The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis. BPNSs can effectively scavenge a broad spectrum of ROS and suppress atherosclerosis-associated pro-inflammatory cytokine production in lesional macrophages. We also demonstrate ROS-responsive, targeted-peptide-modified BPNS-based carriers for the delivery of resolvin D1 (an inflammation-resolving lipid mediator) to lesional macrophages, which further boosts the anti-atherosclerotic efficacy. The targeted nanotherapeutics not only reduce plaque areas but also substantially improve plaque stability in high-fat-diet-fed apolipoprotein E-deficient mice. This study presents a therapeutic strategy against atherosclerosis, and highlights the potential of BPNS-based therapeutics to treat other inflammatory diseases.

动脉粥样硬化中斑块的积聚会导致心血管事件，而慢性未解决的炎症和活性氧（ROS）的过量产生是斑块进展的主要驱动因素。可以解决炎症和清除ROS的纳米疗法具有治疗动脉粥样硬化的潜力。在这里，我们展示了黑磷纳米片（BPNS）作为治疗动脉粥样硬化的治疗剂的潜力。 BPNS 可以有效地清除广谱 ROS，并抑制病变巨噬细胞中动脉粥样硬化相关的促炎细胞因子的产生。我们还展示了 ROS 响应、靶向肽修饰的基于 BPNS 的载体，用于将 resolvin D1（一种炎症缓解脂质介质）递送至病变巨噬细胞，从而进一步增强抗动脉粥样硬化功效。靶向纳米疗法不仅可以减少斑块面积，还可以显着改善高脂肪饮食喂养的载脂蛋白 E 缺陷小鼠的斑块稳定性。这项研究提出了一种针对动脉粥样硬化的治疗策略，并强调了基于 BPNS 的疗法治疗其他炎症性疾病的潜力。