Nanocarrier-Mediated Chemotherapy for Oral Squamous Cell Carcinoma: Pharmacokinetics, Tumor Targeting, and Safety

Oral squamous cell carcinoma often fails chemotherapy because effective intratumoral exposure cannot be sustained without unacceptable systemic toxicity, a mismatch amplified by salivary washout and mucosal barriers in the oral cavity. This narrative review reframes nanocarrier chemotherapy as exposure engineering, defined here as the deliberate design of delivery systems to control the spatial and temporal distribution of drug concentrations across clinically relevant compartments (tumor, regional lymph nodes, and blood), and integrates three co-primary domains: Pharmacokinetics, tumor-targeting with intratumoral coverage, and route-matched safety-by-design. This review emphasizes defining success by compartment-level exposure outcomes, especially tumor and regional lymph-node delivery with minimal systemic peaks, using a transmucosal cisplatin patch paradigm as a translational benchmark. The review also shifts evaluation from accumulation to coverage by prioritizing spatial uniformity metrics that capture underdosed niches. Finally, it extends safety requirements to externally triggered platforms through modality-specific dosimetry and collateral injury surveillance, and proposes a standardization checklist to improve reproducibility and human-forward translation.