Biodistribution and clearance of quantum dots in small animals (original) (raw)
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Journal of Pharmaceutical Investigation, 2013
Nano-sized materials are increasingly used in cosmetics, diagnosis, imaging, and drug delivery. It also involved in specific functionality with lymphoid systems. However, the toxicity and mechanisms of quantum dots (QDs) uptake into mammalian cells are poorly understood. Our study was to investigate the toxicity and tissue uptake of polyethylene glycol-folic acid-conjugated (PEG-FA), and only polyethylene glycol-conjugated (PEG) cadmium selenide/cadmium sulfide (CdSe/CdS) QDs using precision-cut spleen slices of Sprague-Dawley (SD) rats. QDs were treated with different doses (0-300 nM) to the spleen of SD rats, and their toxic effects and tissue uptake were examined by LDH, NADPH oxidase, and histological analyses. No dose-dependent changes in LDH were observed. But high uptake of the QD-PEG-FA into spleen slices was observed by fluorescence microscopic examination in dose-dependent manner, while most of the QD-PEG was found on the edge of the slices. The NADPH oxidase activity was increased at high dose (300 nM) in both QD-PEG-FA-or QD-PEG-treated spleen slices indicating oxidative stresses. No damages were noticed in histological study confirming no toxicity in both types of QDs. Based on the above observations, we may conclude that surface coating property is an important factor in determining QDs uptake into mammalian cells. These findings provide insight into the specific mechanism of QDs uptake in cells.
The cytotoxic effects of polymer-coated quantum dots and restrictions for live cell applications
Biomaterials, 2012
The interest in the biomedical use of highly fluorescent and photostable nanoparticles such as quantum dots (QDots) is vastly increasing. One major hurdle that impedes QDot use in live cells and animals is their potential toxicity. Here, we employ a recently described multiparametric setup to determine the concentration at which common polymer-coated QDots become non-cytotoxic. We found that toxic effects are strongly related to the intracellular QDot amount that can be controlled by their specific surface coating. Using lysosomal buffer systems and proliferation-restricted cells, intracellular QDots were found to localize in endosomes, where they generate reactive oxygen species, interfere with cell cytoskeleton and leach free Cd 2+ ions due to QDot dissolution, resulting in increased toxicity and impeded QDot fluorescence. Furthermore, we find that asymmetric partitioning of QDots upon recurrent cell division results in the sacrifice of heavily-loaded cells and a rapid loss of particles in live cells, limiting the use of currently available QDots for long-term imaging and defining the non-cytotoxic concentration as 10-fold lower than commonly used concentrations.
Evaluation of Quantum Dot Cytotoxicity Based on Intracellular Uptake
Small, 2006
Advances in nanomaterials have led to promising candidates for many biological applications in research and medicine. Their novel physicochemical properties, attributable to their small size, chemical composition, surface structure, solubility, and shape, have been increasingly utilized in medicine for purposes of diagnosis, imaging, and drug delivery. Applications range from the fluorescent tracking of cells [1-3] and immunostaining assays [4] to magnetic resonance imaging. [5] Given the potential for widespread application and commercialization, nanomaterials will be increasingly uti-A C H T U N G T R E N N U N G lized for future biological applications. [6] Quantum dots (QDs) are an example of a nanomaterial that possesses optical properties ideal for biological imaging, which makes them a useful alternative to fluorescent dyes. The organic fluorophores currently used are vulnerable to chemical and metabolic degradation and are easily photobleached, which limits long-term cellular tracking. QDs offer advantages, such as bright photoluminescence, narrow emission, broad UV excitation, and high photostability, [7-9] to help overcome current optical-imaging limitations. Due to the tremendous focus on developing nanoparticles for imaging and therapeutic applications, there has been increasing interest in evaluating the toxicity of nanomaterials, [10] in particular, quantum dots. Some studies suggest that nanomaterials are not inherently benign and affect biological systems at the cellular, subcellular, and protein levels. [11-15] Akerman et al. demonstrated that some nanoparticulates are cleared from the circulation of live mice by the macrophages of the reticuloendothelial system in the liver and spleen. [16] Nevertheless, concerns have surfaced regarding the toxicity of QDs, in particular, those nanoparticles that are cadmium-containing and thus toxic to both cell cul
2008
Abstract This study evaluates the influence of particle size, PEGylation, and surface coating on the quantitative biodistribution of near-infrared-emitting quantum dots (QDs) in mice. Polymer-or peptide-coated 64 Cu-labeled QDs 2 or 12 nm in diameter, with or without polyethylene glycol (PEG) of molecular weight 2000, are studied by serial micropositron emission tomography imaging and region-of-interest analysis, as well as transmission electron microscopy and inductively coupled plasma mass spectrometry.
