Copolymer of poly(ethylene glycol) and poly(L-lysine) grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery

摘要: siRNA therapy research has primarily focused on the synthesis and development of effective delivery vectors with easy biodegradability low toxicity. In present study, we synthesized a ternary copolymer mPEG-b-PLL-g-(ss-lPEI), denoted as PLI, by introducing disulfide bond linkages to graft molecular weight linear polyethylenimine (lPEI) block poly(L-lysine) (PLL) poly(ethylene glycol) (PEG) for delivery. The PLL linkage rendered carrier biodegradability, while lPEI grafting brought about proton buffering capacity lysosomal release cationic Conjugation single chain monoclonal antibody (Herceptin) targeting ligand Her2/neu receptor significantly increased transfection activity copolymer/siRNA nanocomplex (i.e. polyplex) in Skov-3, human ovarian cancer cell line. Determination gene expression at both mRNA protein levels demonstrated that Her2-targeted (XIAP siRNA) effectively downregulated targeted XIAP (X-linked inhibitor apoptosis protein) gene, resulting enhanced improved therapeutic efficacy vitro vivo. distinct features cytotoxicity, degradability, high efficiency make promising candidate tumors.