Lysosome-targeted dual-locked NIR fluorescent probe for visualization of H2S and viscosity in drug-induced liver injury and tumor models

IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL
Jingcan Qin , Fei Kong , Jie Huang , Bang Xiao , Yun Bian , Chengwei Shao
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Abstract

Background

Lysosomes, as an indispensable subcellular organelle have numerous physiological functions closely associated with H2S and viscosity, and accurate assessment of H2S/viscosity fluctuations in lysosomes is essential for gaining a comprehensive understanding of lysosome-related physiological activities and pathological processes. The previous single-response fluorescent probes for either H2S or viscosity alone have the potential to generate "false positive" signals in a complex biological environment. In contrast, dual-locked probes can simultaneously respond to multiple targets simultaneously, which could effectively eliminate this defect. Therefore, it is essential to constructed a lysosome-targeted dual-locked NIR fluorescent probe for imaging H2S and viscosity.

Results

In this study, we developed a lysosome-targeted dual-locked NIR fluorescent probe (LFP-N3) for imaging H2S and viscosity based on an integrated ICT-TICT process. In the presence of both H2S and high viscosity conditions, the azide moiety of LFP-N3 reacts with H2S, resulting in the formation of LFP-NH2 that facilitates the ICT process; high viscosity condition further restricts the chemical bond rotation of LFP-NH2, which suppresses the TICT process. As a result, the fluorescence signal of LFP-N3 is significantly enhanced at 690 nm with a large Stokes shift (190 nm). Cytotoxicity assay and colocalization experiments in living cells indicated LFP-N3 possessed low cytotoxicity and precise lysosome-targeted capability. Moreover, both in vitro and in vivo experiments further validated that the fluorescence signal of LFP-N3 can be triggered by the presence of both H2S and high viscosity in tumor and drug-induced liver injury models.

Significance

The lysosome-targeted dual-locked NIR fluorescent probe has been successfully utilized to imaging H2S and viscosity in vitro and in vivo. Compared with the single-response fluorescent probes, the dual-locked NIR probe (LFP-N3) could effectively mitigate false-positive signals and increase spatial resolution, and has great potential to be developed as a novel diagnostic agent for lysosome-related diseases.

Abstract Image

Abstract Image

溶酶体靶向双锁定近红外荧光探针用于药物性肝损伤和肿瘤模型中H2S和黏度的可视化
溶酶体作为一种不可缺少的亚细胞器,具有许多与H2S和黏度密切相关的生理功能,准确评估溶酶体中H2S/黏度的波动对于全面了解溶酶体相关的生理活动和病理过程至关重要。在复杂的生物环境中,以往针对H2S或粘度的单响应荧光探针有可能产生“假阳性”信号。而双锁探头可以同时响应多个目标,有效地消除了这一缺陷。因此,构建以溶酶体为靶点的双锁定近红外荧光探针对H2S和黏度进行成像是十分必要的。结果本研究基于ICT-TICT集成工艺,开发了一种针对溶酶体的双锁定近红外荧光探针(LFP-N3),用于对H2S和粘度进行成像。在H2S和高粘度条件下,LFP-N3的叠氮化物部分与H2S反应,生成有利于ICT过程的LFP-NH2;高粘度条件进一步限制了LFP-NH2的化学键旋转,抑制了TICT过程。结果表明,LFP-N3在690 nm处荧光信号明显增强,Stokes位移较大(190 nm)。细胞毒性实验和活细胞共定位实验表明,LFP-N3具有低细胞毒性和精确的溶酶体靶向能力。此外,体外和体内实验进一步验证了在肿瘤和药物性肝损伤模型中,H2S和高黏度均可触发LFP-N3的荧光信号。意义溶酶体靶向双锁定近红外荧光探针已成功用于体外和体内的H2S和黏度成像。与单响应荧光探针相比,双锁定近红外探针(LFP-N3)可有效减轻假阳性信号,提高空间分辨率,具有开发溶酶体相关疾病新诊断试剂的潜力。
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来源期刊
Analytica Chimica Acta
Analytica Chimica Acta 化学-分析化学
CiteScore
10.40
自引率
6.50%
发文量
1081
审稿时长
38 days
期刊介绍: Analytica Chimica Acta has an open access mirror journal Analytica Chimica Acta: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Analytica Chimica Acta provides a forum for the rapid publication of original research, and critical, comprehensive reviews dealing with all aspects of fundamental and applied modern analytical chemistry. The journal welcomes the submission of research papers which report studies concerning the development of new and significant analytical methodologies. In determining the suitability of submitted articles for publication, particular scrutiny will be placed on the degree of novelty and impact of the research and the extent to which it adds to the existing body of knowledge in analytical chemistry.
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