Angiogenesis-promoting properties of phosphorylcholine mimetic nanoparticles.

Therapeutic angiogenesis aims to re-establish the blood supply to ischemic tissues. We developed a novel strategy in which nanoparticles (NPs) made from polymers of an artificial methacrylated phosphorylcholine (polyMPC) were used directly to stimulate angiogenesis. PolyMPC NPs under 150 nm were internalized by cultured human umbilical vein endothelial cells (HUVECs) in vitro, stimulating their proliferation and angiogenic responses. In vivo, the subcutaneous implantation of polyMPC NPs delivered within Matrigel plugs in mice produced a significant pro-angiogenic response. PolyMPC NPs were also shown to induce expansion of human cord blood and bone marrow endothelial progenitor cells. Mechanistically, internalization of polyMPC NPs by HUVECs induced the recruitment of protein kinase C (PKC) to the plasma membrane leading to its activation. RNA sequencing revealed that polyMPC NPs upregulated pro-angiogenic growth factors in HUVECs, including VEGF and FGF2. Delivered polyMPC NPs could be retained in tissues for extended periods, stimulating endogenous production of pro-angiogenic growth factors for therapeutic effects. Overall, we demonstrated that angiogenesis therapy based on polyMPC NPs could be a novel alternative, cost-effective method to treat ischemic vascular pathologies.