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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.
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Self-citation
Metadata
- Authors
- Liu, W., Li, X., Wong, Y.-S., Zheng, W., Zhang, Y., Cao, W., & Chen, T.
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-07-26
- Volume
- 6
- Issue
- 8
- Pages
- 6578-6591
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2010240044
- Cited by
- 349
- References
- 38
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- closed
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