From recognition to delivery: nucleic acid aptamers in miRNA-related diagnosis and therapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the most common primary malignant liver tumour, remains a major clinical challenge because of its low early diagnosis rate and high post-treatment recurrence. MicroRNAs (miRNAs) play key regulatory roles in HCC development and progression and are potential liquid biopsy biomarkers and therapeutic targets. However, the low abundance and instability of miRNAs in body fluids, together with the limitations of conventional detection methods, have hindered their clinical translation. Nucleic acid aptamers, owing to their high affinity, specificity, and ease of chemical modification, are valuable in miRNA-related detection and targeted delivery. This narrative review summarises technical strategies for aptamer-based and aptamer-inspired detection of HCC-associated miRNAs, as well as aptamer-guided miRNA delivery systems in HCC therapy. Importantly, most aptamers used in HCC research do not directly bind miRNAs; instead, they target HCC cells, surface proteins, or exosomes, whereas miRNAs serve as detection analytes or therapeutic cargo. It analyses the design logic and potential integration pathways of “recognition-delivery” platforms, while distinguishing conceptual integration from experimentally validated single-platform systems. Challenges and future directions are also discussed.