Anticancer drug resistance implicates multifunctional mechanisms, and
hypoxia is one of the key factors in therapeutic resistance.
Hypoxia-specific
therapy is considered an extremely effective strategy to fight against
cancer. The development of small molecule-based synthetic
anion transporters has also recently drawn attention for their potential therapeutic applications against several ion-transport-associated diseases, such as
cancer and others. Herein, we describe the development of a
hypoxia-responsive proanionophore to trigger controlled transport of
anions across membranes under pathogenic conditions. Herein, we report the development of tetraphenylethene (TPE)-based
anion transporters. The sulfonium-linked p-nitrobenzyl containing TPE-based proanionophore could be converted into a lipophilic fluorescent Cl- ion carrier in a hypoxic or reductive environment. Stimuli such as
nitroreductase (NTR) and
glutathione (GSH) mediated regeneration of the TPE-based active Cl- ion transporter also showed aggregation-induced emission (AIE) properties. We hypothesize that such
hypoxia and reductive stimuli activatable proanionophores have tremendous potential to fight against
channelopathies, including
cancer.