State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
J Mater Chem B. 2024 Jun 12;12(23):5609-5618. doi: 10.1039/d4tb00382a.
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.
细胞焦亡是一种促炎的程序性细胞死亡方式，它可能成为减轻药物诱导急性肾损伤（AKI）的潜在治疗靶点。然而，目前尚无有效的、针对肾脏的细胞焦亡抑制剂用于 AKI 的治疗。在此，我们报道了一种源自 3,4',5-三羟基二苯乙烯的具有药理活性的碳化纳米抑制剂（P-RCDs），它可以通过抑制细胞焦亡来优先在肾脏蓄积，并改善化疗药物诱导的 AKI。特别是，这种碳化纳米制剂可以将所需的细胞焦亡抑制活性和自由基清除活性转移到纳米尺度，使 P-RCDs 具有良好的肾脏靶向能力。在顺铂诱导的 AKI 小鼠中，P-RCDs 不仅可以在肾脏细胞中高效地抑制 GSDME 介导的细胞焦亡，而且具有很高的抗氧化活性，可以保护肾脏免受氧化损伤。本研究提出了一种可行且有效的策略，用于构建多功能碳化纳米医学，以实现所需药理活性的靶向递送。
