Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2023-11-23 DOI:10.1016/j.nano.2023.102725
Mengmeng Zhao MD , Jialing Guo PhD , Chaoying Tian MD , Mei Yan MD , Yingying Zhou MD , Chenxin Liu MD , Mengxue Pang MD , Bin Du Prof , Genyang Cheng Prof
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Abstract

Mitochondrial oxidative stress and inflammation are the main pathological features of acute kidney injury (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment of AKI. Here, the lipid micelle nanosystem modified with l-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified curcumin (Cur-TPP) and quercetin (Que). In the cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved renal function. Compared to mono-targeted group, the mitochondrial ROS content of renal tubular epithelial cells acting in the dual-target group decreased about 1.66-fold in vitro, serum creatinine (Scr) and urea nitrogen (BUN) levels were reduced by 1.5 and 1.2 mmol/L in vivo, respectively. Mechanistic studies indicated that the nanosystem inhibited the inflammatory response by interfering with the NF-κB and Nrf2 pathways. This study provides an efficient and low-toxicity strategy for AKI therapy.

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去除线粒体内外活性氧的双靶向纳米颗粒治疗急性肾损伤。
线粒体氧化应激和炎症是急性肾损伤(AKI)的主要病理特征。然而,抗炎药物的全身毒性和抗氧化剂的低生物利用度限制了AKI的治疗。本研究设计了l-丝氨酸修饰的脂质胶束纳米系统,以改善AKI的治疗。用胶束包覆抗氧化药物4-羧基丁基三苯基溴化膦改性姜黄素(Cur-TPP)和槲皮素(Que)。在顺铂(CDDP)诱导的AKI模型中,纳米系统保护线粒体结构并改善肾功能。与单靶点组相比,双靶点组肾小管上皮细胞线粒体ROS含量在体外降低约1.66倍,体内血清肌酐(Scr)和尿素氮(BUN)水平分别降低1.5和1.2 mmol/L。机制研究表明,纳米系统通过干扰NF-κB和Nrf2通路抑制炎症反应。本研究为AKI治疗提供了一种高效、低毒的策略。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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