Lam Kristy W K, Zhang Yaojia, Du Wutong, Sun Jie, Sun Feiyi, Chen Yuyang, Ma Charlie C H, Lam Jacky W Y, Kwok Ryan T K, Sun Jianwei, He Xuewen, Tang Ben Zhong
Department of Chemistry, Department of Chemical and Biological Engineering, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, and State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.
The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China.
ACS Nano. 2025 Jul 15;19(27):24701-24712. doi: 10.1021/acsnano.4c16139. Epub 2025 Jul 3.
Cancer remains a significant global health challenge, with early and accurate detection being key to improving treatment outcomes. Developing targeted photosensitizers (PS) that selectively image and treat cancer cells is critical for cancer diagnosis, staging, and treatment monitoring. Understanding the hypoxic nature of solid tumors is essential in cancer detection, as hypoxia is associated with tumor aggressiveness and therapy resistance. Nitroreductase (NTR), which is overexpressed in hypoxic tumors, offers a target for selective imaging and treatment. In this study, we developed a type-I PS called TPAPyN, which is responsive to NTR. TPAPyN facilitates the imaging of hypoxic cancer cells and facilitates image-guided photodynamic therapy (PDT). Because of photoinduced electron transfer, TPAPyN does not emit fluorescence in the aqueous environment. However, its fluorescence is restored when NTR cleaves the nitrofuran quencher, forming highly emissive TPAPy aggregates. This characteristic makes TPAPyN a valuable fluorescent probe for specific imaging of NTR-overexpressed cancer cells. Additionally, TPAPy exhibits high efficiency in generating reactive oxygen species, indicating its potential as a PS for cancer treatment via PDT.
癌症仍然是一项重大的全球健康挑战，早期准确检测是改善治疗效果的关键。开发能够选择性地对癌细胞进行成像和治疗的靶向光敏剂（PS）对于癌症诊断、分期及治疗监测至关重要。了解实体瘤的缺氧特性在癌症检测中至关重要，因为缺氧与肿瘤侵袭性和治疗抗性相关。硝基还原酶（NTR）在缺氧肿瘤中过表达，为选择性成像和治疗提供了一个靶点。在本研究中，我们开发了一种对NTR有反应的I型PS，称为TPAPyN。TPAPyN有助于对缺氧癌细胞进行成像，并有助于图像引导的光动力疗法（PDT）。由于光诱导电子转移，TPAPyN在水性环境中不发出荧光。然而，当NTR裂解硝基呋喃猝灭剂时，其荧光恢复，形成高发射性的TPAPy聚集体。这一特性使TPAPyN成为用于NTR过表达癌细胞特异性成像的有价值的荧光探针。此外，TPAPy在产生活性氧方面表现出高效率，表明其作为通过PDT进行癌症治疗的PS的潜力。
