Targeting oral cancer with MicroRNA-based therapeutics: The role of tumor-suppressor miRNAs and exosome delivery.

[OBJECTIVE] To evaluate the potential of tumor-suppressor microRNAs delivered via exosomes, especially those from human dental pulp stem cells, as a targeted therapy for oral cancer and to examine recent strategies that improve their delivery and clinical application. Although extensive preclinical evidence supports the anticancer functions of TS-miRNAs, the robustness and reproducibility of their effects vary substantially across experimental models. Exosome-based delivery has emerged as a biologically attractive strategy to improve miRNA stability, targeting specificity, and therapeutic efficacy.

[DESIGN] This review examines preclinical and translational studies on the delivery of tumor-suppressor microRNAs using exosomes, focusing on human dental pulp stem cell derived exosomes and recent strategies that enhance their targeting and therapeutic effectiveness. Relevant studies were identified through PubMed, Scopus, Web of Science, and Google Scholar.

[RESULTS] Studies show that using exosomes to deliver tumor-suppressor microRNAs can make them more stable, help them enter cells more efficiently, and reach tumors more effectively. Among multiple clinically relevant sources, including bone marrow and adipose-derived mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and tumor-derived vesicles, human dental pulp stem cell (hDPSC)-derived exosomes represent a promising, though not yet potential advantages suggested by preclinical studies. Exosomes from human dental pulp stem cells are especially promising, as they are highly compatible with the body and naturally target cancer cells better than other above sources. Engineering these exosomes can further improve their precision and reduce unwanted effects. However, challenges like producing them on a large scale, maintaining consistency, and applying them in real-world clinical settings still remain.

[CONCLUSION] Exosome-mediated delivery of tumor-suppressor miRNAs offers an exciting and promising direction in oral cancer therapy. By combining the regulatory power of miRNAs with the natural delivery capacity of exosomes, this strategy could open new possibilities for safer, more effective, and personalized treatment of oral cancer. This review critically evaluates mechanistic evidence, compares exosome sources, and outlines realistic translational barriers, avoiding overstatement of near-term clinical applicability.