A New Type Gene Delivery System – Gene Nanoparticles

A reporter gene pEGFP and a therapeutic antisense monocyte hemotactic protein-1 (MCP-1) gene were encapsulated into poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using an emulsification / solvent evaporation technique. The gene-NPs were around 300 nm in diameter with very narrow size distribution. The encapsulation efficiency of DNA was significantly improved when poly (lysine) was used in cooperation with DNA. The NPs demonstrated a steady in vitro release of DNA with more that 95% of total enclosed DNA released within 14 days. In cell culture, pEGFP -loaded NPs were able to express in smooth muscle cells at a level same as that of Lipofectin induced plasmid. To observe the effects of antisense MCP-1 NPs on the inhibition of restenosis, balloon catheter-induced injury was used to establish an intimal hyperplasia model of rabbit carotid artery. Antisense MCP-1 expression was confirmed in the artery tissue with local delivery of the therapeutic NP into the injured artery. Intima/media ratio of arteries treated with the antisense NPs was reduced by 43% compared with control group. In conclusion, NP could be an effective gene carrier for intravascular site-specific gene therapy.