Tumor-binding prodrug micelles of polymer-drug conjugates for anticancer therapy in HeLa cells

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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.
Publisher
ROYAL SOC CHEMISTRY
Issue Date
2012
Language
English
Article Type
Article
Keywords

SELF-ASSEMBLED NANOPARTICLES; FOLATE RECEPTOR; CANCER-CELLS; IN-VITRO; DELIVERY; RELEASE; PHYTOSPHINGOSINE; FABRICATION; TISSUES; AGENTS

Citation

JOURNAL OF MATERIALS CHEMISTRY, v.22, no.18, pp.9385 - 9394

ISSN
0959-9428
DOI
10.1039/c2jm30534h
URI
http://hdl.handle.net/10203/101739
Appears in Collection
CBE-Journal Papers(저널논문)
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