title: Large-pore mesoporous silica nanospheres as vehicles for delivering TRAF3-shRNA plasmids to Kupffer cells.
abstract: The currently available techniques for transferring exogenous genes into macrophages, especially the targeted import of exogenous genes into Kupffer cells (KCs) in vivo, are inefficient and achieve only low targeting. Novel Large-Pore Mesoporous Silica Nanospheres (LPMSNs) may be a promising gene transfection agent for KCs because of their superior biodegradation and hypotoxic characteristics, as well as their ability to retain the biological function of KCs and the high loading-rate of exogenous plasmid. LPMSNs were able to completely adsorb shRNA-TRAF3 (tumor necrosis factor receptor-associated factor-3) plasmid at a mass ratio as low as 30:1, and exhibited a low cytotoxicity for KCs. LPMSNs were detected in KC cytoplasm in vitro, and transmission electron microscopy (TEM) revealed that they were present only in KCs in liver tissue in vivo. The max KC transfection efficiency with LPMSNs was 34.8± 0.07%, as evaluated using flow cytometry, and the protein and mRNA levels of TRAF3 were significantly inhibited (P < 0.05) by shRNA-TRAF3 plasmid transfection after 24 h in vitro and 48 h in vivo. In conclusion, KC targeted transfection was achieved successfully by LPMSNs carrying shRNA-TRAF3 plasmids in vitro and vivo. The protein and mRNA levels of TRAF3 were suppressed significantly. These results suggest that LPMSNs are a promising vehicle for delivering exogenous genes into KCs in vitro and vivo.
authors.affiliation: Department of Hepatobiliary Surgery and Department of Urinary Surgery, The Second Affiliated Hospital of Chongqing Medical University, China. Electronic address: zhangmachine@hotmail.com.
authors.forename: Junyong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, China. Electronic address: guoshipeng2008@126.com.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, China. Electronic address: Sadengren8881@163.com.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, China. Electronic address: niudechao_2002@163.com.
authors.forename: Dechao
authors.initials: D
authors.lastname: Niu
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, China. Electronic address: gjp_cqmu@yeah.net.
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D065966:Absorption, Physicochemical; D002470:Cell Survival / Q000187:drug effects; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058608:Nanopores / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry / Q000648:ultrastructure; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D016062:Porosity; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D012822:Silicon Dioxide / Q000737:chemistry; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics*; D014162:Transfection / Q000379:methods*
chemical_list: D053769:Nanocapsules; D034741:RNA, Small Interfering; D048008:TNF Receptor-Associated Factor 3; D012822:Silicon Dioxide
keywords: DNA transfection; Engineered nanomaterials; Inherent macrophages of liver; TRAF3