RESUMEN
In this article, we designed and synthesized the thionated NpImidazole derivatives BS and NS, new heavy-atom-free photosensitizers, which efficiently generate a triplet excited state with high singlet oxygen quantum yield. The introduction of the CâS bond to the NpImidazole core is essential for increasing spin-orbit coupling (SOC). The fluorescence emission of BS and NS was quenched at standard ambient temperature, accompanied with the increase in the ISC process from the singlet states to triplet excited states via thionation. BS and NS showed negligible dark cytotoxicity against HeLa cells in working concentration. In contrast, BS and NS rapidly induced cell death under blue light irradiation both under normoxia and hypoxia conditions. Our current study demonstrates that the CâS group can play an important role in type I ROS generation of PSs, which are unprecedented in the previous reports. Finally, the photophysical changes were assigned to the oxidative desulfurization of the CâS group of BS and NS to the CâO group of the corresponding BO and NO via hypochlorite. The combined results demonstrated the dual function of BS and NS as a fluorescent imaging agent for ClO- and an anti-cancer therapeutic by PDT that showed the potential strategy for "one-for-all" and multifunctional agents.
Asunto(s)
Colorantes Fluorescentes/química , Ácido Hipocloroso/análisis , Imidazoles/química , Fármacos Fotosensibilizantes/química , Tionas/química , Diseño de Fármacos , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , Células HeLa , Humanos , Imidazoles/síntesis química , Imidazoles/farmacología , Modelos Moleculares , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Imagen Óptica , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/farmacología , Tionas/síntesis química , Tionas/farmacología , Hipoxia Tumoral/efectos de los fármacosRESUMEN
Sulfur-substituted biocompatible carbonyl fluorophores have been recognized as effective heavy-atom-free photosensitizers (PSs) for cancer therapy due to their remarkable phototherapeutic properties. However, guidelines on their molecular design are still a substantial challenge. Most of the existing thiocarbonyl-based PSs are nonemissive in both the solution and restricted states, which hinders their further biomedical applications. Herein, we report the interesting finding that sulfur-substituted coumarins exhibit an uncommon phenomenon, aggregation-induced emission. More intriguingly, we also found that the introduction of a strong electron-accepting trifluoromethyl group is crucial to facilitate the mitochondrial-targeting ability of neutral coumarin fluorophores. The resulting CMS-2 PS displayed selective imaging of mitochondria and exhibited much higher photodynamic therapy efficiency toward cancer cells than that of the commercial PS erythrosine B. This work provides deep insight into the molecular design of heavy-atom-free thiobase-based PSs and simultaneously offers a great opportunity to develop novel mitochondrial-targeting fluorescent indicators with neutral bioinspired platforms.
Asunto(s)
Neoplasias , Medicina de Precisión , Neoplasias/tratamiento farmacológico , Fármacos FotosensibilizantesRESUMEN
Novel thiocarbonyl derivatives (NIS and CRNS) with excellent ROS generation abilities are synthesized and studied as potential photosensitizers for one- and two-photon excited photodynamic therapy. In particular, NIS-Me and CRNS display outstanding phototoxicity toward HeLa cells under two-photon excitation (800 nm) with negligible dark toxicity.