- 學位論文
開發與評估新一代結合光動力及化學療法之載體
Multifunctional chlorin- centered micelles for chemotherapy and photodynamic therapy in human cancer
並列摘要
To improve its aqueous solubility and stability in biological fluid, paclitaxel was physically loaded in polymeric micelles. For the other purpose, polymeric micelles were made to be a kind of photosensitizer conjugates composed of various Methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) diblock copolymers (MPEG-PCL) and chlorin. The chemical structure of novel copolymers and paclitaxel-loading efficiency were measured by using 1H NMR gel permeation chromatography (GPC) and HPLC. A stable formulation of paclitaxel-loaded micelles was only manufactured by using chlorin-core MPEG-PCL copolymer (M58C, M.W. = 52000). MPEG-PCL diblock copolymers were synthesized via the typical process of polymerization of CL using the terminal alcohol of MPEG (Mn, 5000 g/mol) with different PCL molecular weight. The loading efficiency of micelles was about 80% at D/P ratio of 0.02. It was seen that the activity in inhibiting the growth of HT-29 cells (a colon caner line) by the paclitaxel-loaded micelles was comparable to that of free paclitaxel in dark experiments, while paclitaxel-loaded micelles showed less activity. Confocal data also showed the paclitaxel-loaded micelles had the same effect on microtubules of HT-29 and MCF-7(a breast cancer cell lines) as paclitaxel. In light experiments, the carriers didn’t show significant PDT effect because of not enough singlet oxygen produced to kill cells. But, carriers caused more cell death in PDT and CT experiments than only in PDT experiments. In conclusion, the chlorin-core micelles, provided with PDT effect, may be used as a potential drug delivery system for paclitaxel (chemotherapeutic drug) in the future clinically.
參考文獻
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