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

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bo-Wen Ding , Ruo-Xi Sang , Xiao-Yu Li , Jing Fan , Yu Tian , Ying Ma , Cheng-Zhi Xie , Jing-Yuan Xu , Yu-Kuan Feng
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引用次数: 0

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.

Abstract Image

一种FA1位点识别的自组装荧光纳米探针:在血红蛋白检测、细胞成像和荧光示踪药物传递中的应用
HSA作为天然必需的生物大分子,已成为多种疾病的诊断指标和抗癌药物传递的通用载体,因此对HSA进行荧光检测和标记在生物医学领域具有重要的应用价值。本文设计并合成了肼基希夫碱荧光探针NDQC,该探针在水溶液体系中自组装成纳米颗粒,对HSA具有优异的选择性和灵敏度。通过位移实验和分子对接模拟,证实NDQC与HSA在FA1位点结合,由于结合位点的结构差异,同源蛋白BSA没有明显的荧光信号。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可以照亮线粒体。根据NDQC-HSA荧光发射的pH敏感性,可以实现癌细胞和正常细胞的区分。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可以荧光标记HSA,因此NDQC-HSA复合物可以作为装载顺铂的载体。目前的研究结果表明,NDQC探针在细胞水平上具有探索HSA的潜力,并且在追踪载药纳米颗粒方面具有很大的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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