Biomimetic Targeting Nanoplatform for Atherosclerosis Theranostics Via Photoacoustic Diagnosis and "Hand-In-Hand" Immunoregulation

Atherosclerosis can cause severe cardiovascular disease, which is usually diagnosed in late stages with life-threatening complications. The lack of obvious symptoms limits its early diagnosis and timely treatment. In this work, a theranostic nanoplatform PGA@PMP is constructed for targeting photoacoustic diagnosis and a "hand-in-hand" immunoregulation of early-stage atherosclerosis. Coated with biomimetic platelet membrane, PGA@PMP can actively target to the pathological endothelium and respond to the reactive oxygen species (ROS) in lesions for further disassembly and releasing photoacoustic probe along with immune-regulate complex GWAS. The photoacoustic probe performs a noninvasive imaging with distinct recognition of plaques. In company, triggered by local cathepsin B, GWAS can be degraded for respective regulation on inducing M2 macrophages and stimulating regulatory T (Treg) cells. The transforming growth factor beta (TGF-beta) expressed by up-regulated M2 macrophages also intensifies the Treg cell differentiation, which synergistically inhibits the foam cell formation and rebuilds a well-balanced immune microenvironment. The in vivo evaluations suggest that the "hand-in-hand" strategy on regulating macrophages polarization and T cell differentiation indicates the restraint on atherosclerotic progression and the reversal of formed lesions even under high-fat diet. Together, PGA@PMP provides an integrated solution for targeting theranostics of early-stage atherosclerosis and delivers an exciting outcome of reversing the formed lesions. A theranostic nanoplatform PGA@PMP is constructed with atherosclerosis-targeting accumulation and ROS/CTSB dual-responsiveness, which indicates a plaque-specific photoacoustic diagnosis and a hand-in-hand immunoregulation through inducing M2 macrophages and stimulating Treg cells with cell communication based on TGF-beta. PGA@PMP provides a candidate for the diagnosis of early-stage plaques, the inhibition of atherosclerosis progression and the reversal of formed lesions even under high-fat diet.image