Mechanisms underlying toxicity induced by CdTe quantum dots determined in an invertebrate model organism

Ambrosone, Alfredo; Mattera, Lucia; Marchesano, Valentina; Quarta, Alessandra; Susha, Andrei S.; Tino, Angela; Rogach, Andrey L.; Tortiglione, Claudia

doi:10.1016/j.biomaterials.2011.11.041

Cited by 112 publications

(110 citation statements)

References 67 publications

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“…The reduction in cell spreading correlates well with the onset of ROS, suggesting a possible influence of ROS in the cytoskeletal deformations. However, previous data have suggested the conjoined effects of multiple mechanisms to play a role in cell deformations, including 1) the endosomal localization of QDots resulting in enlarged lysosomal compartments [30] and 2) a loss of lysosomal functionality, resulting in large compartments containing high numbers of rigid NPs and hereby occupying a substantial part of the cellular cytoplasmic compartment, sterically hindering normal cytoplasmic functionality [36].…”

Section: Effects Of Qdot Degradation On Cell Viabilitymentioning

confidence: 99%

“…Owing to these properties, QDots have shown great potential for many biomedical applications, including cell labeling applications [18][19][20][21], long-term tracking of (single) molecules [22], in vivo imaging [23,24] and photodynamic therapy [25,26]. However, despite their excellent photophysical properties, their toxicity, in particular due to the release of Cd 2+ ions [27,28], remains an issue of debate [29,30].…”

Section: Introductionmentioning

confidence: 99%

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The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

et al. 2014

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Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, poly(methacrylic acid)-coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at nontoxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticles concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison.

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Section: Effects Of Qdot Degradation On Cell Viabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

et al. 2014

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“…Cadmium, Cd; Indium, In) release from semiconductor nanocrystals may severely limit the use of QDs for biomolecule delivery. It is well documented, in fact, that capped and uncapped nanocrystals undergo degradation producing harmful effects in vitro and in vivo [186][187][188][189].…”

Section: The Fate Of Inorganic Nanovectors For Gene Silencingmentioning

confidence: 99%

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

et al. 2015

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RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells; opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the "do's and dont's" of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 2 inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. *Manuscript Click here to view linked References

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“…[11][12][13] At high levels of oxidative stress, the antioxidant defense system is overwhelmed by the excessive ROS, which eventually leads to mitochondrial malfunction and ultimately cell death. 14 However, in contrast to the sufficient number of QD-cytotoxicity studies, only a few in vivo studies have been reported, 15,16 and the results of these studies are rather inconsistent, due to the wide variation in both and the types of QDs (in terms of size, shape, surface charge, and surface coverage) that have been tested and the animal models in which they have been tested. For example, King-Heiden et al and Truong et al studied QD toxicity in zebrafish and showed that the toxicity was influenced by the QD coating and surface ligands.…”

Section: Introductionmentioning

confidence: 99%

Time-dependent toxicity of cadmium telluride quantum dots on liver and kidneys in mice: histopathological changes with elevated free cadmium ions and hydroxyl radicals

Wang

Sun

et al. 2016

IJN

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A complete understanding of the toxicological behavior of quantum dots (QDs) in vivo is of great importance and a prerequisite for their application in humans. In contrast with the numerous cytotoxicity studies investigating QDs, only a few in vivo studies of QDs have been reported, and the issue remains controversial. Our study aimed to understand QD-mediated toxicity across different time points and to explore the roles of free cadmium ions (Cd 2+ ) and hydroxyl radicals (·OH) in tissue damage. Male ICR mice were administered a single intravenous dose (1.5 µmol/kg) of CdTe QDs, and liver and kidney function and morphology were subsequently examined at 1, 7, 14, and 28 days. Furthermore, ·OH production in the tissue was quantified by trapping · OH with salicylic acid (SA) as 2,3-dihydroxybenzoic acid (DHBA) and detecting it using a high-performance liquid chromatography fluorescence method. We used the induction of tissue metallothionein levels and 2,3-DHBA:SA ratios as markers for elevated Cd 2+ from the degradation of QDs and ·OH generation in the tissue, respectively. Our experimental results revealed that the QD-induced histopathological changes were time-dependent with elevated Cd 2+ and ·OH, and could recover after a period of time. The Cd 2+ and ·OH exhibited delayed effects in terms of histopathological abnormalities. Histological assessments performed at multiple time points might facilitate the evaluation of the biological safety of QDs.

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Mechanisms underlying toxicity induced by CdTe quantum dots determined in an invertebrate model organism

Cited by 112 publications

References 67 publications

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

Time-dependent toxicity of cadmium telluride quantum dots on liver and kidneys in mice: histopathological changes with elevated free cadmium ions and hydroxyl radicals

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