具酸鹼應答性複合型高分子微胞於光動力治療 合併化學療法上之應用

• Main Authors: Syu,Chao-Kai, 許朝凱
• Other Authors: Chen,Ching-Yi
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/gh25df

碩士 === 國立中正大學 === 化學工程研究所 === 102 === Cancer therapy has been always the important object in the field of biomedical research. Many attentions have been dedicated on improving therapeutic efficacy, which relys on only a single modality. Currently, combination therapy has emerged as a promising strategy in oncology, such as combination of photothermal and chemotherapy or photodynamic and chemotherapy. To ensure both therapeutic agents could be simultaneously accumulated within solid tumor and exert their synergistic effect, a safe and intelligent delivery system is highly demanded. In this study, we developed a series of pH-sensitive block copolymers, poly(ethylene glycol) methyl ether - block – poly(2-(diisopropylamino)ethyl methacrylate) (mPEG-b-PDPA) via atom transfer radical polymerization. In addition, click reaction was applied for modifying the insoluble photosensitizer zinc tetra(progaryloxyphenyl)porphyrin with poly(ethylene glycol) (Star-PEG-ZnTPP). 1H﹣NMR and GPC were used to characterize their chemical structures, purity and molecular weight. The mixed micelles were prepared by self-assembly from different weight ratios of mPEG-b-PDPA and Star-PEG-ZnTPP in an aqueous environment and further to encapsulate the anticancer drug doxorubicin (Dox) for combination therapy. The optimized mixed micelles (M2) show the average diameter of 122.3 ±5.1 nm by dynamic light scattering and good stability. Under light irradiation, ZnTPP can transfer its energy to surrounding oxygen to generate cytotoxic singlet oxygen, indicating our mixed micelles have the capability for photodynamic therapy. At neutural condition, the mixed micelles show a slower release rate than that of acid, indicating that the micelles are more stable in neutural condition, and at acidic condition the drugs release fast, so that they can be used in controlled drug release system . The cytotoxicity of blank M2 was tested against a cancer cell line, HeLa cells. No significant cytotoxicity was observed, indicating our mixed micelles have good biocompatibility. The cytotoxicity and phototoxicity of Dox-loaded M2 micelles showed significant improvement on the cytotoxicity of Dox in HeLa celles after irradiation. This result demonstrated our new mixed polymer micelles integrated with chemotherapy and photodynamic therapy can enhance the efficiency for the treatment of cancer.