Sequential-targeting nanomedicine protects against acute kidney injury by modulating calcium influx and scavenging reactive oxygen species.

Abstract

Acute kidney injury (AKI) is a global health challenge responsible for approximately 1.7 million deaths each year. Current treatment options, such as renal replacement therapy and supportive care, are limited to systemic support and fail to promote repair of dysfunctional renal tubular epithelial cells (RTECs). In this study, we developed a macrophage membrane-coated sequential-targeting nanodrug, MA-5@MΦ-LSALT, which leverages the LSALT targeting peptide to selectively deliver the nanodrug to injured RTECs. Upon reaching the damaged RTECs, the released mitochonic acid-5 (MA-5) further localizes to mitochondria. In both cisplatin-induced and ischemia-reperfusion AKI models, MA-5@MΦ-LSALT inhibited calcium influx and reduced reactive oxygen species levels. Collectively, this work introduces an innovative sequential-targeting strategy from kidneys to RTECs to mitochondria that effectively addresses the challenge of targeted repair in AKI and highlights a promising therapeutic avenue for clinical translation.