A drug delivery system of HIF-1α siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1α siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV). Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection. Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis. A HIF-1α siRNA-loaded PLGA@lipid hybrid nanoparticles system was designed. An MSC-mediated biodegradable hybrid nanoparticle system for targeted delivery of HIF-1α siRNA was developed. The MSC-mediated homing enabled targeted ocular angiogenesis. MSCs can be potentially exploited as an ideal drug delivery system, a so-called Trojan horse strategy. Systemic administration of MSCs loaded with nanoparticles inhibited pathological angiogenesis. Integration of advanced nanomaterials with cell-based platforms can amplify the overall therapeutic impact. MSCs can be safely delivered without triggering a major immune reaction. The ability of MSCs to specifically migrate to CNV without accrual in other organs.