Scholarlink

<p>Bioorthogonal chemistry-mediated self-assembly holds great promise for dynamic molecular imaging in living organisms. However, existing approaches are limited to nanoaggregates with ‘always-on’ signals, suffering from high signal-to-background ratio (SBR) and compromised detection sensitivity. Herein we report a nitrile-aminothiol (NAT) bioorthogonal fluorogenic probe (<b>CyNA</b><sub><b>P</b></sub><b>-SS-FK</b>) for ultrasensitive diagnosis of orthotopic hepatocellular carcinoma. This probe comprises a nitrile-substituted hemicyanine scaffold with a cysteine tail dually locked with biomarker-responsive moieties. Upon dual cleavage by tumor-specific cathepsin B and biothiols, the 1,2-aminothiol residue is exposed and spontaneously reacts with nitrile group for in situ intramolecular macrocyclization, enabling near-infrared fluorescence (NIRF) turn-on as well as self-assembly. In living male mice, such ‘cleavage-click-assembly’ regimen allows for real-time and ultrasensitive detection of small cancerous lesions (~2 mm in diameter) with improved SBR (~5) and extended detection window (~36 h), outperforming conventional clinical assays. This study not only presents NAT click reaction-based fluorogenic probes but also highlights a generic dual-locked design of these probes.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Nitrile-aminothiol bioorthogonal near-infrared fluorogenic probes for ultrasensitive in vivo imaging

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月2日

查看全文
  • Weiping Xu,
  • Shujuan Yi,
  • Jie Liu,
  • Yuyan Jiang,
  • Jiaguo Huang

摘要

Bioorthogonal chemistry-mediated self-assembly holds great promise for dynamic molecular imaging in living organisms. However, existing approaches are limited to nanoaggregates with ‘always-on’ signals, suffering from high signal-to-background ratio (SBR) and compromised detection sensitivity. Herein we report a nitrile-aminothiol (NAT) bioorthogonal fluorogenic probe (CyNAP-SS-FK) for ultrasensitive diagnosis of orthotopic hepatocellular carcinoma. This probe comprises a nitrile-substituted hemicyanine scaffold with a cysteine tail dually locked with biomarker-responsive moieties. Upon dual cleavage by tumor-specific cathepsin B and biothiols, the 1,2-aminothiol residue is exposed and spontaneously reacts with nitrile group for in situ intramolecular macrocyclization, enabling near-infrared fluorescence (NIRF) turn-on as well as self-assembly. In living male mice, such ‘cleavage-click-assembly’ regimen allows for real-time and ultrasensitive detection of small cancerous lesions (~2 mm in diameter) with improved SBR (~5) and extended detection window (~36 h), outperforming conventional clinical assays. This study not only presents NAT click reaction-based fluorogenic probes but also highlights a generic dual-locked design of these probes.