DNA Logic-Gated Biosensing of the Tumor Microenvironment for Multicomponent Profiling and Programmable Molecular Decision-Making

The tumor microenvironment (TME) is spatially and temporally heterogeneous, limiting the specificity of single-biomarker strategies for resolving complex tumor states. The sequence programmability and predictable base pairing of DNA allow multiple biological inputs to be recognized, logically processed, and translated into defined analytical outputs. Here, we review recent advances in DNA logic-gated biosensors and associated nanodevices for multicomponent TME profiling, spanning nucleic acids, proteins, extracellular vesicles, and physicochemical cues. Particular attention is directed to how molecular recognition, Boolean computation, signal amplification, and transduction collectively govern analytical specificity, signal-to-noise ratio, reaction kinetics, and operational reliability in complex biological matrices. We further compare chemical stabilization, smart delivery, and spatial confinement strategies, together with applications in tumor phenotyping, immune-response monitoring, molecular imaging, and conditional therapeutic activation. Emerging directions include continuous and wearable monitoring, spatially organized molecular circuits, and advanced DNA molecular computing. Translation, however, will require improved nuclease resistance, delivery efficiency, threshold robustness, fabrication reproducibility, clinical-matrix validation, and system-level integration. By converting multicomponent TME signals into programmable molecular decisions, DNA logic-gated biosensing may support more reliable tumor characterization, precision diagnosis, and context-dependent therapy.