title: An MRI-visible non-viral vector bearing GD2 single chain antibody for targeted gene delivery to human bone marrow mesenchymal stem cells.
abstract: The neural ganglioside GD2 has recently been reported to be a novel surface marker that is only expressed on human bone marrow mesenchymal stem cells within normal marrow. In this study, an MRI-visible, targeted, non-viral vector for effective gene delivery to human bone marrow mesenchymal stem cells was first synthesized by attaching a targeting ligand, the GD2 single chain antibody (scAbGD2), to the distal ends of PEG-g-PEI-SPION. The targeted vector was then used to condense plasmid DNA to form nanoparticles showing stable small size, low cytotoxicity, and good biocompatibility. Based on a reporter gene assay, the transfection efficiency of targeting complex reached the highest value at 59.6% ± 4.5% in human bone marrow mesenchymal stem cells, which was higher than those obtained using nontargeting complex and lipofectamine/pDNA (17.7% ± 2.9% and 34.9% ± 3.6%, respectively) (P<0.01). Consequently, compared with the nontargeting group, more in vivo gene expression was observed in the fibrotic rat livers of the targeting group. Furthermore, the targeting capacity of scAbGD2-PEG-g-PEI-SPION was successfully verified in vitro by confocal laser scanning microscopy, Prussian blue staining, and magnetic resonance imaging. Our results indicate that scAbGD2-PEG-g-PEI-SPION is a promising MRI-visible non-viral vector for targeted gene delivery to human bone marrow mesenchymal stem cells.
authors.affiliation: Molecular Imaging Lab, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China ; Interventional Radiology Institute of Sun Yat-sen University, Guangzhou, China ; Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Pang
authors.forename: Chun
authors.initials: C
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Faming
authors.initials: F
authors.lastname: Gong
authors.forename: Kangshun
authors.initials: K
authors.lastname: Zhu
authors.forename: Zaibo
authors.initials: Z
authors.lastname: Jiang
authors.forename: Shouhai
authors.initials: S
authors.lastname: Guan
authors.forename: Hong
authors.initials: H
authors.lastname: Shan
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
mesh_terms: D000328:Adult; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005732:Gangliosides / Q000276:immunology; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014162:Transfection / Q000379:methods* / Q000592:standards; D014183:Transplantation, Heterologous; D055815:Young Adult
chemical_list: D005732:Gangliosides; D058185:Magnetite Nanoparticles; D057127:Single-Chain Antibodies; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; C019403:ganglioside, GD2; D011094:Polyethyleneimine