Fluorogenic RNA aptamers in cancer: emerging platforms for molecular imaging, biosensing, and precision oncology

Fluorogenic RNA aptamers have emerged as powerful molecular tools for cancer imaging, biosensing, and biomarker detection due to their high specificity, low background fluorescence, and genetic encodability. These short RNA molecules activate fluorescence upon binding specific fluorogens, enabling real-time visualization of intracellular targets and dynamic molecular processes in living systems. Recent advances in RNA structural engineering, fluorophore optimization, and biosensor integration have significantly expanded the translational applications of fluorogenic aptamers in oncology. This mini-review summarizes the structural principles, fluorescence activation mechanisms, and cancer-related applications of fluorogenic RNA aptamers and related nucleic acid biosensors. Foundational studies describing the architecture of fluorogenic aptamer families, including Spinach, Broccoli, Mango, Pepper, Squash, and Beetroot, are discussed with emphasis on G-quadruplex-mediated fluorogen stabilization and fluorescence enhancement. Furthermore, recent developments in CRISPR/Cas-assisted fluorogenic biosensors, dual-color RNA imaging systems, fluorogenic DNAzymes, and amplification-driven aptamer platforms are highlighted. Direct applications across multiple malignancies, including brain, breast, colorectal, liver, lung, prostate, and skin cancers, demonstrate the growing utility of these technologies for tumor-associated RNA detection, epigenetic biomarker analysis, molecular imaging, and therapeutic monitoring. In addition, advances in fluorescence brightness, structural stability, and multiplex imaging strategies have improved the sensitivity and adaptability of fluorogenic RNA systems for complex biological environments. Despite current limitations related to RNA stability, intracellular delivery, and tissue penetration, fluorogenic RNA aptamers represent highly promising tools for next-generation precision oncology. Continued integration with nanotechnology, live-cell imaging, artificial intelligence, and molecular diagnostics is expected to enhance further their clinical and translational potential in cancer research and personalized medicine.