Chen Dapeng, Shao Jinjun, Zhang Tian, Xu Kang, Liang Chen, Cai Yu, Guo Yuxin, Chen Peng, Mou Xiao-Zhou, Dong Xiaochen
Key Laboratory of Flexible Electronics (KLOFE) and School of Flexible Electronics (Future Technologies), Nanjing Tech University, Nanjing 211816, China.
Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China.
Nano Lett. 2024 Jun 10. doi: 10.1021/acs.nanolett.4c01862.
The quantum yield of reactive oxygen species is of central importance for the development of organic photosensitizers and photodynamic therapy (PDT). A common molecular design approach for optimizing organic photosensitizers involves the incorporation of heavy atoms into their backbones. However, this raises concerns regarding heightened dark cytotoxicity and a shortened triplet-state lifetime. Herein, we demonstrate a heavy-atom-free (HAF) photosensitizer design strategy founded on the singlet fission (SF) mechanism for cancer PDT. Through the "single-atom surgery" approach to deleting oxygen atoms in pyrazino[2,3-]quinoxaline skeleton photosensitizers, photosensitizers PhPQ and TriPhPQ are produced with Huckel's aromaticity and Baird's aromaticity in the ground state and triplet state, respectively, enabling the generation of two triplet excitons through SF. The SF process endows photosensitizer PhPQ with an ultrahigh triplet-state quantum yield (186%) and an outstanding O quantum yield (177%). Notably, HAF photosensitizers PhPQ and TriPhPQ enhanced PDT efficacy and potentiated αPD-L1 immune check blockade therapy , which show their promise for translational oncology treatment.
活性氧物质的量子产率对于有机光敏剂的开发和光动力疗法（PDT）至关重要。优化有机光敏剂的一种常见分子设计方法是在其主链中引入重原子。然而，这引发了对暗细胞毒性增加和三重态寿命缩短的担忧。在此，我们展示了一种基于单重态裂变（SF）机制的无重原子（HAF）光敏剂设计策略，用于癌症光动力疗法。通过“单原子手术”方法删除吡嗪并[2,3 - ]喹喔啉骨架光敏剂中的氧原子，分别制备出在基态和三重态具有休克尔芳香性和贝尔德芳香性的光敏剂PhPQ和TriPhPQ，从而能够通过单重态裂变产生两个三重态激子。单重态裂变过程赋予光敏剂PhPQ超高的三重态量子产率（186%）和出色的O量子产率（177%）。值得注意的是，无重原子光敏剂PhPQ和TriPhPQ提高了光动力疗法的疗效，并增强了αPD - L1免疫检查点阻断疗法，这表明它们在转化肿瘤学治疗方面具有前景。
