Biomimetic Targeting Nanoplatform for Atherosclerosis Theranostics Via Photoacoustic Diagnosis and “Hand‐In‐Hand” Immunoregulation

Abstract 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 (T reg ) cells. The transforming growth factor beta (TGF‐β) expressed by up‐regulated M2 macrophages also intensifies the T reg 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.