Biomimetic Cascade‐Targeted Nanoplatform for Fluorescent Localization and Eradication of Oral Squamous Cell Carcinoma

Abstract Nanodrug delivery systems hold tremendous promise for tumor therapy; however, challenges such as precise targeting, rapid drug release, and efficient drug utilization remain unresolved. Here, a biomimetic cascade‐targeted nanoplatform (graphene quantum dots‐RRL‐Evodiamine, GRE) that uniquely integrates both active and passive targeting strategies with a reactive oxygen species (ROS)‐responsive release mechanism is developed. The system employs RRL peptides for active recognition of overexpressed heat shock protein 70 (Hsp70) on oral squamous cell carcinoma (OSCC) membranes, mimicking natural ligand—receptor interactions; and thereby, imparting biomimetic targeting capability; while, Evodiamine (EVO) is covalently anchored to RRL‐modified graphene quantum dots (GQDs) through a ROS‐labile thioketal (TK) linker, ensuring precise and timely drug release. Moreover, the inherent fluorescence of GQDs enables real‐time tracking of drug delivery. Remarkably, GRE administration achieves 83% tumor volume reduction in vivo, outperforming free EVO (25%) by 3.3‐fold, underscoring the system's superior therapeutic efficacy. This multifunctional system establishes a paradigm for OSCC treatment by uniting biomimetic targeting, ROS‐triggered release, and integrated imaging into a single nanoplatform.