Tao Hui, Guo Jiawei, Ma Yongchang, Zhao Yang, Jin Taotao, Gu Lijuan, Dou Yin, Liu Jinyi, Hu Houyuan, Xiong Xiaoxing, Zhang Jianxiang
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430006, China.
ACS Nano. 2020 Sep 22;14(9):11083-11099. doi: 10.1021/acsnano.0c00539. Epub 2020 Aug 17.
Liver injury can result in different hepatic diseases such as fatty liver, liver fibrosis, hepatitis, and liver failure, which are mainly responsible for global mortality and morbidity. Early diagnosis is critical for the treatment of liver diseases. Herein we report luminescence imaging of neutrophil-mediated acute liver injury, including alcoholic liver injury (ALI) and acute liver failure (ALF). To this purpose, a biodegradable luminescent material was developed by chemical functionalization of a cyclic oligosaccharide, which can be produced into nanoprobes (defined as LaCD NPs). Luminescence of LaCD NPs was dependent on the level of reactive oxygen species and myeloperoxidase (MPO). Correspondingly, activated neutrophils could be specifically imaged by LaCD NPs, and the luminescent signal was positively associated with the neutrophil count. In mouse models of ALI and ALF, LaCD NPs enabled precise quantification and tracking of neutrophils in livers. In both cases, changes in the luminescence intensity are consistent with time-dependent profiles of neutrophils, MPO, and other parameters relevant to the pathogenesis of liver injury. Moreover, the luminescence imaging capacity of LaCD NPs can be additionally improved by surface functionalization with a neutrophil-targeting peptide. In addition, preliminary and studies demonstrated good safety of LaCD NPs. Consequently, LaCD NPs can be further developed as an effective and biocompatible luminescent nanoprobe for dynamic detection of the development of neutrophil-mediated acute liver injury. It is also promising for diagnosis of other neutrophil-associated liver diseases.
肝损伤可导致不同的肝脏疾病，如脂肪肝、肝纤维化、肝炎和肝衰竭，这些疾病是全球死亡率和发病率的主要原因。早期诊断对肝脏疾病的治疗至关重要。在此，我们报告了中性粒细胞介导的急性肝损伤的发光成像，包括酒精性肝损伤（ALI）和急性肝衰竭（ALF）。为此，通过对环糊精进行化学功能化开发了一种可生物降解的发光材料，该材料可制成纳米探针（定义为LaCD NPs）。LaCD NPs的发光取决于活性氧和髓过氧化物酶（MPO）的水平。相应地，活化的中性粒细胞可以被LaCD NPs特异性成像，并且发光信号与中性粒细胞计数呈正相关。在ALI和ALF的小鼠模型中，LaCD NPs能够精确量化和追踪肝脏中的中性粒细胞。在这两种情况下，发光强度的变化与中性粒细胞、MPO以及与肝损伤发病机制相关的其他参数的时间依赖性变化一致。此外，通过用中性粒细胞靶向肽进行表面功能化可以进一步提高LaCD NPs的发光成像能力。此外，初步研究证明了LaCD NPs具有良好的安全性。因此，LaCD NPs可以进一步开发成为一种有效且生物相容的发光纳米探针，用于动态检测中性粒细胞介导的急性肝损伤的发展。它在诊断其他与中性粒细胞相关的肝脏疾病方面也很有前景。
