Therapeutic Effects of Nanoparticles Loaded with Combined Sense and Anti-Sense of EpoR Plasmids to Enhance Angiogenesis

We employed nanoparticle (NP) platforms to enhance the delivery of both erythropoietin receptor (EpoR) plasmids (pEpoR) and the antisense of pEpoR (pRopE) to induce angiogenesis in ischemic tissues of peripheral arterial disease (PAD). Poly (lactic-co-glycolic acid) (PLGA) NPs loaded with these plasmids were successfully fabricated and characterized. In migration assays, pEpoR/pRopE NPs exhibited a synergistic effect, significantly outperforming pEpoR NPs alone (by 3.7-fold) and pRopE NPs alone (by 2.3-fold). Furthermore, the dual-plasmid NPs significantly enhanced cell survival and facilitated tube formation compared to the VEGF-treated group. In a PAD animal model, pEpoR/pRopE NPs improved blood perfusion in ischemic limbs by 3.8-fold and increased capillary densities in the gastrocnemius muscle by 4.7-fold compared to the VEGF group. In conclusion, pEpoR/pRopE NPs successfully transfected ischemic cells, enhancing both blood perfusion and capillary densities in ischemic tissues, highlighting their therapeutic potential for PAD treatment.