| Summary: | 碩士 === 國立中正大學 === 化學工程研究所 === 105 === Chemotherapy in cancer treatment is often limited by the toxicity of the anti-cancer drugs used. This is because both cancer cells and normal cells are non-selectively for the anti-cancer drugs. Besides, some anti-cancer drugs are hydrophobic that leads drugs to aggregate and be rapidly excreted from human body and reduce the therapeutic efficiency of drugs. To improve these weaknesses, we designed a new delivery system formed by amphiphilic block copolymers. In our study, we selected two materials, one is hydrophilic 2-(methacryloyloxy) ethyl phosphoryl-choline (MPC) which has good biocompatibility and the ability to resist the adsorption of proteins, and the other is hydrophobic ε-caprolactone (CL) which has biodegradability. First, we synthesized poly (ε-caprolactone) (PCL) via ring-opening polymerization, and then synthesized a series of amphiphilic block copolymers via atom transfer radical polymerization. Furthermore, to introduce targeting function for the delivery carriers, click chemistry strategy was utilized to function the folic acid at the end of segment of the PMPC：FA-PMPC-b-PCL (FMP). The 1H NMR, FTIR and GPC were used to identify the structure and molcular weight of these copolymers.
The prepared amphiphilic block copolymers were used to encapsulate hydrophobic drugs, curcumin (CUR). The sizes of curcumin loaded micelles determined by DLS were about 180-260 nm. And the best loading content of FMP-B micelles could reach 3.60 %. In-vitro drug release study, the curcumin loaded micelles were found at 37℃ in acidic condition (pH 5) the accumulation of drug could reach about 80 %.
The cytotoxicity of blank micelles were tested against cervical cells (HeLa cells) with overexpressive folate receptors. The result of MTT assay showed that the cell viability of blank micelles were above 90 %, which proved the blank micelles had good biocompatibility. The result of competitive test showed the IC50 of FMP-B with free FA (21.3 mg/mL) was higher than the IC50 of FMP-B without free FA (12.3 mg/mL). It confirmed FMP micelles had the target property.
To verify the photosensitivity of curcumin, we used ROS indicator to detect the generation of ROS via Laser Scanning Confocal Microscopy. The result showed FMP-B generated ROS after illumination. We also tested the phototoxicity of CUR. The cell viability of FMP-B without irradiation could reach 60 %.However, the cell viability of FMP-B decreased to 40 % and 30 % with 5 or 10 min irradiation, respectively. It proved that curcumin had cytotoxicity in darkness and FMP-B micelles had photodynamic therapy efficacy under irradiation. Finally, we verified that the amphiphilic block copolymer as drug carriers to encapsulate CUR could be applied for anti-tumor and photodynamic therapy.
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