DNALogic Gate-Triggered Membrane Fusion for AccuratelyDetecting and Killing Cancer Cells

Accurately and sensitively identifying and killing cancer cells, especially those in deep tissues, is of paramount importance but presents significant challenges. Herein, a membrane protein and adenosine triphosphate (ATP)-driven DNA logic gate-modified liposome is designed to coat zinc peroxide (ZP) nanoparticles integrated with nanozymes (ZP/RuTe@L/DNA) to accurately identify and induce cell apoptosis in cancer cells through a reactive oxygen species (ROS)-mediated mechanism under acid conditions in cancer cells. In this system, DNA logic gate-functionalized liposomes are loaded with ZP and nanozymes, while HeLa cancer cells are functionalized with a DNA segment that is complementary to a segment of the DNA logic gate. For the DNA logic gate, a DNA aptamer was employed for membrane protein recognition, and another aptamer was used for the response of extracellular ATP. Activation of the DNA logic gate occurs only when both biomarkers are simultaneously present. Once activated, the DNA logic gate-modified liposome could hybridize with DNA segment-modified HeLa cells, leading to liposome–HeLa cell fusion and the release of ZP/RuTe into HeLa cells. Under acid conditions, ZP could decompose to release H₂O₂ and Zn²⁺, which could promote the production of •O₂^– and H₂O₂ by inhibiting the electron transport chain. Concurrently, the released RuTe exhibits glutathione (GSH) depletion and peroxidase (POD) and nicotinamide adenine dinucleotide (NADH) peroxidase-like activities, generating highly toxic hydroxyl radical (•OH), disrupting the cellular redox homeostasis, and inducing cell apoptosis. The ZP/RuTe@L/DNA system could not only accurately detect cancer cells in complex cell mixtures but also present a novel method for liposome–membrane fusion processes in drug delivery. This study presents significant potential for application in precise cancer diagnosis and therapy.