| Summary: | 碩士 === 國立陽明大學 === 醫學工程研究所 === 102 === α-Tocopheryl succinate (α-TOS), an analogue of vitamin E, can induce apoptosis in cancer cells, while exhibiting low toxicity in normal cells. In this study, the block copolymer, methoxy poly(ethylene glycol)-block-poly (hydroxypropyl methacrylate) (mPEG-b-PHPMA) was designed as the hydrophilic main chain. The hydrophobic α-TOS and pH-sensitive histidine were grafted onto the block copolymer by coupling reaction, forming comb-like copolymer, mPEG-b-P(HPMA-g-α-TOS-g- His). The copolymers were self-assembled into polymeric micelles which loaded with both anticancer drug, doxorubicin, and apoptosis-induced agent, α-TOS.
According to the measurement of dynamic laser scanning (DLS), the particle size of the polymeric micelles was 166.0±29.6 nm and the polydispersity index (PDI) was 0.157±0.007. The drug release profiles showed that the histidine-contained polymeric micelles (P-T-His) exhibited excellent pH-sensitivity. In vitro study indicated that the polymeric micelles P-T-His exhibited very low cytotoxicity to mouse fibroblast cells L929 as well as human colon cancer cell HCT116. Dual drug loaded micelles could effectively inhibit cancer cell proliferation. The results of flow cytometry indicated that P-T-His micelles could be uptaken into colon cancer HCT116 cells. In vivo study has showed that the dual drug-loaded micelles preferentially accumulated in tumor tissues. In summary, the P-T-His micelles encapsulated with α-TOS and Dox possessed the potential for anticancer therapy.
Keywords: α-tocopheryl succinate; histidine; pH-sensitive micelles
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