Selenium Nanoparticles as a Carrier of 5-Fluorouracil to Achieve Anticancer Synergism
详细信息 查看全文
- 作者：Wen Liu ; Xiaoling Li ; Yum-Shing Wong ; Wenjie Zheng ; Yibo Zhang ; Wenqiang Cao ; Tianfeng Chen
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：August 28, 2012
- 年：2012
- 卷：6
- 期：8
- 页码：6578-6591
- 全文大小：1737K
- 年卷期：v.6,no.8(August 28, 2012)
- ISSN：1936-086X
文摘
A simple method for preparing 5-fluorouracil surface-functionalized selenium nanoparticles (5FU-SeNPs) with enhanced anticancer activity has been demonstrated in the present study. Spherical SeNPs were capped with 5FU through formation of Se鈥揙 and Se鈥揘 bonds and physical adsorption, leading to the stable structure of the conjugates. 5FU surface decoration significantly enhanced the cellular uptake of SeNPs through endocytosis. A panel of five human cancer cell lines was shown to be susceptible to 5FU-SeNPs, with IC50 values ranging from 6.2 to 14.4 渭M. Despite this potency, 5FU-SeNP possesses great selectivity between cancer and normal cells. Induction of apoptosis in A375 human melanoma cells by 5FU-SeNPs was evidenced by accumulation of sub-G1 cell population, DNA fragmentation, and nuclear condensation. The contribution of the intrinsic apoptotic pathway to the cell apoptosis was confirmed by activation of caspase-9 and depletion of mitochondrial membrane potential. Pretreatment of cells with a general caspase inhibitor z-VAD-fmk significantly prevented 5FU-SeNP-induced apoptosis, indicating that 5FU-SeNP induced caspase-dependent apoptosis in A375 cells. Furthermore, 5FU-SeNP-induced apoptosis was found dependent on ROS generation. Our results suggest that the strategy to use SeNPs as a carrier of 5FU could be a highly efficient way to achieve anticancer synergism. 5FU-SeNPs may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially melanoma.