An in vitro study of vascular endothelial toxicity of CdTe quantum dots

Yan, Ming; Zhang, Yun; Xu, Kedi; Fu, Tao; Qin, Haiyan; Zheng, Xiaoxiang

doi:10.1016/j.tox.2011.01.015

Cited by 115 publications

(80 citation statements)

References 54 publications

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“…QDs induce the generation of reactive oxygen species, 50 which leads to detrimental autophagic cell death or necrosis [51][52][53] or which activates intrinsic mitochondrial apoptotic pathways. 21 It is known that smaller QDs penetrate deeper into cells and induce toxicity at far quicker rates than their larger counterparts. However, in our studies, QD4.7 was found to be comparatively more cytotoxic than QD2.7, which could be attributed to either the higher negative charge on the surface or to their preferential accumulation in the cytoplasm, thereby triggering different or additional toxicity mechanisms.…”

Section: Figurementioning

confidence: 99%

“…Another class of NPs is presented by semiconductor quantum dots (QDs), which possess unique optoelectronic properties such as tunable narrow emission spectra, high quantum yields, broad absorption spectra, and high resistance to photobleaching. 21 QDs are successfully used in biomedicine as labeling agents for imaging biological molecules, cells, and even tissues 22 or to trace drug molecules in live organisms. 23,24 However, for biological applications, QDs must be surface passivated with other materials to allow for dispersion and to prevent the leakage of toxic heavy metals.…”

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confidence: 99%

“…29 A systematic study of the mechanisms of interaction of nonfunctionalized CdTe and CdSe/ZnS QDs with a panel of live human cells of different origin has demonstrated that the nonfunctionalized QDs exploit the cell's active transport machineries for intranuclear delivery. 30 The effects of NPs such as carbon black, 31 silver, 32 metal oxides, 33 MgO, 34 SiO 2 , 35 QDs, 21 and polymeric NPs 19 on ECs have been studied under static conditions. However, no comprehensive study has been undertaken to evaluate the interaction of engineered NPs on human ECs under varying flow conditions.…”

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confidence: 99%

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Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

Samuel¹,

Jain²,

O'Dowd³

et al. 2012

IJN

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Vascular endothelium is a potential target for therapeutic intervention in diverse pathological processes, including inflammation, atherosclerosis, and thrombosis. By virtue of their intravascular topography, endothelial cells are exposed to dynamically changing mechanical forces that are generated by blood flow. In the present study, we investigated the interactions of negatively charged 2.7 nm and 4.7 nm CdTe quantum dots and 50 nm silica particles with cultured endothelial cells under regulated shear stress (SS) conditions. Cultured cells within the engineered microfluidic channels were exposed to nanoparticles under static condition or under low, medium, and high SS rates (0.05, 0.1, and 0.5 Pa, respectively). Vascular inflammation and associated endothelial damage were simulated by treatment with tumor necrosis factor-α (TNF-α) or by compromising the cell membrane with the use of low Triton X-100 concentration. Our results demonstrate that SS is critical for nanoparticle uptake by endothelial cells. Maximal uptake was registered at the SS rate of 0.05 Pa. By contrast, endothelial exposure to mild detergents or TNF-α treatment had no significant effect on nanoparticle uptake. Atomic force microscopy demonstrated the increased formation of actin-based cytoskeletal structures, including stress fibers and membrane ruffles, which have been associated with nanoparticle endocytosis. In conclusion, the combinatorial effects of SS rates, vascular endothelial conditions, and nanoparticle physical and chemical properties must be taken into account for the successful design of nanoparticle-drug conjugates intended for parenteral delivery. Keywords: endothelium, shear stress, quantum dots, membrane ruffling, stress fibers, atomic force microscopy, microfluidics Nanoparticle (NP) technologies are significantly affecting the development of both therapeutic and diagnostic agents. Although enormous progress in the field of nanotechnology has been achieved, basic discoveries have not yet translated into effective targeted therapies. NPs can potentially improve the pharmacokinetics and pharmacodynamics of drugs; however, the complexity of in vivo systems imposes multiple barriers that severely inhibit efficiency, which must be overcome to fully exploit the theoretical potential of NPs. Endothelial cells (ECs) that line the interior of the entire vascular system represent a major barrier for therapeutic agents traveling from the bloodstream to the target tissues. Recent studies have focused on targeting the endothelium with NPs as therapeutic agents for a variety of pathological conditions in the vascular system because of the large population of ECs and their proximity to the blood flow.ECs in vivo are exposed to a variety of hemodynamic forces that are created by blood flow and by the pulse wave dictated by the cardiac cycle. Shear stress (SS) is the dragging mechanical force that acts at the interface between flowing blood and Dovepress submit your manuscript | www.dovepress.com the vessel wall. ECs recognize SS a...

