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利用微胞複體以光觸發核心破裂的方式促進小干擾核糖核酸釋放
Thesis

利用微胞複體以光觸發核心破裂的方式促進小干擾核糖核酸釋放

陸泓勳
Masters, 國立清華大學, 化學系
2015

Abstract

光觸發斷鍵 奈米微胞 小干擾核醣核酸 基因載體 微胞複體 光響應基因釋放 Photo-triggered bond cleavage Micelle Small-interfering RNA Gene vectors Micelleplexes Photo-triggered gene release
Small-interfering RNA (siRNA), an efficacious manner of RNA interference (RNAi) for gene therapy, furnishes a considerable strategy for cancer treatment by silencing the targeted message RNA (mRNA). Though cationic polymer materials could protect the siRNA through electrostatic interaction from leakage and degradation in the extracellular condition, the low mRNA knockdown efficiency of gene carrier is always hampered by the insufficient capability to release siRNA in cytoplasm. To address the dilemma, herein I developed the PEG-b-PDMAEMA-b-PPy triblock copolymer micelleplexes that could protect siRNA from leakage in physiological condition and respond to photo-stimulus for boosting siRNA release in a spatiotemporal manner. The siRNA release studies of PEG113-b-PDMAEMA31-b-PPy30 micelleplexes demonstrated in heparin that induces instability of gene carriers manifested 15% accumulative release of siRNA after 10 hours in PBS (pH= 7.4, ionic strength= 0.14 M) without UV-irradiation. Meanwhile, the accumulative release of siRNA from micelleplexes triggered by UV-irradiation for 10 minutes was around 40% after 10 hours incubation. The photoresponsive core-shattering micelleplexes equipped with enhanced stability and triggered release would provide a new platform for systemic gene delivery.

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