title: Tumor Acidity-Induced Sheddable Polyethylenimine-Poly(trimethylene carbonate)/DNA/Polyethylene Glycol-2,3-Dimethylmaleicanhydride Ternary Complex for Efficient and Safe Gene Delivery.
abstract: Amphiphilic PEI derivatives/DNA complexes are widely used for DNA delivery, but they are unstable in vivo and have cytotoxicity due to the excess cationic charge. PEGylation of cationic complexes can improve sterical stability and biocompatibility. However, PEGylation significantly inhibits cellular uptake and endosomal escape. In this work, sheddable ternary complexes were developed by coating a tumor acidity-sensitive β-carboxylic amide functionalized PEG layer on the binary complexes of amphiphilic cationic polyethylenimine-poly(trimethylene carbonate) nanoparticles/DNA (PEI-PTMC/DNA). Such sheddable ternary complexes markedly reduced their nonspecific interactions with serum protein in the bloodstream and obtained minimal cytotoxicity due to the protection of the PEG shell. At the tumor site, the PEG layer was deshielded by responding to the tumor acidic microenvironment and the positively charged complexes re-exposed that had higher affinity with negatively charged cell membranes. Meanwhile the positively charged complexes facilitated endosomal escape. Accordingly, this delivery system improved the biocompatibility of gene-loaded complexes and enhanced the gene transfection efficiency. Such PEGylated complexes with the ability to deshield the PEG layer at the target tissues hold great promise for efficient and safe gene delivery in vivo.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Caiyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Leihou
authors.initials: L
authors.lastname: Shao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Lu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Deng
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
mesh_terms: D004247:DNA / Q000737:chemistry / Q000494:pharmacology; D004146:Dioxanes / Q000737:chemistry / Q000494:pharmacology; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008299:Maleic Anhydrides / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004146:Dioxanes; D008299:Maleic Anhydrides; D011108:Polymers; C059299:polytrimethylene carbonate; D011092:Polyethylene Glycols; C007474:2,3-dimethylmaleic anhydride; D011094:Polyethyleneimine; D004247:DNA; C000595209:polyethylene glycol 1000
keywords: PEGylation; gene delivery; polyethylenimine-poly(trimethylene carbonate); sheddable; tumor acidity