The development of nanomedicines provides new opportunities for the treatment of atherosclerosis (AS) due to their great advantages such as the improved drug solubility, enhanced bioavailability and reduced side effects. Despite these advantages, nanomedicines are still facing some challenges. The problems remain in the short circulation life, lack of specific targeting and poor drug release controllability. In order to overcome the shortages of conventional nanomedicines, the combination of biomimetic strategy with smart nanoagents has been proposed. In light with the high reactive oxygen species (ROS) level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS, we fabricated ROS-responsive biomimetic nanoparticles (NPs), which camouflaged macrophage membrane (MM) on ROS-responsive NPs loaded with rapamycin (RNPs) for potential application in AS therapy. The resulting ROS-responsive biomimetic NPs (MM/RNPs) exhibited favorable hydrodynamic size with negative surface charge, retained the functional proteins from MM, and showed ROS-responsive drug release. Because of the biomimetic camouflaging on surface, MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells. Meanwhile, MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro. Furthermore, the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation. Consequently, these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.

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ROS响应性仿生纳米粒子在靶向抗动脉粥样硬化中的潜在应用

纳米药物的发展为动脉粥样硬化（AS）的治疗提供了新的机遇，因为它们具有改善药物溶解度、提高生物利用度和减少副作用等巨大优势。尽管有这些优势，但纳米药物仍面临一些挑战。存在循环寿命短、缺乏特异性靶向、药物释放可控性差等问题。为了克服传统纳米药物的不足，有人提出将仿生策略与智能纳米药物相结合。鉴于 AS 微环境中的高活性氧 (ROS) 水平以及巨噬细胞在 AS 的发病机制中起关键作用的事实，我们制造了 ROS 响应性仿生纳米粒子 (NPs)，它伪装了负载雷帕霉素（RNP）的ROS反应性NP上的巨噬细胞膜（MM），用于AS治疗。由此产生的 ROS 响应性仿生 NPs (MM/RNPs) 表现出良好的流体动力学尺寸和负表面电荷，保留了 MM 中的功能蛋白，并显示出 ROS 响应性药物释放。由于表面的仿生伪装，MM / RNPs可以有效地逃避巨噬细胞的摄取并靶向炎症内皮细胞。同时，MM/RNPs在体外可以抑制巨噬细胞和平滑肌细胞的增殖。此外，发现 MM 包被的 NP 在细胞毒性测定和体内毒性评估中均无毒。所以，