Tumor-binding prodrug micelles of polymerdrug conjugates for anticancer therapy in HeLa cellsElectronic supplementary information (ESI) available: (1) 1H-NMR spectra of synthesized polymerdrug conjugates (2) IC30 value of various drug formulations, (3) summarized intracellular uptake of DOXPHSM and DOXFOLPHSM, assessed by flow cytometry, (4) low magnification CLSM images of HeLa cells incubated with DOXPHSM and DOXFOLPHSM and subcellular distribution of DOXPHSM and DOXFOLPHSM, trafficked by lyso

• Main Authors: Jung, Bokyung, Jeong, Yong-Cheol, Min, Jun-Hong, Kim, Jung-Eun, Song, Yoon-Jae, Park, Jung-Ki, Park, Jung-Hwan, Kim, Jong-Duk
• Format: Journal Article
• Language: English
• Published: 10.04.2012
• ISSN: 0959-9428; 1364-5501
• DOI: 10.1039/c2jm30534h

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 polymerdrug conjugates wherein hydrophobic PHS was connected to the folate-grafted hydrophilic and biocompatible polymer through pH-sensitive linkages. The polymerdrug conjugates formed nano-sized (1020 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. Tumor-binding polymerdrug conjugates with hydrophobic phytosphingosine connected to folate-grafted hydrophilic and biocompatible polymers are presented.