Choi Young Joo, Kim Yang Jee, Lee Joong Won, Lee Younghyun, Lim Yong-Beom, Chung Hai Won
School of Public Health and Institute of Health and Environment, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
J Nanosci Nanotechnol. 2012 Mar;12(3):2160-8. doi: 10.1166/jnn.2012.5781.
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. QD-induced cell death was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 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.
量子点(QDs)是发光纳米颗粒(NPs),在众多医学应用中具有广阔的潜在应用前景,但仍然存在持续的人类健康和安全问题。尽管量子点的细胞毒性作用已得到广泛研究,但其遗传毒性作用仍未得到充分探索。本研究仔细审查了具有硒化镉/硫化锌(CdSe/ZnS)核壳结构的量子点的细胞毒性和遗传毒性作用,并提出了量子点在癌症治疗中应用的综合指南。在有和没有紫外线A/B(UVA/UVB)照射的情况下,使用量子点处理A549细胞。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)、凋亡和乳酸脱氢酶(LDH)测定,以及通过实时PCR分析参与凋亡的基因(如共济失调毛细血管扩张症突变基因(ATM)、p53和半胱天冬酶-9)的差异mRNA水平,来评估量子点诱导的细胞死亡。首次通过彗星试验和微核试验在人类癌细胞中测量CdSe/ZnS量子点的遗传毒性作用。用CdSe/ZnS量子点和UVB照射处理导致最严重程度的细胞死亡,表明在UVB存在下CdSe/ZnS量子点强烈诱导光毒性。在量子点和UVB联合处理后观察到凋亡和坏死性细胞死亡。当CdSe/ZnS量子点和UVB照射联合使用时,橄榄尾矩的诱导和微核形成也最为显著。我们关于CdSe/ZnS量子点诱导细胞死亡的遗传毒性作用和机制细节的结果表明,UVB照射是在光动力癌症治疗期间提高量子点效力的最有效方法。