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An Activatable Heavy-Atom-Free Upconversion Photosensitizer for Targeted Imaging and Treatment of Tumors
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-12-05 , DOI: 10.1021/acs.jmedchem.4c02679
Chao Zhao, Wanlu Sun, Yanyan Zhu, Xiaoyan Huang, Ye Sun, Hai-Yan Wang, Yi Pan, Yi Liu

Photodynamic therapy (PDT) is an innovative and promising method for treating tumors that has attracted significant interest but still faces several challenges, such as a lack of selectivity, deep penetration of light, and efficient ROS generation. To address these challenges, we optimized and synthesized a series of photosensitizers and successfully developed a heavy-atom-free near-infrared FUCL photosensitizer NFh-NMe-2. This photosensitizer can generate singlet oxygen (1O2) and induce cellular apoptosis under 808 nm light. For the safe ablation of microtumors in vivo, an activatable FUCL photosensitizer NFh-NTR was developed based on the overexpression of nitroreductase (NTR). NFh-NTR could be activated by NTR, leading to the release of the photosensitizer NFh-NMe-2, restoring the fluorescence signal, and effectively killing tumor cells under 808 nm light irradiation. This work opens new possibilities in the chemical design of an FUCL photosensitizer for cancer treatment.

中文翻译:


一种可激活的无重原子上转换光敏剂,用于肿瘤的靶向成像和治疗



光动力疗法 (PDT) 是一种治疗肿瘤的创新且有前途的方法,引起了人们的极大兴趣,但仍面临一些挑战,例如缺乏选择性、光的深度渗透和高效的 ROS 生成。为了应对这些挑战,我们优化合成了一系列光敏剂,并成功开发了无重原子的近红外 FUCL 光敏剂 NFh-NMe-2。这种光敏剂可以在 808 nm 光下产生单线态氧 (1O2) 并诱导细胞凋亡。为了在体内安全消融微肿瘤,基于硝基还原酶 (NTR) 的过表达开发了一种可激活的 FUCL 光敏剂 NFh-NTR。NFh-NTR 可被 NTR 激活,导致光敏剂 NFh-NMe-2 的释放,恢复荧光信号,并在 808 nm 光照射下有效杀死肿瘤细胞。这项工作为用于癌症治疗的 FUCL 光敏剂的化学设计开辟了新的可能性。
更新日期:2024-12-05
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