Shahroud University of Medical Sciences Shahroud Journal of Medical Sciences 2423-6594 12 2 2026 05 02 Nanodiamonds in Oral Cancer Therapy: A Comprehensive Narrative Review 53 72 eng Alireza Asadi Dental School, Shiraz University of Medical Sciences, Shiraz, Iran. Milad Zanjani Postgraduate Student, Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Mohammad Bahador Postgraduate student, Department of Endodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Elaheh Mohammadi Zhengzhou University, Henan, China. Yasamin Ghahramani Oral and Dental Disease Research Center, Department of Endodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. 2025 05 10 2025 10 19 Background: Oral cancer, predominantly oral squamous cell carcinoma (OSCC), remains a major global health concern characterized by late detection, aggressive progression, and limited therapeutic success. Despite advances in surgery, radiotherapy, and chemotherapy, treatment resistance and systemic toxicity continue to compromise clinical outcomes. Nanotechnology-based approaches offer new possibilities to improve drug delivery, selectivity, and treatment efficacy. This review summarizes current research on the application of nanodiamonds (NDs) in oral cancer therapy, focusing on their mechanisms of action, experimental findings, and translational potential. Methods: A critical analysis of published studies was performed, highlighting investigations on ND-based drug and gene delivery systems in both in vitro and in vivo models of oral cancer. The reviewed evidence was categorized according to major mechanistic pathways, including apoptosis induction, drug resistance modulation, and theranostic applications. Results: NDs possess a high surface area, favorable biocompatibility, and versatile surface chemistry, which enable efficient drug and gene conjugation. ND–drug complexes such as ND–doxorubicin have demonstrated enhanced cellular uptake, controlled release, and reduced cytotoxicity in preclinical settings compared with free drugs. ND-mediated gene delivery has also shown potential for suppressing oncogene expression and restoring drug sensitivity. Preliminary in vivo studies indicate good tumor-targeting ability and short-term safety. However, key challenges remain regarding large-scale synthesis, biological variability, long-term biodistribution, and regulatory classification. Conclusion: Current preclinical evidence suggests that NDs are promising nanocarriers for oral cancer therapy. Nevertheless, their translation to clinical use requires further investigation into pharmacokinetics, immunological safety, and manufacturing reproducibility. Future work should aim to optimize ND formulations and design rigorous clinical trials to establish their therapeutic value in humans. Keywords: Nanodiamonds, Oncology, Drug delivery, Squamous carcinoma, Nano biotechnology.