title: pVEGF-loaded lipopolysaccharide-amine nanopolymersomes for therapeutic angiogenesis.
abstract: Therapeutic angiogenesis via gene delivery is promising for tissue survival and regeneration after injury or ischemia. A stable, safe and efficient gene vector is essential for successful angiogenesis. We have demonstrated that our newly developed lipopolysaccharide-amine nanopolymersomes (LNPs) have higher than 95% transfection efficiency when delivering pEGFP into mesenchymal stem cells (MSCs). To explore their clinical potential in therapeutic angiogenesis, in this study, we studied their toxicity, storage stability, protection ability to genes and efficacy to deliver therapeutic genes of pVEGF in MSCs and zebrafish. The results show that LNPs can condense pVEGF to form pVEGF-loaded nanopolymersomes (VNPs), and protect pVEGF against DNase digestion in 6 h. Both LNPs and VNPs have low toxicity to MSCs, erythrocytes and zebrafish embryos. LNPs are stable at 4 °C for at least two years with unchanged size and transfection efficiency. MSCs transfected by VNPs continuously synthesize VEGF for at least four days under control, with a peak (21.25 ng ml(-1)) ∼35-fold greater than that for the untreated group. VNPs induce significant and dose-dependent angiogenesis in zebrafish without causing death, deformity or delay in growth and development, and the induced maximal vessel area of subintestinal vessel plexus is 2.5-fold higher than that for the untreated group. Our study suggests that VNP has high potential in therapeutic angiogenesis.
authors.affiliation: Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology,Sun Yat-sen University, Guangdong 510600, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Teng
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Qinmei
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003851:Deoxyribonucleases / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D018919:Neovascularization, Physiologic; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*; D015027:Zebrafish
chemical_list: D008070:Lipopolysaccharides; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D003851:Deoxyribonucleases