Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of β-cyclodextrin (β-CD), a nanoplatform encapsulating the unstable drug (−)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from β-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE^–/– mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.

中文翻译：

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β-环糊精和透明质酸修饰的靶向纳米递送系统预防动脉粥样硬化


天然产物因其低毒、高活性而在临床治疗中得到广泛认可。值得关注的是，将生物聚合物改性为纳米结构，赋予天然活性成分额外的靶向作用。在这项研究中，基于β-环糊精（β-CD）的多功能修饰，设计了一种封装不稳定药物（−）-表儿茶素没食子酸酯（ECG）的纳米平台，用于递送至动脉粥样硬化斑块。分别通过缩醛化和酯交换反应由 β-CD 和透明质酸合成响应低 pH 环境的缩醛化环糊精 (PH-CD) 和靶向巨噬细胞膜上 CD44 受体的透明质酸环糊精。采用溶剂蒸发法制备负载心电图的双载体纳米颗粒（Double-NPs）。 Double-NPs有效清除活性氧，促进巨噬细胞迁移，抑制巨噬细胞凋亡，抑制血管平滑肌细胞的异常增殖和迁移。此外，在高脂饮食喂养的 ApoE ^–/– 小鼠中，Double-NPs 在动脉粥样硬化斑块中积极积累，导致斑块面积减少、炎症浸润和斑块不稳定。我们的研究结果表明，新开发的心电图纳米制剂代表了治疗动脉粥样硬化等疾病的有效且安全的纳米疗法。