Lectin–Gd-Loaded Chitosan Hydrogel Nanoparticles: A New Biospecific Contrast Agent for MRI (original) (raw)
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International Journal of Molecular Sciences, 2022
The aim of this study was to investigate the biocompatibility of contrast agents, such as gadolinium 1, 4, 7, 10 tetraazacyclo-dodecane tetraacetic acid (GdDOTA) and gadolinium dioctyl terephthalate (GdDOTP), encapsulated in a polymeric matrix containing chitosan and hyaluronic acid using RAW264.7 murine macrophages and human blood samples. The cell viability and cytotoxicity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, while cell cycle analysis was determined in RAW264.7 cells using flow cytometry. The mitochondrial membrane potential (MMP), hemolytic index, complement activation, and thrombogenic potential of gadolinium (Gd) containing nanohydrogels were measured by fluorometric and spectrophotometric methods. Taken together, our results demonstrate the good bio- and hemocompatibility of chitosan-based nanohydrogels with the RAW264.7 cell line and human blood cells, suggesting that these could be used ...
Nanomaterials (Basel, Switzerland), 2018
Although the research on nanogels incorporating Gd chelates for theranostic applications has grown exponentially in recent years, knowledge about their biocompatibility is limited. We compared the biocompatibility of Gd-loaded hyaluronic acid-chitosan-based nanogels (GdCA⊂CS-TPP/HA) with two chitosan concentrations (2.5 and 1.5 mg·mL respectively) using SVEC4-10 murine lymph node endothelial cells. The sulforhodamine B method and released lactate dehydrogenase (LDH) activity were used as cell viability tests. Reactive oxygen species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) were measured by spectrophotometric and fluorimetric methods. Nrf-2 protein expression was evaluated by Western blot analysis and genotoxicity by alkaline comet assay. After 24 h, the cells viability was not affected by all types and doses of nanogels. The increase of ROS induced a low decrease of GSH concentration and a time-dependent raise of MDA one was produced by citric GdDOTA⊂CS-TPP/HA with...
Nanomaterials
Chitosan is a fibrous compound derived from chitin, which is the second most abundant natural polysaccharide and is produced by crustaceans, including crabs, shrimps, and lobsters. Chitosan has all of the important medicinal properties, including biocompatibility, biodegradability, and hydrophilicity, and it is relatively nontoxic and cationic in nature. Chitosan nanoparticles are particularly useful due to their small size, providing a large surface-to-volume ratio, and physicochemical properties that may differ from that of their bulk counterparts; thus, chitosan nanoparticles (CNPs) are widely used in biomedical applications and, particularly, as contrast agents for medical imaging and as vehicles for drug and gene delivery into tumors. Because CNPs are formed from a natural biopolymer, they can readily be functionalized with drugs, RNA, DNA, and other molecules to target a desired result in vivo. Furthermore, chitosan is approved by the United States Food and Drug Administration...
Chitosan-based systems for molecular imaging
Advanced Drug Delivery Reviews, 2010
Imaging techniques Imaging agents MRI CT Ultrasound Optical imaging Molecular imaging enables the non-invasive assessment of biological and biochemical processes in living subjects. Such technologies therefore have the potential to enhance our understanding of disease and drug activity during preclinical and clinical drug development. Molecular imaging allows a repetitive and noninvasive study of the same living subject using identical or alternative biological imaging assays at different time points, thus harnessing the statistical power of longitudinal studies, and reducing the number of animals required and cost. Chitosan is a hydrophilic and non-antigenic biopolymer and has a low toxicity toward mammalian cells. Hence, it has great potential as a biomaterial because of its excellent biocompatibility. Conjugated to additional materials, chitosan composites result in a new class of biomaterials that possess mechanical, physicochemical and functional properties, which have potential for use in advanced biomedical imaging applications. The present review will discuss the strengths, limitations and challenges of molecular imaging as well as applications of chitosan nanoparticles in the field of molecular imaging.
Macromolecular bioscience, 2015
Gd-DTPA-loaded chitosan-poly(acrylic acid) nanoparticles (Gd-DTPA@CS-PAA NPs) were formulated based on the reaction system of water-soluble polymer-monomer pairs of acrylic acid in chitosan solution followed by sorption of Gd-DTPA. Morphological investigations revealed the spherical shape of these NPs with about 220 nm particle size. These NPs showed charge reversal characteristic in acidic solution. In vitro and in vivo magnetic characteristics of these NPs were explored to estimate their utilization in targeted enhanced magnetic resonance imaging. Relaxation studies showed that these NPs possessed pH susceptible relaxation properties, which could introduce in vivo-specific distribution of contrast agent. MRI experiment showed that these nanoparticles had better results in contrast enhancement, and the concentration of contrast agent increased in liver and brain with increment in time. Thus, these NPs could maintain in vivo long circulation and high relaxation rate and were suitabl...
