Abstract：
Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial reactive oxygen species (ROS) scavenging, hydrogen anti-inflammation, and autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitro and in vivo results confirmed the synergy among the antioxidation, anti-inflammatory, and autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.
摘要：
动脉粥样硬化,由动脉壁的慢性炎症驱动，是几种严重心血管疾病的基础。然而,目前可用的基于抗炎的动脉粥样硬化治疗策略存在疗效受损和不良治疗结果.在这里，设计并设计了一种独特的四足针状PdH纳米酶，用于通过组合活性氧（ROS）清除来有效治疗动脉粥样硬化，氢抗炎症，和自噬激活。在加载到巨噬细胞并靶向递送到动脉斑块后，这些多功能纳米酶有效地降低了ROS水平，并显着抑制了炎症相关的病理过程，发挥独特的抗氧化和抗炎性能，缓解动脉粥样硬化的发展。尤其重要的是,PdH纳米酶的特定尖峰形态进一步触发了巨噬细胞的强烈自噬反应，协同维持细胞稳态和缓解动脉粥样硬化发展。体外和体内结果都证实了抗氧化之间的协同作用，抗炎,和自噬激活，这表明，具有内在多种治疗功能和拓扑诱导的生物学效应的纳米药物的组合工程对于实现动脉粥样硬化管理和治疗的高治疗性能和理想的治疗结果是非常优选和有效的。
