title: Self-assembled human serum albumin-coated complexes for gene delivery with improved transfection.
abstract: The efficiency and safety of gene delivery vectors were important factors for gene therapy. To enhance gene transfection efficiency and to incorporate biocompatible components to the polyamidoamine (PAMAM) dendrimer mediated gene delivery systems, human serum albumin (HSA) was introduced to dendriplexes of PAMAM dendrimer and DNA via electrostatic interactions to form self-assembled PAMAM/DNA/HSA complexes (HSA-dendriplexes). The self-assembled complexes were characterized by gel retardation assay and particle size and zeta potential analysis. Meanwhile, the toxicity of HSA-dendriplexes was evaluated by the MTT assay and haemolysis test, which indicated that the complexes exhibited decreased cytotoxicity with the incorporation of HSA. As compared to dendriplexes, the ternary HSA-dendriplexes increased the enhanced green fluorescent protein gene (EGFP) expression in vitro by 1.7-fold. In addition, HSA-dendriplexes showed a significantly higher luciferase gene expression than dendriplexes or naked DNA in the liver, kidney, lungs and spleen of mice. Our results demonstrated that HSA-dendriplexes increases PAMAM mediated gene transfection efficiency and decreases the cytotoxicity and haemolysis, which made the ternary complexes a promising targeting gene delivery system.
authors.affiliation: Laboratory of Pharmaceutics, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Hao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yin
authors.forename: Mingshu
authors.initials: M
authors.lastname: Ma
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000327:Adsorption; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry; D004563:Electrochemistry; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008027:Light; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D012542:Scattering, Radiation; D012709:Serum Albumin / Q000737:chemistry*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection / Q000379:methods*
chemical_list: D004396:Coloring Agents; D050091:Dendrimers; C104700:PAMAM Starburst; D012709:Serum Albumin; D013778:Tetrazolium Salts; D013844:Thiazoles; D049452:Green Fluorescent Proteins; D004247:DNA; C022616:thiazolyl blue