Molecular engineering to red-shift the absorption band of AIE photosensitizers and improve their ROS generation ability

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2023-04, Vol.11 (14), p.3252-3261
• Main Authors: Zhang, Yuhui, Pan, Xiaohong, Shi, Haixing, Wang, Yaqi, Liu, Wenzhen, Cai, Liangzhi, Wang, Le, Wang, Huanhuan, Chen, Zhuo
• Format: Article
• Language: English
• Subjects: Absorption; Absorption spectra; Agglomeration; Animals; Conjugation; Doppler effect; Emission; Engineering; Fluorescence; Irradiation; Mice; Mice, Inbred BALB C; Oxygen; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - pharmacology; Radiation; Reactive Oxygen Species; Red shift; Singlet Oxygen
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d2tb02829h

Photodynamic therapy (PDT) with aggregation-induced emission photosensitizers (AIE-PSs) has attracted increasing attention for their enhanced fluorescence and reactive oxygen species (ROS) generation abilities upon aggregation. However, it is difficult for AIE-PSs to simultaneously achieve long-wavelength excitation (>600 nm) and high singlet oxygen quantum yield, which restricts their application in deep-tissue PDT. In this study, four novel AIE-PSs were developed by appropriate molecular engineering, and their absorption peaks shifted from 478 to 540 nm with a tail extending to 700 nm. Meanwhile, their emission peaks were also moved from 697 nm to 779 nm with a tail extending over 950 nm. Importantly, their singlet oxygen quantum yields successfully increased from 0.61 to 0.89. Moreover, TBQ, the best photosensitizer developed by us, has been successfully applied to image-guided PDT in BALB/C mice bearing 4T1 breast cancer under red light (605 ± 5 nm) irradiation, with IC50 less than 2.5 μM at a low light dose (10.8 J cm −2 ). The success of this molecular engineering indicates that increasing the number of acceptors is more effective at red-shifting the absorption band of AIE-PSs than increasing the number of donors, and extending the π-conjugation of acceptors will red-shift the absorption-emission band, increase the maximum molar extinction coefficient, and improve the ROS generation ability of AIE-PSs, thus providing a new strategy for the design of advanced AIE-PSs for deep-tissue PDT. Increasing the number of acceptors and extending their π-conjugation will red-shift the absorption-emission band, increase the maximum molar extinction coefficient, and improve the ROS generation ability of AIE-photosensitizers.