title: Bioinspired phosphorylcholine-modified polyplexes as an effective strategy for selective uptake and transfection of cancer cells.
abstract: We demonstrated here that the phosphorylcholine-modified polyplexes can be explored as effective gene vector for selective uptake and high transfection of cancer cells. 12-acryloyloxy dodecyl phosphorylcholine modified polyethyleneimine (PEI-ADPC) with grafting level about 13%, 8.3% and 4.5% was successfully synthesized. Gel retardation assay indicated that ADPC modification did not affect the DNA condensation ability. The PEI-ADPC13%/DNA and PEI-ADPC8.3%/DNA polyplexes were under 100nm with a beneficial neutral surface at N/P ratio of 30. Sufficient ADPC shell endowed the polyplexes with high colloidal stability and low cytotoxicity. Compared to PEGylated polyplexes, it was interesting to find out that the PEI-ADPC/DNA polyplexes were selectively uptaked by liver cancer HepG2 cells. At the presence of chloroquine to exclude the limitation of lysosome escape, the ADPC-modified polyplexes showed more effective gene transfection in cancer cells than in normal cells because of the selective cell uptake. In conclusion, the convenient PC-modification modality was found to have both the function of biostability in the physiological environment and targetability toward cancer cells uniquely, which might have great potential use in cancer gene therapy.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China. Electronic address: yx_wang@zju.edu.cn.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China. Electronic address: jijian@zju.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D010767:Phosphorylcholine / Q000138:chemical synthesis* / Q000737:chemistry; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D012492:Salts; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D012492:Salts; D010767:Phosphorylcholine; D002738:Chloroquine; D011094:Polyethyleneimine; D004247:DNA
keywords: Non-virus gene vector; Phosphorylcholine; Polyethyleneimine; Selective uptake