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
{"title":"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。","authors":"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","doi":"10.1016/j.nano.2023.102725","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Mitochondrial oxidative stress and inflammation are the main pathological features of </span>acute kidney injury<span> (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment<span><span> of AKI. Here, the lipid<span> micelle </span></span>nanosystem modified with </span></span></span><span>l</span><span><span><span><span>-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified </span>curcumin<span><span> (Cur-TPP) and quercetin (Que). In the </span>cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved </span></span>renal function<span>. 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, </span></span>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.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment\",\"authors\":\"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\",\"doi\":\"10.1016/j.nano.2023.102725\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>Mitochondrial oxidative stress and inflammation are the main pathological features of </span>acute kidney injury<span> (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment<span><span> of AKI. Here, the lipid<span> micelle </span></span>nanosystem modified with </span></span></span><span>l</span><span><span><span><span>-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified </span>curcumin<span><span> (Cur-TPP) and quercetin (Que). In the </span>cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved </span></span>renal function<span>. 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, </span></span>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.</span></p></div>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2023-11-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S154996342300076X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S154996342300076X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment
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.
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.