A polymer nanoplatform with high transfection rate for the efficient gene therapy of peripheral arterial diseases

Gene therapy has great potential in the treatment of peripheral arterial diseases (PAD). However, the commercial used carrier for gene therapy, polyethyleneimine (PEI) 25 kDa is not efficient in transfection in vivo and is difficult to degrade. In this work, PEI 1.8 kDa was cross-linked with glutaraldehyde , and glutaraldehyde-PEI (GAPEI) was obtained by a simple wet chemistry synthetic process. The prostacyclin synthase (PTGIS) plasmid was further wrapped by GAPEI to form a polymer with a size of ∼150  nm and a positive potential for transfection. The western blotting experiment showed that the level of PTGIS protein synthesis in cells transfected by GAPEI was 1.48 times higher than that of PEI25kDa. He cytotoxicity test showed that GAPEI had lower cytotoxicity. In vitro and in vivo experiments showed a significant increase in locally secreted prostacyclin (PGI2) after transfection of PTGIS plasmid. The ability of cells to establish tube and chemotaxis to stem cells increased, and these phenotypic changes may be involved in the vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF-β1), and fibroblast growth factor 2 (FGF2) pathways. This work promotes the potential applications of GAPEI-PTGIS nanoparticles for PAD therapy and provides design concepts for the synthesis of therapeutic agents for PAD therapy.