title: Sandwich-type Au-PEI/DNA/PEI-Dexa nanocomplex for nucleus-targeted gene delivery in vitro and in vivo.
abstract: Many synthetic Au-based cationic nanoparticles (AuNPs) for nonviral gene delivery show high efficiency in vitro, but their excessive charge density, harsh reducing conditions, and nontarget delivery prevent their application in vivo. Herein, we constructed a sandwich-type layered polyethylenimine (PEI)-coated gold nanocomposite outerlaid with a nucleus-targeted Dexamethasone (Dexa), namely, Au-PEI/DNA/PEI-Dexa nanocomplex, for DNA delivery system using a low molecular weight PEI as a mild reducing agent. The nucleus-targeting Au-PEI/DNA/PEI-Dexa nanocomplex with low positive charge and low cytotoxicity condensed DNA and protected from enzymatic degradation. In vitro transfection studies demonstrated that Au-PEI/DNA/PEI-Dexa nanocomplex exhibited much more efficient nucleus transfection than Au-PEI/DNA/PEI without nucleus-targeted residues and commercially available PEI 25 kDa due to the Dexa targeting of the nucleus. Furthermore, the nanocomplex markedly transfected pTRAIL (TRAIL = tumor-necrosis-factor-related apoptosis-inducing ligand) to tumors in vivo and subsequently inhibited the tumor growth with minimal side effects. These findings suggest that nucleus-targeting Au-PEI/DNA/PEI-Dexa ternary complexes have promising potential in gene delivery.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering & Environmental Technology, Lanzhou University , Lanzhou 730000, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Lifen
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuling
authors.initials: Y
authors.lastname: He
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D003907:Dexamethasone / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D006046:Gold; D003907:Dexamethasone; D011094:Polyethyleneimine; D004247:DNA