Institute of Drug Discovery Technology, Ningbo University, Ningbo, 315211, China.
Institute of Drug Discovery Technology, Ningbo University, Ningbo, 315211, China.
Talanta. 2024 Aug 15;276:126277. doi: 10.1016/j.talanta.2024.126277. Epub 2024 May 17.
Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet-triplet energy gap (ΔE), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with k/K as 2.18 × 10 M s. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.
硝基还原酶（NTR）是评估肿瘤缺氧水平的常用生物标志物。溶酶体作为主要的酶源之一，其功能障碍通常会导致各种疾病。在这项研究中，基于四苯基乙烯核心设计了一种 NTR 触发的溶酶体靶向探针 M-TPE-P。DFT 计算表明，该探针具有较窄的单重态-三重态能隙（ΔE），使其成为一种有效的光敏剂。M-TPE-P 与 NTR 的对接亲和力表明它们之间具有很强的结构匹配性。光物理性质表明，该探针在广泛的 pH 范围内对 NTR 具有高选择性和灵敏度，其 k/K 值为 2.18×10 M s。在 80% PBS/DMSO 溶液中的检测限为 53.6ng/mL。细胞成像研究表明，该探针可以用绿色荧光追踪细胞内 NTR 的行为。共定位分析表明其具有优异的溶酶体靶向特异性。此外，该探针在近红外照射后具有有效的 ROS 生成能力和显著的 PDT 效应，使其成为一种有前途的癌症治疗光敏剂。
