Design of near-infrared aggregation-induced emission photosensitizers by rr-bridge engineering for boosting theranostic efficacy

Fluorescence imaging-guided photodynamic therapy holds great promise for application in precise cancer diagnosis and treatment, which has motivated high requirements for phototheranostic agents. However, current photosensitizers (PSs) generally face limitations such as short emission wavelength and inadequate reactive oxygen species (ROS) production. Aggregation-caused quenching issue also hinders the phototheranostic efficiency of PSs. Herein, the rr-bridge modulation strategy is proposed to construct ionic PSs with enhanced bioimaging and therapeutic outcomes. Two donor- rr-acceptor (D- rr-A) molecules TPCPY and TFCPY were obtained by incorporating phenyl and furan units as rr-bridge, respectively. Both PSs feature aggregation-induced near-infrared emission. Under light irradiation, TPCPY and TFCPY can produce both type I and II ROS. Introducing furan ring in TFCPY enhances the ROS generation capacity by type I photosensitization process, which is consistent with the reduced energy gap between singlet and triplet states from theoretical calculation. Furthermore, TFCPY can achieve quick cellular uptake, accumulate in mitochondria, and then efficiently kill cancer cells, which is superior to TPCPY . Consequently, TFCPY exhibited good antitumor outcomes and excellent in vivo fluorescence imaging ability. This work provides an efficient molecular engineering of introducing heterocycles into the D- rr-A skeleton to develop high-performance PSs with both type I and II ROS generation. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.