Cyto-/Genotoxic Effect of CdSe/ZnS Quantum Dots in Human Lung Adenocarcinoma Cells for Potential Photodynamic UV Therapy Applications
Cyto-/Genotoxic Effect of CdSe/ZnS Quantum Dots in Human Lung Adenocarcinoma Cells for Potential Photodynamic UV Therapy Applications
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DOI：
10.1166/jnn.2012.5781
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发表时间：
2012-03-01
影响因子：
--
通讯作者：
Chung, Hai Won
中科院分区：
文献类型：
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作者：
Choi, Young Joo;Kim, Yang Jee;Chung, Hai Won
量子点（QDs）是一种发光纳米粒子（NPs），在许多医学应用中具有广阔的潜力，但仍存在持续的人类健康和安全问题。虽然量子点的细胞毒性作用已被广泛研究，但其遗传毒性作用仍未得到充分探讨。本研究考察了硒化镉/硫化锌（CdSe/ZnS）核/壳量子点的细胞毒性和基因毒性效应，并为量子点在癌症治疗中的应用提出了综合指南。利用量子点对A549细胞进行了UVA/UVB（紫外线A/B）照射和不照射处理。通过3-（4,5-二甲基噻唑-2-酰基）-2,5-二苯基溴化四唑（MU）、细胞凋亡和乳酸脱氢酶（LDH）检测，以及实时PCR分析参与细胞凋亡的基因差异mRNA水平，如失调性毛细血管扩张突变（ATM）、p53和caspase-9。本文首次采用彗星和微核方法测定了CdSe/ZnS量子点在人癌细胞中的遗传毒性作用。CdSe/ZnS量子点和UVB照射导致的细胞死亡程度最严重，表明CdSe/ZnS量子点在UVB存在下具有很强的光毒性。QDs和UVB联合治疗可观察到凋亡和坏死细胞死亡。当CdSe/ZnS量子点和UVB联合照射时，橄榄尾力矩和微核形成的诱导作用也最为显著。我们对CdSe/ZnS量子点诱导细胞死亡的基因毒性效应和机制细节的研究结果表明，在光动力癌症治疗中，UVB照射是提高量子点效力的最有效方法。
Quantum dots (QDs) are luminescent nanoparticles (NPs) with promising potential in numerous medical applications, but there remain persistent human health and safety concerns. Although the cytotoxic effects of QDs have been extensively investigated, their genotoxic effects remain under-explored. This study scrutinized the cyto- and genotoxic effects of QDs with a Cadmium selenide/Zinc sulfide (CdSe/ZnS) core/shell, and suggests comprehensive guidelines for the application of QDs in cancer therapy. QDs were used to treat A549 cells in the presence and absence of ultraviolet A/B (UVA/UVB) irradiation. OD-induced cell death was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MU), apoptosis, and lactate dehydrogenase (LDH) assays, as well as by real-time PCR analysis of differential mRNA levels of genes, such as ataxia telangiectasia mutated (ATM), p53, and caspase-9, involved in apoptosis. The genotoxic effect of CdSe/ZnS QDs was measured in human cancer cells, for the first time, by comet and micronucleus assays. Treatment with CdSe/ZnS QDs and UVB irradiation resulted in the most severe extent of cell death, indicating strong induction of phototoxicity by CdSe/ZnS QDs in the presence of UVB. Both apoptotic and necrotic cell death were observed upon QDs and UVB combined treatment. The induction of Olive tail moments and micronuclei formation was also most significant when CdSe/ZnS QDs and UVB irradiation were combined. Our results on the genotoxic effect and mechanistic details of CdSe/ZnS QD-induced cell death suggest that UVB irradiation is the most effective method for increasing the potency of QDs during photodynamic cancer therapy.