A water-dependent reversible photoacidity strategy for cancer treatment

In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which con-tained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline com-pound (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 pro-vides a novel phototherapy strategy for cancer treatment.

Automated summary

A water-dependent reversible photoacidity (W-RPA) mechanism has been discovered, in which the proton is dissociated from water locked by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) under laser irradiation. This mechanism has been applied for cancer treatment and shows promising antitumor effects.