Ion transporters: emerging agents for anticancer therapy

Natural ion channels are pore-forming proteins that allow ions to pass through biomembranes, playing pivotal roles in almost all facets of cellular physiological functions. Biomimetic ion transporters were initially investigated for the purpose of treating lifethreatening channelopathies. Recent studies have indicated that membrane-active synthetic ionophores possess desirable anticancer bioactivity against diverse cancer cell lines by disturbing intracellular ion homeostasis, triggering oxidative stress, and inducing apoptosis in tumors. Recent progress on ionophore-related antitumor therapeutics is comprehensively summarized in this review, including the molecular design principles, functional mechanisms, and characterization methods. Finally, we conclude this review by discussing the future opportunities and challenges in this field. It is anticipated that this review will provide an existing panoramic sketch and future directions toward the construction of novel ion transporters with simplified preparation procedures, enhanced biocompatibility, and desirable anti-proliferative activities, which may further accelerate their therapeutic applications in clinical treatments.