Issue 23, 2024

Targeted inhibition of pyroptosis via a carbonized nanoinhibitor for alleviating drug-induced acute kidney injury

Abstract

Pyroptosis is a form of pro-inflammatory programmed cell death and it represents a potential therapeutic target for alleviating drug-induced acute kidney injury (AKI). However, there is a lack of effective and kidney-targeted pyroptosis inhibitors for AKI treatment so far. Herein, we report a pharmacologically active carbonized nanoinhibitor (P-RCDs) derived from 3,4′,5-trihydroxystilbene that can preferentially accumulate in the kidneys and ameliorate chemotherapeutic drug-induced AKI by inhibiting pyroptosis. In particular, such a carbonized nanoformulation enables the transfer of desired pyroptosis inhibitory activity as well as the radical eliminating activity to the nanoscale, endowing P-RCDs with a favorable kidney-targeting ability. In cisplatin-induced AKI mice, P-RCDs can not only pharmacologically inhibit GSDME-mediated pyroptosis in renal cells with high efficacy, but also exhibit high antioxidative activity that protects the kidneys from oxidative injury. The present study proposes a feasible but efficacious strategy to construct versatile carbonized nanomedicine for targeted delivery of the desired pharmacological activities.

Graphical abstract: Targeted inhibition of pyroptosis via a carbonized nanoinhibitor for alleviating drug-induced acute kidney injury

Supplementary files

Article information

Article type
Paper
Submitted
23 2 2024
Accepted
06 5 2024
First published
07 5 2024

J. Mater. Chem. B, 2024,12, 5609-5618

Targeted inhibition of pyroptosis via a carbonized nanoinhibitor for alleviating drug-induced acute kidney injury

Y. Ji, H. Wang, X. Liu, Z. Zhu, A. Song, L. Chen and J. Ren, J. Mater. Chem. B, 2024, 12, 5609 DOI: 10.1039/D4TB00382A

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