An “all-in-one” strategy based on the organic molecule DCN-4CQA for effective NIR-fluorescence-imaging-guided dual phototherapy

Dual phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) is considered to be a more effective therapeutic method against cancer than single treatment. Therefore, the development of a single material with both near-infrared (NIR)-laser-triggered PDT and PTT abilities is highly desirable but remains a great challenge. A design philosophy for photosensitizers for integrated PDT and PTT treatment has been put forward: (1) a high molar extinction coefficient in the NIR region; (2) suitable LUMO and T1 energy levels to regulate intersystem crossing for effective singlet oxygen (1O2) generation for PDT; and (3) the suppression of fluorescence emission to enhance the process of nonradiative transition with appropriate chemical modifications. Herein, an "all-in-one" functional material, di-cyan substituted 5,12-dibutylquinacridone (DCN-4CQA), for diagnosis and therapy was obtained. DCN-4CQA possesses dual-functional phototherapeutic activity and NIR fluorescence and it was produced via a facile synthesis process from the classic organic photoelectric material quinacridone. We then prepared smart water-soluble nanoparticles (NPs), DCN-4CQA/F127, using Pluronic® 127 (F127) as a drug carrier. The NPs exhibited excellent biocompatibility, robust photostability, NIR fluorescence, a high photothermal conversion efficiency (η = 47.3%), and sufficient 1O2 generation (ΦΔ = 24.3%) under NIR laser irradiation. Remarkably, the DCN-4CQA/F127 NPs significantly inhibited tumor growth in mice subjected to NIR laser irradiation. This study provides a new route for the development of highly efficient, low-cytotoxicity photosensitizers for fluorescence-imaging-guided PTT/PDT.