Innovative Applications of Nucleic Acid Aptamers in Colorectal Cancer Diagnosis and Therapy: From Selection Optimization to Clinical Translation.

Colorectal cancer (CRC), a gastrointestinal malignancy with persistently high global incidence and mortality rates, urgently demands more efficient early screening strategies and precision therapeutic approaches. Nucleic acid aptamers, recognized as "chemical antibodies", have emerged as a research hotspot in CRC diagnosis and treatment due to their high target specificity, flexible chemical modifiability, and cost-effective synthesis. In diagnostic applications, integrating aptamers with fluorescence, surface-enhanced Raman scattering (SERS), and electrochemical biosensors, along with functionalized nanomaterials such as quantum dots, gold nanoparticles, and graphene, has enabled ultrasensitive detection of biomarkers including carcinoembryonic antigen (CEA), miRNAs, exosomes, and circulating tumor cells (CTCs). In the therapeutic arena, we highlight aptamer-decorated lipidic, polymeric, and inorganic nanocarrier systems for targeted drug delivery featuring pH/glutathione (GSH)-responsive release mechanisms, and we review emerging immunotherapeutic regimens that employ PD-1/PD-L1 blocking aptamers alone or in combination with immunomodulatory agents or small activating RNAs. Finally, current challenges in aptamer applications-such as in vivo stability, targeted delivery efficiency, large-scale production, and clinical translation-are critically discussed. Future perspectives propose AI-assisted intelligent aptamer design, multi-omics-integrated diagnostic and therapeutic platforms, and standardized clinical trials to advance the implementation of nucleic acid aptamers in CRC precision medicine.