Design of a Multifunctional Nanozyme for Resolving the Proinflammatory Plaque Microenvironment and Attenuating Atherosclerosis

Persistent inflammation within atherosclerotic plaquesis a crucialfactor contributing to plaque vulnerability and rupture. It has becomeincreasingly evident that the proinflammatory microenvironment ofthe plaque, characterized by heightened monocyte recruitment, oxidativestress, and impaired clearance of apoptotic cells, plays a significantrole in perpetuating inflammation and impeding its resolution. Consequently,targeting and eliminating these proinflammatory features within theplaque microenvironment have emerged as a promising therapeutic approachto restore inflammation resolution and mitigate the progression ofatherosclerosis. While recent advancements in nanotherapeutics havedemonstrated promising results in targeting individual proinflammatorycharacteristics, the development of an effective therapeutic strategycapable of simultaneously addressing multiple proinflammatory featuresremains a challenge. In this study, we developed a multifunctionalnanozyme based on Prussian blue, termed PBNZ@PP-Man, to simultaneouslytarget and eliminate various proinflammatory factors within the plaquemicroenvironment. Through systematic investigations, we have elucidatedthe antiatherosclerotic mechanisms of PBNZ@PP-Man. Our results demonstratethat PBNZ@PP-Man possesses the ability to accumulate within atheroscleroticplaques and effectively eliminate multiple proinflammatory factors,leading to inflammation resolution. Specifically, PBNZ@PP-Man suppressesmonocyte recruitment, scavenges reactive oxygen species, and enhancesefferocytosis. Notably, PBNZ@PP-Man exhibits a much stronger efficacyto resolve the proinflammatory plaque microenvironment and attenuateatherosclerosis in comparison to the approach that merely eliminatesone single risky factor in the plaque. It significantly enhances theinflammation resolution capabilities of macrophages and attenuatesatherosclerosis. These results collectively underscore the importanceof modulating the proinflammatory plaque microenvironment as a complementarystrategy for resolving inflammation in atherosclerosis.