title: Selenium nanoparticles as a carrier of 5-fluorouracil to achieve anticancer synergism.
abstract: 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-O and Se-N 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 IC(50) values ranging from 6.2 to 14.4 μM. 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.
authors: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors: Wen
authors: W
authors: Liu
authors: Xiaoling
authors: X
authors: Li
authors: Yum-Shing
authors: YS
authors: Wong
authors: Wenjie
authors: W
authors: Zheng
authors: Yibo
authors: Y
authors: Zhang
authors: Wenqiang
authors: W
authors: Cao
authors: Tianfeng
authors: T
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D012643:Selenium / Q000008:administration & dosage* / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D012643:Selenium; D005472:Fluorouracil