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

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

  • Biomaterials. 2025 Dec 18:329:123933. doi: 10.1016/j.biomaterials.2025.123933.
Lili Huang 1,  Pengfei Yang 1,  Chenli Zhang 2,  Ling Tan 3,  Lingshan Zhao 2,  Liling Yang 4,  Ling Zhang 5,  Zheng Zhang 6,  Jun Deng 7,  Xiaohui Liao 8
Affiliations

Affiliations

  • 1 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Kuanren Laboratory of Translational Lipidology, Centre for Lipid Research, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
  • 2 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Nephrology, Second People's Hospital of Yibin, Yibin, 644000, China.
  • 3 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Gastroenterology, Second People's Hospital of Yibin, Yibin, 644000, China.
  • 4 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Nephrology, Mianyang Central Hospital, Mianyang, 621000, China.
  • 5 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • 6 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, 400010, China.
  • 7 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China. Electronic address: [email protected].
  • 8 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address: [email protected].
PMID: 41435454 DOI: 10.1016/j.biomaterials.2025.123933
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.

Keywords

Acute kidney injury; Mitochondrial repair; Nanomedicine; Sequential targeting strategy.

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