title: Reiterated Targeting Peptides on the Nanoparticle Surface Significantly Promote Targeted Vascular Endothelial Growth Factor Gene Delivery to Stem Cells.
abstract: Nonviral gene delivery vectors hold great promise for gene therapy due to the safety concerns with viral vectors. However, the application of nonviral vectors is hindered by their low transfection efficiency. Herein, in order to tackle this challenge, we developed a nonviral vector integrating lipids, sleeping beauty transposon system and 8-mer stem cell targeting peptides for safe and efficient gene delivery to hard-to-transfect mesenchymal stem cells (MSCs). The 8-mer MSC-targeting peptides, when synthetically reiterated in three folds and chemically presented on the surface, significantly promoted the resultant lipid-based nanoparticles (LBNs) to deliver VEGF gene into MSCs with a high transfection efficiency (∼52%) and long-lasting gene expression (for longer than 170 h) when compared to nonreiterated peptides. However, the reiterated stem cell targeting peptides do not enable the highly efficient gene transfer to other control cells. This work suggests that the surface presentation of the reiterated stem cell-targeting peptides on the nonviral vectors is a promising method for improving the efficiency of cell-specific nonviral gene transfection in stem cells.
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Institute of Applied Bioresource Research, College of Animal Science, Zhejiang University , Hangzhou, Zhejiang 310058, China.
authors.forename: Mingying
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Mao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival; D004705:Endocytosis; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D051381:Rats; D019076:Transgenes; D019895:Transposases / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D010455:Peptides; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C038089:1,2-distearoylphosphatidylethanolamine; C094877:dioleoyl phosphatidylethanolamine; D019895:Transposases; C494471:sleeping beauty transposase, human; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane