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一种用于结直肠癌精确诊断和病理评估的硫化氢激活近红外二区成像探针。

A H2S-activated NIR-II imaging probe for precise diagnosis and pathological evaluation of colorectal tumor.

作者信息

Ji Yu, Huang Qinxian, Jia Qian, Yan Haohao, Chi Yajing, Jia Yuanyuan, Qiao Chaoqiang, Feng Yanbin, Yang Zuo, Zhang Ruili, Wang Zhongliang

机构信息

Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, P. R. China.

Department of Neurogastroenterology and Pelvic Floor Surgery, Hospital of Gastroenterology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, 710100, P. R. China.

出版信息

Theranostics. 2025 Jan 1;15(1):189-201. doi: 10.7150/thno.103999. eCollection 2025.

Abstract

The quick and accurate detection of colorectal cancer (CRC) is essential for improving the treatment efficacy and patient survival, which nevertheless remains challenging due to low specificity and sensitivity of current CRC diagnostic approaches. Therefore, providing a robust solution for real-time and accurate tumor delineation is highly desirable. We report a novel polyacrylic acid-mediated strategy to develop the endogenous hydrogen sulfide (HS)-activated NIR-II probe DCNP@PB for specific visualization of CRC and image-guided tumor surgery. The stability, biocompatibility, HS-responsiveness, and NIR-II imaging capability were evaluated and . Human CRC tissues were used to evaluated the performance of the DCNP@PB. By exploiting the effective inner filter effect (IFE) and fluorescence resonance energy transfer (FRET) between DCNPs and PB, luminescence of DCNP@PB can be rapidly switched ON in response to HS in colorectal tumor, affording high tumor-to-background ratio (TBR). Notably, HS-responsive range of DCNP@PB well matches the HS concentration at tumor site, thereby minimizing nonspecific activation by other sulfur-containing substances in a complicated biological environment. Such accurate HS responsiveness not only benefits the differentiation between tumor and normal tissues in the mouse model, but also clearly delineates the cancerous boundaries in human tissues specimens. This work presents not only a promising example of HS-activated NIR-II optical probe that could be intravenously injected for applications to afford reliable information and quick feedback, but also an effective strategy to design the activatable imaging probes for precise tumor diagnosis and intraoperative decision support.

摘要

快速准确地检测结直肠癌(CRC)对于提高治疗效果和患者生存率至关重要,然而,由于当前CRC诊断方法的特异性和敏感性较低,这一检测仍然具有挑战性。因此,提供一种强大的实时准确肿瘤勾勒解决方案非常必要。我们报告了一种新型的聚丙烯酸介导策略,用于开发内源性硫化氢(HS)激活的近红外二区(NIR-II)探针DCNP@PB,用于结直肠癌的特异性可视化和图像引导的肿瘤手术。评估了其稳定性、生物相容性、HS响应性和NIR-II成像能力。使用人CRC组织评估DCNP@PB的性能。通过利用DCNPs与PB之间有效的内滤光效应(IFE)和荧光共振能量转移(FRET),DCNP@PB的发光可在结直肠肿瘤中对HS作出响应而迅速开启,从而提供高肿瘤与背景比率(TBR)。值得注意的是,DCNP@PB的HS响应范围与肿瘤部位的HS浓度非常匹配,从而最大限度地减少了复杂生物环境中其他含硫物质的非特异性激活。这种精确的HS响应性不仅有利于在小鼠模型中区分肿瘤组织和正常组织,还能清晰勾勒出人体组织标本中的癌边界。这项工作不仅展示了一种有前景的HS激活的NIR-II光学探针实例,该探针可静脉注射用于提供可靠信息和快速反馈的应用,还展示了一种设计可激活成像探针用于精确肿瘤诊断和术中决策支持的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fc9/11667233/d3d8987aa638/thnov15p0189g001.jpg

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