Sonodynamic therapy (SDT) and photothermal therapy (PTT) are two effective strategies for the treatment of atherosclerotic plaques. However, the low yield of reactive oxygen species (ROS) of conventional organic sonosensitizers and the low biosafety of hyperthermia limit the therapeutic efficacy of SDT and PTT. Herein, we report copper sulfide/titanium oxide heterostructure nanosheets modified with hyaluronic acid (HA) and PEG (HA-HNSs) for low-intensity sonodynamic and mild-photothermal synergistic therapy for early atherosclerotic plaques. CuS/TiO₂ 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.

中文翻译：

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使用 CuS/TiO2 异质结构纳米片预防动脉粥样硬化斑块进展的巨噬细胞靶向声动力/光热协同疗法

声动力疗法（SDT）和光热疗法（PTT）是治疗动脉粥样硬化斑块的两种有效策略。然而，常规有机声敏剂的活性氧（ROS）产率低和热疗的生物安全性低限制了SDT和PTT的治疗效果。在此，我们报告了用透明质酸 (HA) 和 PEG (HA-HNSs) 修饰的硫化铜/氧化钛异质结构纳米片，用于早期动脉粥样硬化斑块的低强度声动力学和轻度光热协同治疗。硫化铜/_二氧化钛异质结构纳米片 (HNSs) 显示出高电子空穴分离效率和卓越的声动力学性能，因为它具有高表面能晶面和窄带。此外，HNSs 在 NIR-II 区域表现出强烈的吸光度，这赋予纳米片优异的光热性能。通过对 HA 的进一步修饰，HA-HNSs 可以通过 CD44-HA 相互作用选择性地靶向斑块内促炎巨噬细胞。由于 SDT 降低了热休克蛋白 90 的表达，而 PTT 促进了声催化过程，因此基于 HA-HNSs 的 SDT 和 PTT 的组合可以协同诱导促炎性巨噬细胞凋亡。更重要的是，协同疗法通过去除病变巨噬细胞和减轻炎症来防止早期动脉粥样硬化斑块的进展。