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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Discussion: 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.

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