A Strontium‐Based Polyphenol Nanozyme Reverses Cisplatin‐Related Acute Kidney Injury Through Near‐Infrared‐Enhanced PI3K/AKT Pathway Inhibition and Macrophage M2 Directional Polarization

Abstract

Cisplatin‐related acute kidney injury (CP‐AKI) is a serious complication of cisplatin (CP) treated patients with cancer with high morbidity and mortality rates. It is directly related to the abnormal accumulation of CP in renal tubular epithelial cells, causing metabolic toxicity, DNA damage, and oxidative stress. Herein, we developed a polyphenol nanozyme (SrEG) by the coordination of strontium ions (Sr 2+ ) and epigallocatechin gallate. It was demonstrated that SrEG, combined with NIR irradiation, exhibited excellent capabilities of scavenging various types of reactive oxygen species (ROS). It was also determined that SrEG + NIR efficiently eliminated intracellular ROS levels, inhibited inflammation related cytokines expression, and induced macrophage M2 directional polarization, thus preventing cellular damage. By intravenous (IV) administration, SrEG was efficiently accumulated in the kidney and gradually degraded. Accordingly, the administration of SrEG + NIR offered the perfect therapeutic effects in CP‐AKI rats by inhibiting the PI3K/AKT pathway, thus accelerating kidney function repair. Overall, the strategy of SrEG + NIR showed substantial clinical promise as a potential therapeutic strategy in ROS‐related diseases.