Yoon Shin A, Hong So Jin, Han Jiyou, Lee Min Hee
Department of Chemistry, Chung-Ang University, Seoul 06974, Korea.
Department of Biomedical and Chemical Sciences, Hyupsung University, Hwasung-si 18330, Korea.
Anal Chem. 2024 Sep 11. doi: 10.1021/acs.analchem.4c03179.
Hypoxia is intricately associated with various diseases, including ischemia, vascular disorders, and cancer. Particularly in cancer cells, hypoxia promotes tumor growth, cell proliferation, migration, and invasion and enhances treatment resistance, making its detection crucial for cancer diagnosis and therapy. However, methods for detecting hypoxia are limited, often relying on single-detection systems. In this study, we developed a dual-lock-based fluorescent probe that selectively exhibits strong green fluorescence under hypoxic conditions due to simultaneous activity of nitroreductases (NTRs) and hydrogen sulfide (HS), with a high signal-to-background ratio. The biocompatibility and photophysical properties of the probes were thoroughly investigated through both extracellular and intracellular experimental analyses. Among the synthesized naphthalimide-based probes, the dual-detection probe demonstrated excellent selectivity and sensitivity to the simultaneous activity of NTR/HS compared to other single-detection probes. The performance of was applied to various organ-derived cancer cells and tumor tissue models such as HeLa cell sparoids, enabling spatiotemporal confocal fluorescence imaging and quantitative analysis of hypoxic levels in cancer. Our development of is expected to significantly advance cancer diagnosis and treatment by molecularly detecting hypoxia associated with cancer aggressiveness, therapy resistance, and unfavorable prognosis.
缺氧与多种疾病密切相关，包括缺血、血管疾病和癌症。特别是在癌细胞中，缺氧促进肿瘤生长、细胞增殖、迁移和侵袭，并增强治疗抗性，因此其检测对于癌症诊断和治疗至关重要。然而，检测缺氧的方法有限，通常依赖于单一检测系统。在本研究中，我们开发了一种基于双锁的荧光探针，由于硝基还原酶（NTRs）和硫化氢（HS）的同时作用，该探针在缺氧条件下选择性地呈现强烈的绿色荧光，具有高信噪比。通过细胞外和细胞内实验分析，对探针的生物相容性和光物理性质进行了全面研究。在合成的基于萘酰亚胺的探针中，与其他单一检测探针相比，双检测探针对NTR/HS的同时作用表现出优异的选择性和灵敏度。该探针的性能应用于各种器官来源的癌细胞和肿瘤组织模型，如HeLa细胞类球体，能够进行时空共聚焦荧光成像和癌症缺氧水平的定量分析。我们开发的该探针有望通过分子检测与癌症侵袭性、治疗抗性和不良预后相关的缺氧，显著推进癌症诊断和治疗。
