Nano-Engineered Cetuximab-Copper Complexes for Targeted Drug Delivery in Head and Neck Cancer

Head and neck squamous cell carcinomas (HNSCCs) require precise treatments. Cetuximab (Ceb) targets EGFR, and copper (Cu) compounds show promise in cancer therapy. This study investigates Ceb-Cu-p-NC, a nanoengineered drug delivery system, designed for enhanced HNSCC treatment. The objective of this study is to evaluate the potential of Ceb-Cu-p-NC in HNSCC treatment.

Cu precursor, Ceb, poloxamer-407, and hyaluronic acid were used to synthesize Ceb-Cu-p- NC. Fluorescence microscopy and UV spectrophotometry were utilized to determine Ceb integration efficiency, cellular interactions, and drug concentration. Drug release was assessed via in-vitro studies at pH 5.4 and 7.4. Studies using A-253 cell lines were conducted to analyze cytotoxicity, viability, apoptosis, and cell cycle arrest.

In this study, Ceb-Cu-p-NC showed size reduction (85-120 nm) and zeta potential shift. The Ceb integration was 34.92% with 82.5% entrapment efficiency. Cytotoxicity studies revealed enhanced efficacy (IC50: 27.55 mg/mL - 51.47 mg/mL). Flow cytometry showed significant apoptosis and S-phase cell cycle arrest, with statistically significant results (p < 0.05).

Ceb conjugation to Cu-p-NC enhanced nanoparticle stability, reduced surface charge, and enabled targeted, controlled drug release. The formulation showed superior cytotoxicity, apoptosis induction, and S-phase arrest in A-253 cells compared to free Ceb, highlighting its potential as an effective targeted therapy for head and neck cancer.

Ceb-Cu-p-NC demonstrates targeted efficacy against HNSCCs, with controlled release, increased cytotoxicity, and apoptosis.