title: Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment.
abstract: A novel pH-responsive gene delivery system for tumor acidity-targeted pDNA delivery is prepared by introducing a rapid charge-conversional zwitterionic copolymer to the positive surface of PEI/pDNA complexes through electrostatic interaction. The shielding system (OEAL) consists of oligoethylenimine (OEI), poly(l-aspartate) (PBLA), and poly(l-lysine) (PLL). The charge-conversional behavior of the OEAL/PEI/DNA ternary complex is evaluated by zeta potential assay. The surface charges of the complexes can change from negative to positive in the pH range of 7.4-6.8. Under a simulative in vivo environment, OEAL/PEI/DNA exhibits promotion of cellular uptake by tumor cells and enhanced gene transfection efficiency because of its good charge-conversional properties. Antitumor experiments further show that the pH-responsive charge-conversional system can mediate a therapeutic gene that can induce tumor apoptosis (pKH3-rev-casp-3) to achieve effective tumor inhibition. Accordingly, OEAL can be regarded as a promising tumor microenvironment-sensitive gene delivery shielding system for antitumor therapy.
  
  
  CONCLUSIONS
  This manuscript focused on the novel pH-responsive gene delivery system for tumor acidity-targeted pDNA delivery. The novel system is prepared by introducing a rapid charge-conversional zwitterionic copolymer, consisting of oligoethylenimine, poly(l-aspartate) and poly(l-lysine), to the positive surface of PEI/pDNA complexes. The surface charges of the complexes can change from negative to positive from pH 7.4 to 6.8. OEAL/PEI/DNA shows promoting cellular uptake by tumor cells and enhanced gene transfection efficiency. The antitumor experiments further show that the pH responsive charge conversional system can mediate pKH3-rev-casp-3 to achieve effective tumor inhibition. Accordingly, OEAL can be regarded as a promising tumor microenvironment sensitive gene delivery shielding system for antitumor therapy.
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors: Jie
authors: J
authors: Chen
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Xiamen Institute of Measurement and Testing, Xiamen 361000, China.
authors: Xuan
authors: X
authors: Dong
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
authors: Tianshi
authors: T
authors: Feng
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors: Lin
authors: L
authors: Lin
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors: Zhaopei
authors: Z
authors: Guo
authors: School of Chemistry and Chemical Engineering, Lingnan Normal University, 29 Cunjin Road, Zhanjiang, Guangdong 524048, China.
authors: Jialiang
authors: J
authors: Xia
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: thy@ciac.ac.cn.
authors: Huayu
authors: H
authors: Tian
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: xschen@ciac.ac.cn.
authors: Xuesi
authors: X
authors: Chen
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000235:genetics* / Q000628:therapy*; D011108:Polymers / Q000737:chemistry; D055672:Static Electricity; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D007477:Ions; D053769:Nanocapsules; D011108:Polymers; D004247:DNA
keywords: Cell apoptosis; Charge conversion; Rev-caspase-3; Tumor therapy; pH-responsive