pVEGF-loaded lipopolysaccharide-amine nanopolymersomes for therapeutic angiogenesis

摘要

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 lipopolysaccharideamine 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 pVEGFloaded 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 ℃ 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) ~35fold greater than that for the untreated group. VNPs induce significant and dosedependent angiogenesis in zebrafish without causing death, deformity or delay in growth and development, and the induced maximal vessel area of subintestinal vessel plexus is 2.5fold higher than that for the untreated group. Our study suggests that VNP has high potential in therapeutic angiogenesis.