Liu Chang, Cao Zhengjiang, Li Li, Li Qingyin, Zhang Chunle, Wang Yunbing, Li Linhua, Fu Ping
Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
Institute of Clinical Pathology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
ACS Biomater Sci Eng. 2025 Jan 13;11(1):383-401. doi: 10.1021/acsbiomaterials.4c01852. Epub 2024 Dec 16.
Sepsis is a severe and complex systemic infection that can result in multiple organ dysfunction. Sepsis-associated acute kidney injury (SAKI), caused by inflammatory response, oxidative stress, and cellular apoptosis, is a common complication that seriously impacts patient survival rates. Herein, a potent and novel metal-polyphenol nanomicelle can be efficiently self-assembled with Pt and honokiol (HK) by the chelation, π-π conjugation, hydrophobic action, and the surfactant properties of Tween-80. These nanomicelles not only enhance drug bioavailability (encapsulation rates: Pt─49%, HK─70%) and reduce drug toxicity (safety dose: <20 μg/g) but also improve targeting toward damaged renal tissues. Furthermore, Pt and HK in the nanomicelles exert a synergistic physiological effect by scavenging free radicals to alleviate oxidative damage, inhibiting macrophage activation and the release of inflammatory factors to regulate inflammation, and displaying broad-spectrum antimicrobial activity to control infection. These actions collectively protect renal tissue and restore its functionality. Here, we constructed metal-polyphenol nanomicelles (Pt/HK-NMs) via ingenious and efficient self-assembly, providing a new strategy to compensate for deficiencies in the hemodialysis and antibiotic treatment of SAKI.
脓毒症是一种严重且复杂的全身感染，可导致多器官功能障碍。由炎症反应、氧化应激和细胞凋亡引起的脓毒症相关急性肾损伤（SAKI）是一种常见并发症，严重影响患者生存率。在此，一种强效且新型的金属 - 多酚纳米胶束可通过Tween - 80的螯合、π - π共轭、疏水作用和表面活性剂性质与铂（Pt）和厚朴酚（HK）高效自组装而成。这些纳米胶束不仅提高药物生物利用度（包封率：Pt─49%，HK─70%）并降低药物毒性（安全剂量：<20 μg/g），还改善对受损肾组织的靶向性。此外，纳米胶束中的Pt和HK通过清除自由基以减轻氧化损伤、抑制巨噬细胞活化和炎症因子释放以调节炎症以及展现广谱抗菌活性以控制感染，发挥协同生理效应。这些作用共同保护肾组织并恢复其功能。在此，我们通过巧妙且高效的自组装构建了金属 - 多酚纳米胶束（Pt/HK - NMs），为弥补SAKI血液透析和抗生素治疗的不足提供了一种新策略。
