title: Bioreducible polymer-delivered siRNA targeting human telomerase reverse transcriptase for human cancer gene therapy.
abstract: The success of siRNA therapeutics for cancer therapy largely depends on the delivery carrier that can safely and efficiently escort siRNA from the extracellular environment into the targeted human cancer cells. Over the past few years, disulfide-containing (bioreducible) cationic polymers have been designed, prepared and successfully applied as nonviral carriers for powerful gene/siRNA transfer, meanwhile displaying lower cytotoxicity as compared with their counterparts lacking the disulfide linkage, in part due to the intracellular degradation of the disulfide linkage. We have recently developed bioreducible disulfide-based polyethylenimine (SSPEI) for potent in vitro and in vivo delivery of siRNA targeting human telomerase reverse transcriptase (hTERT). It was found that SSPEI-delivered hTERT siRNA induced significant growth inhibition of different human cancer cells in vitro and also tumor growth suppression in vivo. Importantly, the SSPEI, at an appropriate dose, revealed a negligible adverse effect on cellular metabolic activity in vitro and liver and kidney function in vivo.
authors: Tongji University School of Medicine, Tongji University, 200092, P.R. China.
authors: Wei
authors: W
authors: Xia
authors: Chao
authors: C
authors: Lin
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004220:Disulfides / Q000737:chemistry* / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D004220:Disulfides; D011108:Polymers; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; C509186:TERT protein, human; D019098:Telomerase