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透明质酸包覆的醇溶蛋白纳米粒介导的白藜芦醇疗法用于减少顺铂相关性肾毒性。

Hyaluronic acid-coated zein nanoparticle-mediated resveratrol therapy for the reduction of cisplatin-associated nephrotoxicity.

机构信息

Department of Kidney Transplantation and Dialysis Center, The Second People's Hospital of Shanxi Province, Taiyuan, Shanxi, 030012, China.

Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, China.

出版信息

Biochem Biophys Res Commun. 2024 Dec 3;736:150873. doi: 10.1016/j.bbrc.2024.150873. Epub 2024 Oct 22.

Abstract

Cisplatin (CDDP) is commonly used as an anticancer drug in clinical practice, but severe nephrotoxicity restricts it from exerting anticancer effects. Natural drugs, such as resveratrol, can alleviate the side effects of cisplatin, but their low solubility and gastrointestinal effects prevent them from working. Herein, we developed nanoparticles for kidney injury consisting of a biocompatible material, zein, as a carrier. HA-Zein/Res NPs were fabricated using low-molecular-weight hyaluronic acid coatings. This preparation is non-cytotoxic to renal tubular epithelial cells and can be used with confidence. Low-molecular-weight hyaluronic acid has inflammation-targeting properties and CDDP damage causes renal inflammation. Owing to this property of the low-molecular-weight hyaluronic acid coating, in vivo imaging experiments in mice demonstrated that the HA-Zein/Res NPs enabled more nanoparticles to accumulate in the renal sites affected by inflammation. Efficient resveratrol delivery alleviated kidney injury, and experiments demonstrated that HA-Zein/Res NPs could treat kidney injury while reducing the serum creatinine and urea nitrogen levels in mice. Collectively, these results indicated that this nanomaterial is a promising agent for reducing the clinical nephrotoxicity of cisplatin.

摘要

顺铂(CDDP)在临床实践中常被用作抗癌药物,但严重的肾毒性限制了其抗癌作用。天然药物,如白藜芦醇,可以减轻顺铂的副作用,但它们的低溶解度和胃肠道作用阻止了它们的应用。在这里,我们开发了一种由生物相容性材料玉米醇溶蛋白作为载体的用于肾损伤的纳米颗粒。HA-Zein/Res NPs 是通过使用低分子量透明质酸涂层制备的。这种制剂对肾小管上皮细胞没有细胞毒性,可以放心使用。低分子量透明质酸具有炎症靶向特性,CDDP 损伤会引起肾脏炎症。由于低分子量透明质酸涂层的这种特性,在小鼠的体内成像实验中,证明了 HA-Zein/Res NPs 能够使更多的纳米颗粒聚集在受炎症影响的肾脏部位。高效白藜芦醇的传递减轻了肾损伤,实验表明,HA-Zein/Res NPs 可以在降低小鼠血清肌酐和尿素氮水平的同时治疗肾损伤。总之,这些结果表明,这种纳米材料是一种有前途的减少顺铂临床肾毒性的药物。

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