Nanotechnology-driven diagnostics and therapeutics in oral squamous cell carcinoma: Emerging technologies, clinical translation and future perspectives
Paper Details
Nanotechnology-driven diagnostics and therapeutics in oral squamous cell carcinoma: Emerging technologies, clinical translation and future perspectives
Abstract
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and remains associated with high morbidity and mortality owing to delayed diagnosis, tumor heterogeneity, therapeutic resistance, recurrence, and treatment-related toxicity. These challenges necessitate innovative approaches for early detection and precision treatment. This narrative review critically examines recent advances in nanotechnology-driven diagnostics and therapeutics for OSCC, emphasizing their translational potential, current limitations, and future prospects. Recent peer-reviewed studies published primarily between 2020 and 2026 were critically synthesized to evaluate the biological basis of OSCC and the applications of nanotechnology in molecular diagnostics, targeted drug delivery, theranostics, immunotherapy, artificial intelligence, precision medicine, clinical translation, and safety. Rather than providing a descriptive overview, this review integrates current evidence to identify emerging trends, unresolved controversies, and key knowledge gaps. Nanotechnology has progressed from conventional drug delivery to multifunctional platforms integrating biosensing, molecular imaging, liquid biopsy, controlled drug release, targeted therapeutics, and theranostics. Integration with artificial intelligence, multi-omics, spatial biology, and gene-editing technologies has further advanced personalized diagnosis and treatment while improving therapeutic precision and reducing systemic toxicity. Although significant progress has been achieved, widespread clinical translation remains constrained by biological heterogeneity, inconsistent nanoparticle biodistribution, manufacturing and regulatory challenges, long-term safety concerns, and limited high-quality clinical validation. Future advances will depend on standardized methodologies, biomarker-guided patient stratification, multidisciplinary collaboration, and harmonized regulatory frameworks. Collectively, these developments position precision nanomedicine as a promising strategy for improving the diagnosis, treatment, and long-term management of OSCC.
Alkan A, Kılıç M, Özdemir A, Demir M. 2026. Artificial intelligence-assisted diagnosis of oral squamous cell carcinoma: Current progress, challenges and future perspectives. Oral Oncology 146, 106682.
Argelaguet R, Arnol D, Bredikhin D, Deloro Y, Velten B, Marioni JC, Stegle O. 2021. MOFA+: A statistical framework for comprehensive integration of multi-modal single-cell data. Genome Biology 21, Article 111. https://doi.org/10.1186/s13059-020-02015-1
Ariji Y, Kise Y, Fukuda M, Katsumata A, Fujita H, Ariji E. 2024. Artificial intelligence applications in oral and maxillofacial radiology and oral cancer diagnosis: Current progress and future perspectives. Dentomaxillofacial Radiology 53(2), Article 20230291. https://doi.org/10.1259/dmfr.20230291
Awawdeh M, Al-Khalili M, Al-Qudah M, Al-Ebbini D, Abu-Shaqra M. 2023. Cyclin D1 expression and its clinicopathological significance in oral squamous cell carcinoma: A systematic review. Oral Diseases 29(8), 3128–3141.
Baethge C, Goldbeck-Wood S, Mertens S. 2019. SANRA- a scale for the quality assessment of narrative review articles. Research Integrity and Peer Review 4, 5.
Blanco E, Shen H, Ferrari M. 2015. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology 33(9), 941–951. https://doi.org/10.1038/nbt.3330
Bramer WM, Rethlefsen ML, Kleijnen J, Franco OH. 2018. Optimal database combinations for literature searches in systematic reviews: A prospective exploratory study. Systematic Reviews 7, 245.
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, Psyrri A, Baste N, Neupane P, Bratland Å, 2019. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-048): A randomised, open-label, phase 3 study. The Lancet 394(10212), 1915–1928. https://doi.org/10.1016/S0140-6736(19)32591-7
Campanella G, Hanna MG, Geneslaw L, Miraflor A, Silva VWK, Busam KJ, Brogi E, Reuter VE, Klimstra DS, Fuchs TJ. 2019. Clinical-grade computational pathology using weakly supervised deep learning on whole-slide images. Nature Medicine 25(8), 1301–1309. https://doi.org/10.1038/s41591-019-0508-1
Cao M, Shi E, Wang H, Mao L, Wu Q, Li X, 2022. Personalized targeted therapeutic strategies against oral squamous cell carcinoma: An evidence-based review of the literature. International Journal of Nanomedicine 17, 4293–4306.