Nanomedicine: Nanotechnology, Biology and Medicine, 2017
Bioreactivity of superparamagnetic iron oxide nanoparticles (SPION) coated with thin layers of either cationic or anionic chitosan derivatives and serving as contrast agents in magnetic resonance imaging (MRI) was studied in vivo using BALB/c mouse model. Synthesized dual-modal fluorescing SPION were tracked in time using both fluorescent imaging and MRI. Although SPION started to be excreted by kidneys relatively shortly after administration they were uptaken by liver enhancing MRI contrast even up to 7 days. Importantly, chitosan-coated SPION caused only mild activation of acute phase response not effecting biochemical parameters of blood. Liver histology indicated the presence of SPION and some increase in the number of Kupffer cells. The overall results indicated that SPION coated with ultrathin layers of chitosan ionic derivatives can serve as T 2 contrast agents for diagnosis of liver diseases or imaging of other organs assuming the dose is optimized according to the need.
Carbohydrate Polymers, 2010
We have prepared chitosan (CH)-gadolinium (Gd) diethylenetriaminepentaacetic acid (DTPA) conjugates that have potential as contrast agents for magnetic resonance imaging. Conjugates were synthesized starting with low molecular weight chitosan (25 kDa and 96% degree of deacetylation (noted DDA)) by covalent linkage of DTPA to chitosan amine groups confirmed by Fourier transform infrared spectroscopy (FTIR). Different DTPA/amine ratios were used to obtain different degrees of DTPA conjugation (10-20%), determined by nuclear magnetic resonance ( 1 H NMR) spectroscopy, a colorimetric assay, and isothermal titration calorimetry (ITC). After preparation of chitosan-DTPA complexes with Gd, polyelectrolyte complexes were assembled with plasmid DNA pEGFPLuc (6367 bp) and investigated using scanning electron microscopy and scanning transmission electron microscopy. Particles were spherical with diameters in the range of 30-150 nm. The presence of gadolinium in the nanoparticles was confirmed by energy dispersive X-ray spectroscopy. Gd was located preferentially in a 2-5 nm wide area surrounding the nanoparticles.
Molecular Imaging and Biology, 2011
Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer-DTPA compounds were characterised by 1 H NMR and mass spectrometry. The final lectin-DTPA-polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents.
Journal of Nanobiotechnology, 2008
This project involved the synthesis of N-hexanoyl chitosan or simply modified chitosan (MC) stabilized iron oxide nanoparticles (MC-IOPs) and the biological evaluation of MC-IOPs. IOPs containing MC were prepared using conventional methods, and the extent of cell uptake was evaluated using mouse macrophages cell line (RAW cells). MC-IOPs were found to rapidly associate with the RAW cells, and saturation was typically reached within the 24 h of incubation at 37°C. Nearly 8.53 ± 0.31 pg iron/cell were bound or internalized at saturation. From these results, we conclude that MC-IOPs effectively deliver into RAW cells in vitro and we also hope MC-IOPs can be used for MRI enhancing agents in biomedical fields.
Histochemistry and Cell Biology, 2010
We are developing a nanoparticulate histochemical reagent designed for histochemistry in living animals (molecular imaging), which should finally be useful in clinical imaging applications. The iterative development procedure employed involves conceptual design of the reagent, synthesis and testing of the reagent, then redesign based on data from the testing; each cycle of testing and development generates a new generation of nanoparticles, and this report describes the synthesis and testing of the third generation. The nanoparticles are based on human serum albumin and the imaging modality selected is magnetic resonance imaging (MRI). Testing the second particle generation with newly introduced techniques revealed the presence of impurities in the final product, therefore we replaced dialysis with diafiltration. We introduced further testing methods including thin layer chromatography, arsenazo III as chromogenic assay for gadolinium, and several versions of polyacrylamide gel electrophoresis, for physicochemical characterisation of the nanoparticles and intermediate synthesis compounds. The high grade of chemical purity achieved by combined application of these methodologies allowed standardised particle sizes to be achieved (low dispersities), and accurate measurement of critical physicochemical parameters influencing particle size and imaging properties. Regression plots confirmed the high purity and standardisation. The good degree of quantitative physicochemical characterisation aided our understanding of the nanoparticles and allowed a conceptual model of them to be prepared. Toxicological screening demonstrated the extremely low toxicity of the particles. The high magnetic resonance relaxivities and enhanced mechanical stability of the particles make them an excellent platform for the further development of MRI molecular imaging.