Leveraging DNA‐Encoded Cell‐Mimics for Environment‐Adaptive Transmembrane Channel Release‐Induced Cell Death

Abstract The advancement of cell‐mimic materials, which can forge sophisticated physicochemical dialogues with living cells, has unlocked a realm of intriguing prospects within the fields of synthetic biology and biomedical engineering. Inspired by the evolutionarily acquired ability of T lymphocytes to release perforin and generate transmembrane channels on targeted cells for killing, herein we present a pioneering DNA‐encoded artificial T cell mimic model (ARTC) that accurately mimics T‐cell‐like behavior. ARTC responds to acidic conditions similar to those found in the tumor microenvironment and then selectively releases a G‐rich DNA strand (LG4) embedded with C12 lipid and cholesterol molecules. Once released, LG4 effectively integrates into the membranes of neighboring live cells, behaving as an artificial transmembrane channel that selectively transports K + ions and disrupts cellular homeostasis, ultimately inducing apoptosis. We hope that the emergence of ARTC will usher in new perspectives for revolutionizing future disease treatment and catalyzing the development of advanced biomedical technologies.