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 Feb 2024
Accepted
06 May 2024
First published
07 May 2024

J. Mater. Chem. B, 2024, Advance Article

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, Advance Article , DOI: 10.1039/D4TB00382A

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