Abstract
Artificial ion channels have shown great potential applications in tumor treatment by disrupting ion homeostasis across cancer cell membranes. Herein, we report a de novo-designed ion channel delivery system (ICDS) based on light-sensitive nanocapsules that can induce cell apoptosis via interfering with ion homeostasis of subcellular membranes of tumors. The nanocapsules were self-assembled by the host-guest complex of azobenzene-modified quinoline helix (an artificial proton channel) and α-cyclodextrin, which can easily enter tumor cells by an endocytic effect and release proton channels under ultraviolet (UV) light irradiation. The artificial proton channels further neutralize the acidic organelles (such as lysosomes), deplete the mitochondrial membrane potential, elevate reactive oxygen species (ROS) levels, and eventually induce the apoptosis of cancer cells. As far as we know, this is the first example of an ion-interference antitumor strategy by an ion channel delivery system that may offer novel therapeutic directions for artificial ion channels.