Precision Nanotechnology in Oral Oncology: From Biomarker-Guided Targeting to AI-Driven Theranostics.

Oral squamous cell carcinoma (OSCC) is a serious malignancy characterised by poor outcomes, late identification, therapeutic resistance, and the adverse effects associated with radiation therapy, surgery, and chemotherapy. Nanotechnology-based drug delivery provides modular approaches that improve intratumoral accumulation, safeguard payloads, and facilitate controlled release, all while reducing off-target damage. This review compiles the latest findings in the field of oral cancer targeting magnetic nanomaterials, cyclodextrins, quantum dots, dendrimers, and metallic/inorganic platforms (metal-organic frameworks). Mechanistic innovations encompass both passive and active targeting strategies (e.g., EGFR, folate, CD44), stimuliresponsive mechanisms (pH, enzyme), and precision systems guided by salivary biomarkers (e.g., IL-8, CYFRA 21-1), ultimately leading to enhanced therapeutic indices and real-time theranostic monitoring. Innovative approaches use AI-driven design, biosensor-facilitated early detection, and Nanovaccine/immunenanomedicine techniques to personalise treatment in the multifaceted oral tumour microenvironment. Translational challenges remain, including heterogeneous EPR effects, nanotoxicology (encompassing autophagy and ROS pathways), manufacturing scale-up, and regulatory standardisation. These issues require the development of robust pharmacology-toxicity frameworks and biomarker-driven clinical trials. Nanocarriers of the future may revolutionise OSCC treatment by bringing together materials science, tumour biology, and genetic and salivary signals that are unique to each patient. This will allow for safer, more effective, and quantifiable precision therapies.