Time-dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE-active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Abstract

Pathogen infection and cancer are the two major human wealth and health problems. Fluorescence-guided photodynamic therapy (FL-PDT) emerged as a hotspot in antibacterial and anticancer treatment with prominent merits including noninvasiveness, no drug resistance, real-time monitoring, spatiotemporal precision and synergistic effect over conventional therapeutic modalities. In this work, we achieved successfully an organic salt photosensitizer (PS), called 4TPA-BQ with aggregation-induced emission feature via one-step reaction. Owing to its aggregation-induced reactive oxygen species generation effect and sufficient small energy gap between the singlet and triplet states, 4TPA-BQ shows a satisfactorily high 1 O2 generation efficiency of 98.7%. Unprecedentedly, by regulating the external conditions, time-dependent, specific and controllable targeting via FL-PDT was realized for the first time. Both in vitro and in vivo experiments confirmed that 4TPA-BQ exhibited potent photodynamic antibacterial performance even against ampicillin-resistant Escherichia coli with good biocompatibility in a short time (15 min), indicating that 4TPA-BQ holds promising potential for combating multiple pathogen bacteria. When the incubation time persisted long enough to 12 h, cancer cells were ablated efficiently while the normal cells were essentially unaffected. This is the first attempt to explore a novel time-dependent PDT with the aid of one individual PS for bacterial elimination and cancer cell ablation, which not only update the design principle of efficient PSs, but also stimulates FL-PDT development for potential clinical applications. ASSOCIATED CONTENTSupporting Information. Materials and methods, synthetic procedures, characterization, crystallographic data and computational details, including Figures S1−S20 and Tables S1-S2. (PDF). This material is available free of charge via the Internet at