A Doubly Caged Bis(salicylamide)-Based Anion Transporter for Phototriggered Breast Cancer Therapy

Formulation of ion transporters, which hold great potential for anticancer therapy, as prodrugs/protransporters can overcome their nontarget activity, allowing for local activation using specified stimuli. Photocleavable protecting groups offer a robust strategy for caging transporter activity. Their reliance on light as a stimulus ensures ease of application and precise spatiotemporal control. Thus, there is a need to develop protransporters that are activatable in the biologically benign visible region of the electromagnetic spectrum. Herein, we report a series of bis-(salicylamide)-based anion antiporters caged with o-nitrobenzyl groups to create protransporters that can be activated by 405 nm light. Active transporter release via two-step photocleavage and the subsequent photoinduced recovery of ion transport activity was verified. In vitro photoactivation of protransporters using 405 nm light efficiently induced cell death in MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines.