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一种由FA1位点识别的自组装荧光纳米探针,用于特异性选择人血清白蛋白:其在血红素检测、细胞成像和荧光追踪药物递送中的应用。

A self-assembled fluorescent nanoprobe recognized by FA1 site for specifically selecting HSA: Its applications in hemin detection, cell imaging and fluorescent tracing drug delivery.

作者信息

Ding Bo-Wen, Sang Ruo-Xi, Li Xiao-Yu, Fan Jing, Tian Yu, Ma Ying, Xie Cheng-Zhi, Xu Jing-Yuan, Feng Yu-Kuan

机构信息

Pancreas Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Department of Breast Oncoplastic and reconstructive Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China.

Department of Chemical Biology and Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.

出版信息

Bioorg Chem. 2025 Jan;154:108120. doi: 10.1016/j.bioorg.2024.108120. Epub 2024 Dec 31.

Abstract

As naturally essential biomacromolecule, HSA has become diagnostic indicators for various diseases and universal carriers for anticancer drug delivery, therefore, fluorescence detection and labeling for HSA possess significant application value in the biomedical field. In this paper, hydrazide Schiff base fluorescent probe NDQC was designed and synthesized, which self-assembled into nanoparticles in aqueous solution system and demonstrated excellent selectivity and sensitivity towards HSA. Through displacement assay and molecular docking simulation, the binding of NDQC with HSA in FA1 site was demonstrated, thereby no obvious fluorescence signal presented for homologous protein BSA due to their structural differences in binding site. Non-toxic probe NDQC is suitable for the fluorescence imaging of HSA in cells, and colocalization fluorescence images showed that NDQC-HSA could illuminate mitochondria. Based on the pH sensitivity of fluorescence emission for NDQC-HSA, discrimination of cancer cells and normal cells could be achieved. For practical applications, NDQC-HSA can be employed to measure the content of hemin. More importantly, NDQC could fluorescently label HSA and therefore NDQC-HSA complex act as the carrier for loading cisplatin. The present findings demonstrate that the probe NDQC has potential in exploring HSA at cellular levels and hold great promise in application of tracking drug-loading nanoparticles.

摘要

作为天然必需的生物大分子,人血清白蛋白(HSA)已成为多种疾病的诊断指标和抗癌药物递送的通用载体,因此,对HSA的荧光检测和标记在生物医学领域具有重要的应用价值。本文设计合成了酰肼席夫碱荧光探针NDQC,其在水溶液体系中自组装成纳米颗粒,对HSA表现出优异的选择性和灵敏度。通过置换实验和分子对接模拟,证明了NDQC与HSA在FA1位点的结合,由于同源蛋白牛血清白蛋白(BSA)在结合位点的结构差异,其未呈现明显的荧光信号。无毒探针NDQC适用于细胞内HSA的荧光成像,共定位荧光图像显示NDQC-HSA可照亮线粒体。基于NDQC-HSA荧光发射的pH敏感性,可实现癌细胞与正常细胞的区分。在实际应用中,NDQC-HSA可用于测定血红素的含量。更重要的是,NDQC可对HSA进行荧光标记,因此NDQC-HSA复合物可作为负载顺铂的载体。本研究结果表明,探针NDQC在细胞水平上探索HSA方面具有潜力,在跟踪载药纳米颗粒的应用中具有广阔前景。

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