Pretreatment of macrophage-membrane-coated nanoparticles for therapeutical targeting of P. gingivalis-accelerated atherosclerosis

Atherosclerosis (AS) as a chronically inflammatory disease is the mainly cause of mortality worldwide. Porphyromonas gingivalis (P. gingivalis, Pg), one primary pathogen in periodontitis (PD), has been reported to promote the progression of atherosclerosis via inducing infectiously triggered immune response, thus accelerating atheromatous plaque formation. However, limited therapeutic potency has been achieved using traditional drug treatment due to the existence of Pg and low concentration of drug reached in AS, reminding us to develop a new drug delivery strategy. In this study, to simultaneously realize the pathogen elimination and inflammation resolution in Pg-infected region, the PLGA-simvastatin-chitosan-metronidazole nanoparticles (STNPs) were coated with Pg-treated macrophage membranes (MM/STNPs). These nanoparticles obviously eliminated the amount of Pg and effectively switched the activation of macrophages from an inflammatory M1-like state to a more immunosuppressive M2-like phenotype. Using Pg-treated macrophage membrane (MM), the MM/STNPs were efficiently targeted in both atheromatous plaque and periodontal tissue in vivo. Importantly, MM/STNPs injection simultaneously diminished the atheromatous plaque formation in AS and rejuvenated the alveolar bone loss in PD. Based on this specific Pg-targeted delivery, the biomimetic nanoparticles provide a new approach for the targeting strategy in the treatment of Pg-accelerated AS.