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Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

Samuel¹,

Jain²,

O'Dowd³

et al. 2012

IJN

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“…Previous studies have demonstrated the toxicity of CdTe QDs in mammalian cells [6][7][8] and revealed that this toxicity is dependent on their physicochemical properties, such as size, charge, concentration, and outer coating. 9 It has been suggested that the toxicity of CdTe QDs is related to oxidative stress, which can lead to lysosome enlargement, 8 mitochondrial network fragmentation, 7 and activation of autophagy.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of autophagy contributes to the toxicity of cadmium telluride quantum dots in <em>Saccharomyces cerevisiae</em>

Fan¹,

Shao²,

Lai³

et al. 2016

IJN

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Cadmium telluride quantum dots (CdTe QDs) are used as near-infrared probes in biologic and medical applications, but their cytological effects and mechanism of potential toxicity are still unclear. In this study, we evaluated the toxicity of CdTe QDs of different sizes and investigated their mechanism of toxicity in the yeast Saccharomyces cerevisiae . A growth inhibition assay revealed that orange-emitting CdTe (O-CdTe) QDs (half inhibitory concentration [IC 50 ] =59.44±12.02 nmol/L) were more toxic than green-emitting CdTe QDs (IC 50 =186.61±19.74 nmol/L) to S. cerevisiae . Further studies on toxicity mechanisms using a transmission electron microscope and green fluorescent protein tagged Atg8 processing assay revealed that O-CdTe QDs could partially inhibit autophagy at a late stage, which differs from the results reported in mammalian cells. Moreover, autophagy inhibited at a late stage by O-CdTe QDs could be partially recovered by enhancing autophagy with rapamycin (an autophagy activator), combined with an increased number of living cells. These results indicate that inhibition of autophagy acts as a toxicity mechanism of CdTe QDs in S. cerevisiae . This work reports a novel toxicity mechanism of CdTe QDs in yeast and provides valuable information on the effect of CdTe QDs on the processes of living cells.

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“…The large surface area exhibited by QDs enables them to be functionalised with biocompatible and specific ligands for site-specific activity [1,[4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

UV-enhanced toxicity of water-stable quantum dots in human pancreatic carcinoma cells

Bailón-Ruiz

Perales-Pérez

2013

Journal of Experimental Nanoscience

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Zn-based (capped with thioglycolic acid (TGA) or 3-mercaptopropionic acid (MPA)) and Cd-based quantum dots (QDs) (capped with TGA or L-glutathione), were synthesised and used to investigate their cytotoxicity to human pancreatic carcinoma cells (PANC-1) in absence and presence of UV irradiation. Zn-based QDs exhibited less intrinsic cytotoxicity than the Cd-based QDs, however, the excitation of 50 mg/mL-QDs using UV lamp significantly enhanced the cytotoxicity of both QDs. After 15 min of UV irradiation, the viability for cells exposed to Cd-based QDs capped with TGA or glutathione was 49% AE 6% or 56% AE 3%, respectively. The corresponding cell viability in the control test was 83% AE 8% after 15 min of UV irradiation. In turn, the viability for cells exposed to Zn-based QDs capped with 3-MPA or TGA was 64% AE 3% and 52% AE 3%, respectively, after 30 min of UV irradiation; the cell viability in the control test was 80% AE 7% for the same UV irradiation time. Laser scanning confocal analyses evidenced that QDs can be easily ingested by PANC-1. Based on their good compositional stability, Zn-based QDs capped with 3-MPA can be considered a promising material for nanomedicine applications until concentrations of 200 mg/mL.

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An in vitro study of vascular endothelial toxicity of CdTe quantum dots

Cited by 115 publications

References 54 publications

Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

Inhibition of autophagy contributes to the toxicity of cadmium telluride quantum dots in <em>Saccharomyces cerevisiae</em>

UV-enhanced toxicity of water-stable quantum dots in human pancreatic carcinoma cells

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