An AIEgen-based photosensitizer for lysosome imaging and photodynamic therapy in tumor

• Published in: Sensors and actuators. B, Chemical Chemical, 2021-05, Vol.335, p.129698, Article 129698
• Main Authors: Huang, Wendi, Zhang, Yujie, Tan, Xueying, Wang, Nan, Wang, Jinhui, He, Menglan, Peng, Jiejun, Hu, Jingbo, Zhao, Yufen, Wang, Shuanghu
• Format: Article
• Language: English
• Subjects: Aggregation-induced emission; Anticancer properties; Density functional theory; Energy gap; Fluorescence; Lysosome imaging; Medical imaging; Molecular orbitals; Morpholine; Near infrared radiation; Photodynamic therapy; Photosensitizer; Quenching; Stacking; Tumor
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2021.129698

•An AIEgen-based photosensitizer MP-TPEDCH was fabricated.•MP-TPEDCH has an excellent AIE performance, large stoke shift and broad emission wavelength up to near-infrared region.•MP-TPEDCH exhibits good photostability, high lysosome targeting specificity, and excellent ROS generation ability.•MP-TPEDCH can be used as a therapeutic agent both for lysosome imaging and photodynamic therapy. Lysosome is an indispensable organelle and its dysfunction often leads to some neurodegenerative diseases. Traditional fluorescent lysosome probes usually have conjugate structures and the π-π stacking can lead to aggregation-caused quenching (ACQ), which limits its application in bioimaging. In this work, we have designed an AIEgen-based photosensitizer MP-TPEDCH by introducing a lysosome-targeting moiety of 4-(2-chloroethyl)morpholine (MP) to a fluorescent AIE skeleton TPEDCH. The optimized structure calculated by density functional theory (DFT) reveals it has a propeller-shaped conformation, which severely inhibits the intermolecular π-π stacking interaction and therefore results in fluorescence quenching in the isolate state. Moreover, it has a broad emission wavelength up to 850 nm and exhibits typical AIE features. The electronic clouds on highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are effectively separated, suggesting MP-TPEDCH had a small singlet-triplet energy gap. Encouragingly, it has been demonstrated that MP-TPEDCH showed high photostability, excellent lysosome targeting specificity, well ROS generation ability and dramatically enhanced antitumor effect under NIR irradiation. The proposed probe not only expands the family of lysosome imaging agents but also provides a new strategy for preparing effective photosensitizers in cancer treatment.