Journal
JOURNAL OF MATERIALS CHEMISTRY
Volume 22, Issue 18, Pages 9385-9394Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2jm30534h
Keywords
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Funding
- Ministry of Science and Technology of the Korean government [2010-0018769]
- Gachon University
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An interesting phytosphingosine (PHS), a natural sphingolipid metabolite comprising ceramides, is believed to play a vital role in strong anticancer therapeutic efficacy for various types of cancer cells, which is based on a programmed cellular death mechanism, so called apoptosis. However, extremely low water-solubility has been an obstacle to its usage as an anticancer drug via the systemic administration route. To utilize the benefits of PHS, we developed tumor-targeting polymer-drug conjugates wherein hydrophobic PHS was connected to the folate-grafted hydrophilic and biocompatible polymer through pH-sensitive linkages. The polymer-drug conjugates formed nano-sized (10-20 nm) spherical micelles spontaneously in aqueous media and they were found to have high drug contents (10.3 wt%). We present a systematic study of in vitro anticancer therapy in HeLa cells treated by tumor-targeting micelles in terms of anti-proliferation. The anticancer effect was analyzed by apoptotic cell death as well as the preferential distribution of loaded drug in the cancer cells. The synergistic effect by loading the commercial drug of doxorubicin was also studied.
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