title: Suppression of VEGF by reversible-PEGylated histidylated polylysine in cancer therapy.
abstract: A reversible-PEGylated polylysine is designed and developed for efficient delivery of siRNA. In this unique structure, the ε-amino groups of disulfide linked poly(ethylene glycol) (PEG) and polylysine (mPEG-SS-PLL) are partially replaced by histidine groups, in order to develop the histidylated reversible-PEGylated polylysine (mPEG-SS-PLH), for enhanced endosome escape ability. The transfection efficacy of mPEG-SS-PLH is found to closely correlate with histidine substitution. Its maximum transfection efficiencies are determined, respectively, to be 75%, 42%, and 24%, against 293T, MCF-7, and PC-3 cells. These data indicate that the transfection efficiencies can equal or even outweigh PEI-25k in the corresponding cells (80%, 38.5%, and 20%). The in vivo circulation and biodistribution of the polyplexes are monitored by fluorescent imaging. The in vivo gene transfection is carried out by intravenous injection of pEGFP to BALB/c mice using the xenograft models. The in vivo experimental results show effective inhibition of tumor growth by mPEG-SS-PLH/siRNA-VEGF, indicating its high potential for clinical applications.
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Tongji University, Shanghai, 200120, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Cai
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Haiqing
authors.initials: H
authors.lastname: Dong
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Li
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Su
authors.forename: Donglu
authors.initials: D
authors.lastname: Shi
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry* / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D014018:Tissue Distribution; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D011107:Polylysine; D011092:Polyethylene Glycols; D006639:Histidine
keywords: PEGylation; VEGF; endosomal escape; gene therapy; histidylation