Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia–reperfusion injury

<b>Aim:</b> To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia–reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc–tannic acid nanozyme (ZnTA). <b>Materials &amp; methods:</b> After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity. <b>Results:</b> Malondialdehyde, Fe²⁺ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn²⁺ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition. <b>Conclusion:</b> This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI. In this study, zinc–tannic acid nanozyme (ZnTA) was synthesized using natural plant polyphenol tannic acid. This study explored the morphological characteristics of ZnTA in detail. ZnTA has excellent reactive oxygen species scavenging effect. ZnTA was observed to effectively inhibit ferroptosis in both <i>in vitro</i> and <i>in vivo</i> experiments. The morphological characteristics of mitochondria after ZnTA treatment were examined using electron microscopy. Zn²⁺ in ZnTA inhibited the expression of caspase 3 and 9. Apoptosis inhibition was observed after ZnTA treatment. ZnTA can effectively alleviate renal IRI.