Li Zhipeng, Wang Wenyu, Zhu Liping, Wang Zhiqiang, Liu Chaolong, Sun Yong, Wu Jingliang, Wang Qing
School of Medicine, Weifang University of Science and Technology, Weifang 262700, China.
Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
ACS Appl Mater Interfaces. 2025 May 21;17(20):29210-29223. doi: 10.1021/acsami.5c03170. Epub 2025 May 7.
Diabetic retinopathy (DR), as the most common microvascular complication of diabetes, seriously threatens the vision of diabetic patients. As the resident phagocytes of the retina, microglia participate in inflammation, neovascularization, and neurodegeneration of DR. Herein, apoptotic retinal cell membrane-coated, rapamycin-loaded mesoporous Prussian blue NPs as immunomodulators for ameliorating DR by modulating microglial polarization are reported. The apoM@mPB@Ra NPs exhibited favorable stability and biocompatibility and achieved active targeted delivery due to the specific recognition between "eat me" signal expressed on apoptotic membrane and microglia. In an LPS-induced cellular inflammation model, apoM@mPB@Ra NPs effectively promoted microglial polarization toward the anti-inflammatory phenotype (M2) by scavenging intracellular reactive oxygen species (ROS) combined with affecting the mTOR signaling pathway, leading to downregulation of pro-inflammatory cytokines IL-6 and TNF-α. Meanwhile, owing to the multienzyme-like activities of mPB in nanoparticles, apoM@mPB@Ra NPs obviously alleviated cellular hypoxia, thereby decreasing the expression of VEGF. Notably, in a mouse model of DR, intravitreally injected apoM@mPB@Ra NPs significantly improved the severity of the abnormal retinal vascular network and inflammatory microenvironment of retinopathy by down-regulating the expression of HIF-1α, VEGF, and inflammatory-related cytokines. Collectively, these findings demonstrate that apoM@mPB@Ra NPs provide a promising and effective approach for the treatment of DR.
糖尿病视网膜病变（DR）作为糖尿病最常见的微血管并发症，严重威胁糖尿病患者的视力。作为视网膜的常驻吞噬细胞，小胶质细胞参与DR的炎症、新生血管形成和神经退行性变。在此，报道了凋亡视网膜细胞膜包被、负载雷帕霉素的介孔普鲁士蓝纳米粒子作为免疫调节剂，通过调节小胶质细胞极化来改善DR。载脂蛋白M@介孔普鲁士蓝@雷帕霉素纳米粒子表现出良好的稳定性和生物相容性，由于凋亡膜上表达的“吃我”信号与小胶质细胞之间的特异性识别，实现了主动靶向递送。在脂多糖诱导的细胞炎症模型中，载脂蛋白M@介孔普鲁士蓝@雷帕霉素纳米粒子通过清除细胞内活性氧（ROS）并影响mTOR信号通路，有效促进小胶质细胞向抗炎表型（M2）极化，导致促炎细胞因子IL-6和TNF-α的下调。同时，由于纳米粒子中介孔普鲁士蓝的多酶样活性，载脂蛋白M@介孔普鲁士蓝@雷帕霉素纳米粒子明显减轻细胞缺氧，从而降低VEGF的表达。值得注意的是，在DR小鼠模型中，玻璃体内注射载脂蛋白M@介孔普鲁士蓝@雷帕霉素纳米粒子通过下调HIF-1α、VEGF和炎症相关细胞因子的表达，显著改善了视网膜病变异常视网膜血管网络和炎症微环境的严重程度。总的来说，这些发现表明载脂蛋白M@介孔普鲁士蓝@雷帕霉素纳米粒子为DR的治疗提供了一种有前景且有效的方法。
