title: Amphiphilic core-shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells.
abstract: Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core-shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@ PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited (P<0.05) both in vitro and in vivo. These results demonstrate that the PEI@PMMA NPs with a unique amphiphilic core-shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs.
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Zuojin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People's Republic of China; Lab of Low-Dimensional Materials Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Dechao
authors.initials: D
authors.lastname: Niu
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Junyong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D019904:Polymethyl Methacrylate / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D013501:Surface-Active Agents; D011094:Polyethyleneimine; D019904:Polymethyl Methacrylate
keywords: Kupffer cells; amphiphilic core-shell nanoparticles; branched polyethyleneimine; gene delivery