Macrophage-Targeted Sonodynamic/Photothermal Synergistic Therapy for Preventing Atherosclerotic Plaque Progression Using CuS/TiO2 Heterostructured Nanosheets

heterostructure nanosheets (HNSs) show high electron-hole separation efficiency and superior sonodynamic performance, because it has high surface energy crystal facets as well as a narrow band. Moreover, HNSs exhibit intense absorbance in the NIR-II region, which endows the nanosheets with excellent photothermal performance. With a further modification of HA, HA-HNSs can selectively target intraplaque proinflammatory macrophages through CD44-HA interaction. Because SDT reduces the expression of heat shock protein 90 and PTT facilitates the sonocatalytic process, the combination of SDT and PTT based on HA-HNSs could synergistically induce proinflammatory macrophage apoptosis. More importantly, the synergistic therapy prevents the progression of early atherosclerotic plaque by removing lesional macrophages and mitigating inflammation. Taken together, this work provides a macrophage-targeting sonodynamic/photothermal synergistic therapy, which is an effective translational clinical intervention for early atherosclerotic plaques.