利用光致產酸劑調控pH應答型高分子微胞於藥物釋放及抑制癌細胞生長之研究

• Main Authors: WANG,TUNG-YUN, 王彤云
• Other Authors: Chen, Ching-Yi
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/6gj3s7

碩士 === 國立中正大學 === 化學工程研究所 === 104 === Nanocarriers as drug delivery systems have become an emerging research area for cancer therapy in recent years. Intelligent materials that respond to a specific stimulus, such as pH, temperature or enzymatic activity have been attracted great attention. In this study, we developed a series of pH-responsive amphiphilic block copolymers, namely poly(ethylene glycol)-b-poly(2-(di- isopropylamino)ethyl methacrylate) (mPEG-b-PDPA) via atom transfer radical polymerization. The purity and molecular weight of the synthesized copolymers were fully characterized by 1H NMR spectra and GPC. The mPEG-b-PDPA copolymer can self-assemble to form micelles in aqueous medium. The pH-responsive and hydrophobic DPA segment was used to encapsulate hydrophobic photoacid generators (PAG) and anticancer drug (doxorubicin, DOX) in the micellar core. PAG can be photo-triggered to generate strong acid, which was utilized for controlling drug release. Herein, we adjusted the length of DPA segment to control the pH-sensitivity of micelles under light-triggering. After UV light irradiation, the pH values of micellar solution decreased from 6.8 to 5.2 and the size distribution of PAG-loaded micelles also became broad. These results indicated the generation of strong acid due to light-triggered PAG which protonated the DPA segment and changed the micellar structure. In vitro drug release study showed the faster release rate after light irradiation compared with that without irradiation, indicating light-triggered PAG faciliated the release of the encapsulated drug. In vitro cytotoxicity study showed the blank micelles have good biocompatibility. The cell viability treated with PAG/DOX loaded micelles decreased to 20 % after light irradiation, however, those treated with individual PAG or DOX loaded micelles, or PAG/DOX loaded micelles without light irradiation showed cell viability of more than 85 %. This result proved that our PAG/DOX loaded micelles can effectively inhibit the growth of the cancer cell by light triggering PAG.