Research on enzymatic co-assembly nanomedicine in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) represents the predominant form of malignancy within the head and neck region, accounting for more than 90 ​% of all oral cavity tumors. OSC cells commonly overexpress epidermal growth factor receptor (EGFR), which is closely associated with the development, progression, and differentiation of tumors. Despite surgery and chemotherapy being the primary therapeutic interventions for OSCC, their efficacy is suboptimal compared with that of other oral malignancies. We engineered a polypeptide molecule (HCPT-G D F D F D pYERGD, designated HP), which features the chemotherapeutic agent 10-hydroxycamptothecin (HCPT) at its N-terminus and the tumor-homing ligand Arginine-Glycine-Aspartic acid (RGD) at its C-terminus. The RGD moiety confers upon the polypeptide the ability to co-target cancer cells synergistically. The EGFR inhibitor cetuximab was co-assembled with HP via an enzymatic catalysis co-assembly technique to create a nanofibrillar structure, resulting in antibody‒polypeptide coassembly. In vitro assays have demonstrated that the co-assembled nanomedicine exhibits high affinity for OSCC cells, is efficiently internalized, and elicits potent inhibitory effects. Furthermore, bioinformatics analysis suggested that the co-assembled nanomedicine downregulated genes enriched in the PI3K-Akt signaling cascade. The co-assembled nanomedicine dramatically reduces cancer while sparing negative effects, as shown by in vivo animal models. This research endeavors to develop a new nanomedicine delivery platform that integrates molecular targeting with efficient intracellular drug delivery. This system not only markedly augments the therapeutic efficacy of the chemotherapeutic agent HCPT but also substantially mitigates patient adverse effects, thus offering a more secure and efficacious therapeutic strategy for the management of OSCC. • Oral squamous cell carcinoma (OSCC) can exhibit heightened levels of epidermal growth factor receptor expression. • The overexpression of EGFR is connected to the occurrence, development, and diversity of tumors. • Enzyme-Mediated Co-assembly Nanodrugs with Molecular Targeting Capabilities. • Co-assembled nanomedicine exhibits significant anticancer efficacy. • Co-assembled nanomedicine can induce enrichment of genes related to tumors.