPC 3200-22 digital SiPM itself is degraded by the MRI system.

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

PubMed

Jambor, Ivan; Boström, Peter J; Taimen, Pekka; Syvänen, Kari; Kähkönen, Esa; Kallajoki, Markku; Perez, Ileana Montoya; Kauko, Tommi; Matomäki, Jaakko; Ettala, Otto; Merisaari, Harri; Kiviniemi, Aida; Dean, Peter B; Aronen, Hannu J

2017-10-01

To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T 2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. © 2017 International Society for Magnetic Resonance in Medicine.

Overt Naming fMRI Pre- and Post- TMS: Two Nonfluent Aphasia Patients, with and without Improved Naming Post- TMS

PubMed Central

Martin, Paula I; Naeser, Margaret A.; Ho, Michael; Doron, Karl W.; Kurland, Jacquie; Kaplan, Jerome; Wang, Yunyan; Nicholas, Marjorie; Baker, Errol H.; Alonso, Miguel; Fregni, Felipe; Pascual-Leone, Alvaro

2009-01-01

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post- a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received ten, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a ‘good responder’ with improved naming and phrase length; P2 was a ‘poor responder’ without improved naming. Pre- TMS (10 yr. poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named. At 3 mo. post- TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post- TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre- TMS and at 3 mo. post- TMS (p<.02; p<.05, respectively). At 16 mo. there was also greater activation in L than R SMA (p<.08). At 46 mo. post- TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre- TMS, to scores ranging from 14-18 pictures, post- TMS (2 mo. to 43 mo. post- TMS). His longest phrase length (Cookie Theft picture) improved from 3 words pre- TMS, to 5-6 words post- TMS. Pre- TMS (1.5 yr. poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post- TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1-2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at 1 word, post- TMS. Lesion site may

Development of a synoptic MRI report for primary rectal cancer.

PubMed

Spiegle, Gillian; Leon-Carlyle, Marisa; Schmocker, Selina; Fruitman, Mark; Milot, Laurent; Gagliardi, Anna R; Smith, Andy J; McLeod, Robin S; Kennedy, Erin D

2009-12-02

Although magnetic resonance imaging (MRI) is an important imaging modality for pre-operative staging and surgical planning of rectal cancer, to date there has been little investigation on the completeness and overall quality of MRI reports. This is important because optimal patient care depends on the quality of the MRI report and clear communication of these reports to treating physicians. Previous work has shown that the use of synoptic pathology reports improves the quality of pathology reports and communication between physicians. The aims of this project are to develop a synoptic MRI report for rectal cancer and determine the enablers and barriers toward the implementation of a synoptic MRI report for rectal cancer in the clinical setting. A three-step Delphi process with an expert panel will extract the key criteria for the MRI report to guide pre-operative chemoradiation and surgical planning following a review of the literature, and a synoptic template will be developed. Furthermore, standardized qualitative research methods will be used to conduct interviews with radiologists to determine the enablers and barriers to the implementation and sustainability of the synoptic MRI report in the clinic setting. Synoptic MRI reports for rectal cancer are currently not used in North America and may improve the overall quality of MRI report and communication between physicians. This may, in turn, lead to improved patient care and outcomes for rectal cancer patients.

Improved hepatic arterial fraction estimation using cardiac output correction of arterial input functions for liver DCE MRI

NASA Astrophysics Data System (ADS)

Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

2017-02-01

Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7  ±  1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n  =  9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p  =  0.066), total liver blood flow (TLBF) (p  =  0.101), hepatic arterial (HA) fraction (p  =  0.895), mean transit time (MTT) (p  =  0.646), distribution volume (DV) (p  =  0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland-Altman 95% limits-of-agreement (BA95%LoA)  ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min-1/100 g, BA95%LoA  ±506.1 ml min-1/100 g, CoV 64.1% versus 0.9 ml min-1/100 g, ±562.8 ml min-1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min-1/100 g, BA95%LoA  ±586.7 ml min-1/ 100 g, CoV 58.3% versus 13.3 ml min-1/100 g, ±661.5 ml min-1/100 g, 60.9% respectively with correction

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

2014-06-01

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

MRI-only treatment planning: benefits and challenges

NASA Astrophysics Data System (ADS)

Owrangi, Amir M.; Greer, Peter B.; Glide-Hurst, Carri K.

2018-03-01

Over the past decade, the application of magnetic resonance imaging (MRI) has increased, and there is growing evidence to suggest that improvements in the accuracy of target delineation in MRI-guided radiation therapy may improve clinical outcomes in a variety of cancer types. However, some considerations should be recognized including patient motion during image acquisition and geometric accuracy of images. Moreover, MR-compatible immobilization devices need to be used when acquiring images in the treatment position while minimizing patient motion during the scan time. Finally, synthetic CT images (i.e. electron density maps) and digitally reconstructed radiograph images should be generated from MRI images for dose calculation and image guidance prior to treatment. A short review of the concepts and techniques that have been developed for implementation of MRI-only workflows in radiation therapy is provided in this document.

Dysprosium-Modified Tobacco Mosaic Virus Nanoparticles for Ultra-High-Field Magnetic Resonance and Near-Infrared Fluorescence Imaging of Prostate Cancer.

PubMed

Hu, He; Zhang, Yifan; Shukla, Sourabh; Gu, Yuning; Yu, Xin; Steinmetz, Nicole F

2017-09-26

The increasing prevalence of ultra-high-field magnetic resonance imaging (UHFMRI) in biomedical research and clinical settings will improve the resolution and diagnostic accuracy of MRI scans. However, better contrast agents are needed to achieve a satisfactory signal-to-noise ratio. Here, we report the synthesis of a bimodal contrast agent prepared by loading the internal cavity of tobacco mosaic virus (TMV) nanoparticles with a dysprosium (Dy 3+ ) complex and the near-infrared fluorescence (NIRF) dye Cy7.5. The external surface of TMV was conjugated with an Asp-Gly-Glu-Ala (DGEA) peptide via a polyethylene glycol linker to target integrin α 2 β 1 . The resulting nanoparticle (Dy-Cy7.5-TMV-DGEA) was stable and achieved a high transverse relaxivity in ultra-high-strength magnetic fields (326 and 399 mM -1 s -1 at 7 and 9.4 T, respectively). The contrast agent was also biocompatible (low cytotoxicity) and targeted PC-3 prostate cancer cells and tumors in vitro and in vivo as confirmed by bimodal NIRF imaging and T 2 -mapping UHFMRI. Our results show that Dy-Cy7.5-TMV-DGEA is suitable for multiscale MRI scanning from the cellular level to the whole body, particularly in the context of UHFMRI applications.