Chaudhary AA, Fareed M, Khan SUD, Alneghery LM, Aslam M, Alex A, 2024. Exploring the therapeutic potential of lipid-based nanoparticles in the management of oral squamous cell carcinoma. Exploration of Targeted Anti-tumor Therapy 5(6), 1223–1246.
Chaudhary S, Sharma P, Kumar V, Singh R. 2024. Nanotechnology-based therapeutic strategies for oral squamous cell carcinoma: Recent advances and future perspectives. Journal of Drug Delivery Science and Technology 95, 105670.
Coletta RD, Brennan PA, Gómez RS, Ribeiro-Silva A. 2024. Oral squamous cell carcinoma: Current concepts in biology, diagnosis and precision management. BDJ Open 10, Article 17.
Esteva A, Robicquet A, Ramsundar B, Kuleshov V, DePristo M, Chou K, Cui C, Corrado GS, Thrun S, Dean J. 2019. A guide to deep learning in healthcare. Nature Medicine 25(1), 24–29. https://doi.org/10.1038/s41591-018-0316-z
European Medicines Agency (EMA). 2021. Reflection Paper on Nanotechnology-Based Medicinal Products for Human Use. Amsterdam: European Medicines Agency.
Fadeel B, Farcal L, Hardy B, Vázquez-Campos S, Hristozov D, Marcomini A, Lynch I, Valsami-Jones E, Alenius H, Savolainen K, 2021. Advanced tools for the safety assessment of nanomaterials. Nature Nanotechnology 16(9), 951–964. https://doi.org/10.1038/s41565-021-00949-3
Falagas ME, Pitsouni EI, Malietzis GA, Pappas G. 2008. Comparison of PubMed, Scopus, Web of Science, and Google Scholar: Strengths and weaknesses. FASEB Journal 22(2), 338–342.
Fatima A, Ahmed S, Rahman MA, 2024. Global epidemiology and emerging risk factors of oral squamous cell carcinoma: An updated review. Cancers 16, Article 1042.
Ferrari R. 2015. Writing narrative style literature reviews. Medical Writing 24(4), 230–235.
Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, 2016. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. New England Journal of Medicine 375(19), 1856–1867. https://doi.org/10.1056/NEJMoa1602252
Food and Drug Administration (FDA). 2022. Drug Products, Including Biological Products, That Contain Nanomaterials: Guidance for Industry. Silver Spring, MD: U.S. Food and Drug Administration.
Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, Seitzer J, O’Connell D, Walsh KR, Wood K, 2021. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. New England Journal of Medicine 385(6), 493–502. https://doi.org/10.1056/NEJMoa2107454
Grant MJ, Booth A. 2009. A typology of reviews: An analysis of 14 review types and associated methodologies. Health Information & Libraries Journal 26(2), 91–108.
He Y, Zhang L, Wang X, et al. 2025. Advances in molecular diagnosis and precision management of oral squamous cell carcinoma. Journal of Translational Medicine 23, Article 148.
Herrada Céspedes A, Reyes M, Morales JO. 2025. Advanced drug delivery systems for oral squamous cell carcinoma: A comprehensive review of nanotechnology-based and other innovative approaches. Frontiers in Drug Delivery 5, 1596964. https://doi.org/10.3389/fddev.2025.1596964
Hosny A, Parmar C, Quackenbush J, Schwartz LH, Aerts HJWL. 2018. Artificial intelligence in radiology. Nature Reviews Cancer 18(8), 500–510. https://doi.org/10.1038/s41568-018-0016-5
Hsu PC, Lin YC, Chen CY, 2025. Early molecular diagnosis and comprehensive treatment strategies for oral squamous cell carcinoma. Current Issues in Molecular Biology 47(6), 452.
International Organization for Standardization (ISO). 2023. Nanotechnologies-Vocabulary and Guidance for Nanomaterial Characterization. Geneva: International Organization for Standardization.
Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. 2020. Head and neck squamous cell carcinoma. Nature Reviews Disease Primers 6, Article 92. https://doi.org/10.1038/s41572-020-00224-3
Kalluri R, LeBleu VS. 2020. The biology, function, and biomedical applications of exosomes. Science 367(6478), eaau6977. https://doi.org/10.1126/science.aau6977
Kelly CJ, Karthikesalingam A, Suleyman M, Corrado G, King D. 2019. Key challenges for delivering clinical impact with artificial intelligence. BMC Medicine 17, Article 195. https://doi.org/10.1186/s12916-019-1426-2
Kumar V. 2025. A comprehensive review of risk factors, diagnosis, and treatment options for oral squamous cell carcinoma. Current Cancer Therapy Reviews 21, 1–8.
Lambin P, Leijenaar RTH, Deist TM, Peerlings J, de Jong EEC, van Timmeren J, Sanduleanu S, Larue RTHM, Even AJG, Jochems A, 2017. Radiomics: The bridge between medical imaging and personalized medicine. Nature Reviews Clinical Oncology 14(12), 749–762. https://doi.org/10.1038/nrclinonc.2017.141
Li HX, Gong YW, Yan PJ, Xu Y, Qin G, Wen WP, Teng FY. 2024. Revolutionizing head and neck squamous cell carcinoma treatment with nanomedicine in the era of immunotherapy. Frontiers in Immunology 15, Article 1453753. https://doi.org/10.3389/fimmu.2024.1453753
Li J, Jiang Q, Qiu D, Chang R, Huang J, Xu Q, Wang K. 2025. A self-cycling and self-verifying electrochemical and colorimetric dual-modal biosensor for oral squamous cell carcinoma saliva detection. Biosensors and Bioelectronics 290, Article 118000. https://doi.org/10.1016/j.bios.2025.118000
Lin SH, Lin CW, Lu JW, Yang WE, Lin YM, Lu HJ, Yang SF. 2022. Cytoplasmic IGF2BP2 protein expression in human patients with oral squamous cell carcinoma: Prognostic and clinical implications. International Journal of Medical Sciences 19(7), 1198–1204. https://doi.org/10.7150/ijms.74751
Liu L, Zhong X, Zhong Y, Li L, et al. 2025. Recent advances in biomarker detection of oral squamous cell carcinoma. Frontiers in Oncology, 15.
Longo SK, Guo MG, Ji AL, Khavari PA. 2021. Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics. Nature Reviews Genetics 22(10), 627–644. https://doi.org/10.1038/s41576-021-00370-8
Maynard A, McCoach CE, Rotow JK, Harris L, Haderk F, Kerr DL, Yu EA, Schenk EL, Tan W, Zee A, 2020. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell 182(5), 1232–1251.
Monopoli MP, Åberg C, Salvati A, Dawson KA. 2012. Biomolecular coronas provide the biological identity of nanosized materials. Nature Nanotechnology 7(12), 779–786. https://doi.org/10.1038/nnano.2012.207
Mura S, Nicolas J, Couvreur P. 2013. Stimuli-responsive nanocarriers for drug delivery. Nature Materials 12(11), 991–1003. https://doi.org/10.1038/nmat3776
Mura S, Nicolas J, Couvreur P. 2013. Stimuli-responsive nanocarriers for drug delivery. Nature Materials 12(11), 991–1003.
Panneerselvam J, Govindasamy C, Pitchappan R, 2022. Salivary biomarkers in oral squamous cell carcinoma: Current evidence and future prospects. Oral Oncology 129, 105864.
Ramadan M, El-Sayed A, Hassan A, 2024. Clinical challenges in the diagnosis and management of oral squamous cell carcinoma. Oral Diseases 30, 2145–2158.
Riley RS, June CH, Langer R, Mitchell MJ. 2019. Delivery technologies for cancer immunotherapy. Nature Reviews Drug Discovery 18(3), 175–196. https://doi.org/10.1038/s41573-018-0006-z
Rodríguez-Molinero J, Migueláñez-Medrán BC, Puche-Torres M, Marí-Roig A, Ferrandis-Perry S, Sáez-Yuguero MR, López-López J. 2022. Advances in the diagnosis, monitoring, and progression of oral cancer through saliva: An update. Disease Markers, 2022, Article 2739869. https://doi.org/10.1155/2022/2739869
Scholtz B, Horváth J, Tar I, Kiss C, Márton IJ. 2022. Salivary miR-31-5p, miR-345-3p and miR-424-3p as diagnostic biomarkers in oral squamous cell carcinoma. Pathogens 11(2), 229. https://doi.org/10.3390/pathogens11020229
Schwendicke F, Samek W, Krois J. 2023. Artificial intelligence in dentistry: Chances and challenges. Journal of Dental Research 102(7), 769–778.
