A pH‐Responsive Biomimetic Antioxidant Nanoplatform with Dual Renal Targeting for Synergistic Therapy of Acute Kidney Injury

作者：Shichao Zhang, Yuhan Xie, Longchao Zhang, Yuanjiong Qi, Quan Liao, Chenglong Xu, Shushuai Yang, Haiwen Zhou, Qidan Tan, Shiyong Qi · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202515664 · 被引用次数：9 · 研究领域：Acute Kidney Injury Research、Nanoplatforms for cancer theranostics、Chemotherapy-induced organ toxicity mitigation

Abstract Acute kidney injury (AKI) represents a critical clinical condition marked by abrupt deterioration of renal function, primarily driven by oxidative stress, inflammation, and apoptosis. However, effective targeted therapies remain limited. Here, a smart, biomimetic nanoplatform (CeAst@MK) that synergistically addresses oxidative and inflammatory injury in AKI is reported. CeAst nanoparticles are formed via coordination between Ce 3 ⁺ ions and astragalin (Ast), a natural flavonoid with intrinsic ROS‐scavenging and anti‐inflammatory properties. To enhance immune evasion and renal targeting specificity, CeAst is cloaked with macrophage membranes (MCM) and modified with a kidney‐targeting peptide (KTP), yielding the final CeAst@MK system. The platform exhibits pH‐responsive release in the acidic microenvironment of injured renal tissues, enabling precise and rapid therapeutic delivery. In both LPS‐ and ischemia reperfusion‐induced AKI models, CeAst@MK significantly improves renal function, suppresses proinflammatory cytokines, and promotes M2 macrophage polarization. Mechanistically, it modulates PI3K/Akt and NF‐κB pathways, achieving dual antioxidative and anti‐inflammatory effects. This study presents a translationally promising nanotherapeutic system integrating natural antioxidants, biomimetic camouflage, and tissue‐specific delivery, offering an effective and precise strategy for AKI intervention.