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Systemic siRNA Delivery with Reducible Bile Acid-Modified PEI for Cancer Therapy
김다훤,임수연,김이슬,정재백,김동민,조희주,정지훈 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1
Small interfering RNA (siRNA) delivery has been considered as a potential cancer therapy because it contributes to RNA interference (RNAi) by inhibiting target gene expression in a sequence-specific manner. In this study, low molecular weight polyethylnimine (PEI, 1.8 kDa) was conjugated with deoxycholic acid (DA). A DA-PEI conjugate was further modified with 4-fluorothiophenol (FTP) (TP-DA-PEI) to enhance systemic siRNA delivery. The thiophenol group would be involved with disulfide bonds between the polymer chains and siRNA modified with free thiols (thiol-siRNA) to form and π-π interactions between the pendent aromatic groups and coprostane ring of the bile acid. The stabilized TP-DA-PEI conjugate with thiol-siRNA achieved enhanced intracellular uptake, serum stability, and transfection efficiency. In addition, it showed high accumulation of TP-DA-PEI/ thiol-siRNA polyplexes and significant tumor growth inhibition effect in tumor-bearing mice after systemic administration.