Fabrication of chitosan-based nanoparticles as a dual-functional drug carrier in combinational chemo-photodynamic therapy

• Main Authors: Chang, Yu Cheng, 張祐誠
• Other Authors: Huang, Yu Fen
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/60693061910011549235

碩士 === 國立清華大學 === 生醫工程與環境科學系 === 103 === Dual functional drug carrier has been a modern strategy in cancer therapy, because it is a platform to evaluate synergistic effect through combination therapy. In the present study, we combined properties of two drugs Paclitaxel (PTX) and Rose Bengal (RB) as a synergistic treatment of chemo-photodynamic therapy . In order to encapsulate these hydrophobic and hydrophilic drugs in one functional system, we fabricate polymeric nanocarriers (NCs) using tripolymer mixtures of chitosan (CTS), branched polyethylenimine (bPEI) and polyvinyl alcohol (PVA) through an oil-in-water emulsion method. The polycationic properties of CTS and bPEI permit effective entrapment of RB molecules. During assembly process, bovine serum albumin (BSA) was also added to condense cationic tripolymer mixtures into stable nanocarriers (BNCs). Eventually, hyaluronic acid (HA) was used as an ionic cross-linking agent through electrostatic interaction to lower down carrier’s zeta potential for suitable application in biological systems. Our results suggest an effective drug loading and high dispersion stability of HBNCs in different buffer solutions. Low leakage of drug molecules from the engineered HBNCs were also confirmed on the basis of dialysis experiments. Moreover, fluorescence microscopic images displayed a high intracellular uptake and localization of drug-loaded HBNCs toward Tramp-C1 cells. The photodynamic effect showed intracellular RB release after photo irradiation; its ROS generation was further evaluated by flow cytometry and alamar blue cytotoxicity assays. Together, our dual-drug carrier system assures enhanced cytotoxicity in cancer cells compared with single-loading drug alone. A dual-functional delivery platform was successfully established to improve the therapeutic efficacy in tumor cells.