# Renal-tubular-mitochondrial sequentially targeted nanoagent breaks the vicious cycle of oxidative stress and mtDNA-driven inflammation in acute kidney injury therapy

## TL;DR

A new nanoagent targets kidney cells and mitochondria to break a harmful cycle of damage and inflammation in acute kidney injury, offering a promising new treatment approach.

## Contribution

A cascade-targeted nanotherapeutic agent that simultaneously clears oxidative stress and prevents mitochondrial DNA leakage in acute kidney injury.

## Key findings

- The STMB nanoagent effectively delivers to damaged renal tubular epithelial cells via kidney injury molecule 1.
- The dual-channel intervention terminates the cycle of oxidative damage and inflammation in AKI models.
- This strategy transitions AKI treatment from passive care to active cellular repair.

## Abstract

Acute kidney injury (AKI) is a life-threatening disorder that is responsible for 1.7 million deaths each year. Current treatment strategies, such as renal replacement therapy and supportive care, remain ineffective in reversing tubular damage in 20–50% of patients, largely due to their inability to promptly restore renal tubular epithelial cells function. The present study developed a cascade-targeted core-shell nanotherapeutic agent STMB with L-serine shell that enables precise kidney injury molecule 1-mediated delivery to damaged RTECs, while tannic acid core facilitates mitochondrial localization. Tannic acid continuously scavenges reactive oxygen species. By simultaneously clearing reactive oxygen species and preventing mitochondrial DNA leakage by STMB, this dual-channel intervention successfully terminates the self-amplifying cycle of oxidative damage and inflammatory signaling, resulting in therapeutic effects in both cisplatin-induced and ischemia-reperfusion AKI models. This strategy redefines AKI therapeutics by transitioning from passive symptom management to active cellular repair, which fills a critical void in clinical nephrology and opens new avenues for organ-protective nanomedicine development in critical care settings.

The online version contains supplementary material available at 10.1186/s12951-026-04049-2.