A water-dependent reversible photoacidity strategy for cancer treatment
Abstract—In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which contained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) has been found, in which the proton is not dissociated from TQs-Th-PEG5 itself but from a water locked by TQs-Th-PEG5 under the irradiation of a 660 nm laser. After turning off the laser, the produced acid will disappear quickly. This process is repeatable with no consumption of TQs-Th-PEG5. More importantly, water is indispensable. Furthermore, it is confirmed that there is no other element involved in the process except TQs-Th-PEG5, light and water. Excitingly, W-RPA therapy mediated by TQs-Th-PEG5 nanoparticle exhibits remarkable antitumor effect both in vitro and in vivo, especially in hypoxic tumors with diameter larger than 10 mm owing to its oxygen-independent feature. This study not only discovers a W-RPA mechanism but also provides a novel phototherapy strategy for cancer treatment.