title: Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors.
abstract: The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition-fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS(®) Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored noncytotoxic nano vesicles show significant potential for use in practical gene therapy.
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai, China. liwei.dds@gmail.com
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Huafei
authors.initials: H
authors.lastname: Li
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.forename: Huajing
authors.initials: H
authors.lastname: Wang
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Zengwei
authors.initials: Z
authors.lastname: Ye
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dai
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000235:genetics*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D000180:Acrylic Resins; D053769:Nanocapsules; D011109:Polymethacrylic Acids; C015460:poly(acryloylmorpholine); C068872:polybutyl methacrylate; D004247:DNA