Effect of ligand nature on the kinetics and the bio-distribution of quantum dots in mice
The meeting of nano-materials with biology has produced a new generation of technologies that can profoundly impact biomedical research. The NIR emitting window (650-900 nm) is appealing for in vivo optical imaging because of the low tissue absorption and scattering in this wavelength range. The design of high-quality NIRemitting quantum dots, with outstanding optical properties in comparison to organic dyes, should therefore lead to novel contrast agents with improved performance. Quantum dot growth is controlled by the coordination of hydrophobic ligands. Hence, they have to be transferred in water and conveniently coated before their use in vivo. Several coating strategies are developed. In this paper we report the coating of commercial ITK705-amino particles with methoxy-terminated PEG of different chain length and their in vivo behaviour. Fluorescence imaging studies indicate that the speed of first pass extraction of the coated quantum dots towards the liver depends strongly o...
Effect of Poly(ethylene glycol) Length on the in Vivo Behavior of Coated Quantum Dots
Langmuir, 2009
The use of nanoparticles, either for the delivery of drugs or for imaging contrast agents, or a combination of both (theranostics), is very appealing in biological and biomedical research. The design of high-quality NIR-emitting quantum dots (QDs), with outstanding optical properties in comparison to that of organic dyes, should lead to novel contrast agents with improved performance for optical and multimodal imaging. Moreover, these nanocrystals could also be used for exploring therapeutic applications, such as drug delivery or phototherapy. In this article, we report the coating of commercial ITK705-amino QDs with methoxy-terminated poly(ethylene glycol) (PEG) of different chain lengths. Homogeneous QD solutions that are stable over extended periods of time were prepared. The impact of the particle coating on their in vivo fate after tail IV injection was studied by fluorescence imaging. The speed of the first pass extraction of the coated QDs toward the liver decreased with the PEG length, whereas the hydrodynamic diameter of the particles was increased.
microPET-Based Biodistribution of Quantum Dots in Living Mice
Journal of Nuclear Medicine, 2007
This study evaluates the quantitative biodistribution of commercially available CdSe quantum dots (QD) in mice. Methods: 64 Cu-Labeled 800-or 525-nm emission wavelength QD (21-or 12-nm diameter), with or without 2,000 MW (molecular weight) polyethylene glycol (PEG), were injected intravenously into mice (5.55 MBq/25 pmol QD) and studied using well counting or by serial microPET and region-of-interest analysis. Results: Both methods show rapid uptake by the liver (27.4-38.9 %ID/ g) (%ID/g is percentage injected dose per gram tissue) and spleen (8.0-12.4 %ID/g). Size has no influence on biodistribution within the range tested here. Pegylated QD have slightly slower uptake into liver and spleen (6 vs. 2 min) and show additional low-level bone uptake (6.5-6.9 %ID/g). No evidence of clearance from these organs was observed. Conclusion: Rapid reticuloendothelial system clearance of QD will require modification of QD for optimal utility in imaging living subjects. Formal quantitative biodistribution/imaging studies will be helpful in studying many types of nanoparticles, including quantum dots.
Biochemical and Biophysical Research Communications, 2012
CdSe-core, ZnS-capped semiconductor quantum dots (QDs) are of great potential for biomedical applications. However, applications in the gastrointestinal tract for in vivo imaging and therapeutic purposes are hampered by their sensitivity to acidic environments and potential toxicity. Here we report the use of coatings with a combination of polythiol ligands and silica shell (QDs PolyT-APS) to stabilize QDs fluorescence under acidic conditions. We demonstrated the stability of water-soluble QDs PolyT-APS both in vitro, in strong acidic solutions, and in vivo. The biodistribution, stability and photoluminescence properties of QDs in the gastrointestinal tract of mice after per os administration were assessed. We demonstrated that QDs coated with current traditional materials -mercapto compounds (QDs MPA) and pendant thiol group (QDs PolyT) -are not capable of protecting QDs from chemically induced degradation and surface modification. Polythiol ligands and silica shell quantum dots (QDs PolyT-APS) are suitable for biological and biomedical applications in the gastrointestinal tract.
Journal of Pharmaceutical Investigation, 2012
Tissue distribution and observable-adverseeffect-level of cadmium selenide/cadmium sulfide (CdSe/ CdS) quantum dots (QDs) were investigated to get important information of this QDs. Female BALB/c mice were treated with single intravenous (IV) injection of polyethylene glycol-folic acid-coated QDs (CdSe/CdS-PEG-FA) at different concentrations (0, 270, and 540 pmol/20 g of mice body weight), and the subsequent toxicological effect-levels were examined for 24 h. The health and apparent behaviors of the animals were normal throughout the study. The distribution of the QDs was observed in the spleen, liver, lung and kidneys, but not in the brain and heart tissues. The spleen and liver possess the highest amount of the QDs followed by the lung while the kidneys possess the few. There were no changes in the organ weight index, total protein concentration, LDH activity, and specific NADPH oxidase activity in any tested organ indicating no toxic effects of the QDs in our study. Additionally, histopathological examination did not show any cellular/tissue structural damages. Overall, single IV administration of CdSe/CdS-PEG-FA QDs to BALB/c mice allows immediate systematic availability, and showed different tissue distribution without any obvious toxic effects at our experimental design.