Shi J, Kantoff PW, Wooster R, Farokhzad OC. 2017. Cancer nanomedicine: Progress, challenges and opportunities. Nature Reviews Cancer 17(1), 20–37. https://doi.org/10.1038/nrc.2016.108
Shi J, Kantoff PW, Wooster R, Farokhzad OC. 2017. Cancer nanomedicine: Progress, challenges and opportunities. Nature Reviews Cancer 17(1), 20–37. https://doi.org/10.1038/nrc.2016.108
Snyder H. 2019. Literature review as a research methodology: An overview and guidelines. Journal of Business Research 104, 333–339.
Tan Y, Wang X, Li W, Zhang C, Yang Y, Li Y. 2023. Oral squamous cell carcinomas: State of the field and emerging directions. International Journal of Oral Science, 15.
Tan WS, Kuo H, Jiang CG, Lu MH, Lu YH, Wang YL, Wang CS, Vo TTT, Lee IT. 2025. Salivary biomarkers and their link to oncogenic signalling pathways in oral squamous cell carcinoma: Diagnostic and translational perspectives in a narrative review. Oncology Research 34(1), Article 6. https://doi.org/10.32604/or.2025.070871
Tang B, Huang R, Ma W. 2024. Advances in nanotechnology-based approaches for the treatment of head and neck squamous cell carcinoma. RSC Advances 14(52), 38668–38688. https://doi.org/10.1039/D4RA07193J
Topol EJ. 2019. High-performance medicine: The convergence of human and artificial intelligence. Nature Medicine 25(1), 44–56. https://doi.org/10.1038/s41591-018-0300-7
Torraco RJ. 2016. Writing integrative literature reviews: Using the past and present to explore the future. Human Resource Development Review 15(4), 404–428.
United States Food and Drug Administration (FDA). 2022. Drug Products, Including Biological Products, That Contain Nanomaterials: Guidance for Industry. Silver Spring, MD: U.S. Food and Drug Administration.
Usman S, Jamal A, Teh MT, Waseem A. 2021. Major molecular signaling pathways in oral squamous cell carcinoma: Therapeutic targets and molecular mechanisms. International Journal of Molecular Sciences 22(8), Article 4162. https://doi.org/10.3390/ijms22084162
Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, Pacey S, Baird R, Rosenfeld N. 2017. Liquid biopsies come of age: Towards implementation of circulating tumour DNA. Nature Reviews Cancer 17(4), 223–238. https://doi.org/10.1038/nrc.2017.7
Wu C, Zhang H, Li Y, 2025. Global burden and temporal trends of oral cancer: An updated epidemiological analysis. BMC Cancer 25, Article 84.
Zahiruddin WM, Abdullah N, Ismail N, 2024. Epidemiological trends and socioeconomic determinants of oral squamous cell carcinoma in South and Southeast Asia. BMC Oral Health 24, Article 317.
Zhang Y, Li X, Chen J, Wang Z, Liu H, Zhao L. 2024. Nanotechnology-enabled precision medicine for oral squamous cell carcinoma: Current progress and future perspectives. International Journal of Nanomedicine 19, 6421–6453.
Abhijeet Patnaik, S. Vidya, Sathyakumar Mayilvakanam*, Magesh Karuppur Thiagarajan, Aravindhan Ravi, Sivachandran Annamalai, Mitthra Suresh, 2026. Nanotechnology-driven diagnostics and therapeutics in oral squamous cell carcinoma: Emerging technologies, clinical translation and future perspectives. Int. J. Biosci., 28(6), 216-272.
Copyright © 2026 by the Authors. This article is an open access article and distributed under the terms and conditions of the Creative Commons Attribution 4.0 (CC BY 4.0) license.