1.D.297.  The Artificial G-Quadruplex-based K⁺ Channel (GQ-KC) Family  

G-quadruplex-based artificial transmembrane K⁺ channels induce cancer cell apoptosis by perturbing potassium ion homeostasis (Liu et al. 2024), and these have been developed to facilitate intracellular K⁺ efflux, which perturbs the cellular ion homeostasis, thereby inducing cancer cell apoptosis. Cholesterol-tag, a lipophilic anchor moiety, serves as a rudiment for the G-quadruplex immobilization onto the membrane, while G-quadruplex channel structure as a transport module permits ion binding and migration along the channels. A c-Myc sequence tagged with two-cholesterol is designed as a representative lipophilic G-quadruplex, which forms intramolecular parallel G-quadruplex with three stacks of G-quartets (Ch₂-Para3). Fluorescence transport assays demonstrate Ch₂-Para3 a high transport activity (EC₅₀ = 10.9 × 10^-6 m) and an ion selectivity (K⁺/Na⁺ selectivity ratio of 84). Ch₂-Para3 mediated K⁺ efflux in cancer cells is revealed to purge cancer cells through K⁺ efflux-mediated cell apoptosis, which is confirmed by monitoring the changes in membrane potential of mitochondria, leakage of cytochrome c, reactive oxygen species yield, as well as activation of a family of caspases. The lipophilic G-quadruplex exhibits obvious antitumor activity in vivo without systemic toxicity. Thus, a functional scheme aimed at generating DNA-based selective artificial membrane channels for the purpose of regulating cellular processes and inducing cell apoptosis, which shows promise for anticancer therapy in the future (Liu et al. 2024).  

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