Combining oxygen delivery and generation for targeted atherosclerosis therapy.

Hypoxia plays an important role in the progression of atherosclerosis. However, ameliorating hypoxia at atherosclerotic lesions remains a great challenge. To achieve targeted oxygen delivery to atherosclerotic plaques, Lipid 5-doped, platelet membrane-encapsulated magnetic mesoporous organosilicon nanoparticles loaded with perfluoro-15-crown ether (PFCE) (FMMON@PL) were prepared. PFCE worked as an oxygen carrier, while iron oxide nanoparticles (IONPs) acted as nanozymes with catalase-like activity to facilitate oxygen generation. To enhance plaque targeting, platelet membranes were coated onto mesoporous organosilicon nanoparticles containing PFCE and IONPs. Lipid 5 containing a tertiary amine was doped into the platelet membranes for lysosomal escape. Our results demonstrated that FMMON@PL specifically targeted macrophages in atherosclerotic plaques. FMMON@PL significantly reduced HIF-1α expression, ameliorated oxidative stress, inhibited foam cell formation, and reduced M1 macrophage polarization. In conclusion, FMMON@PL successfully achieved oxygen delivery within plaques and inhibited plaque progression, demonstrating the feasibility of hypoxia alleviation for the treatment of atherosclerosis.