Effect of Cetuximab-Conjugated Gold Nanoparticles on the Cytotoxicity and Phenotypic Evolution of Colorectal Cancer Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-01, Vol.26 (3), p.567
• Main Authors: El Hallal, Ralph, Lyu, Nana, Wang, Yuling
• Format: Article
• Language: English
• Subjects: Adhesion; Antineoplastic Agents, Immunological - administration & dosage; Biomarkers; Biomarkers, Tumor - metabolism; Cancer; Cancer therapies; CD146 Antigen - metabolism; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell surface; Cell Survival - drug effects; cetuximab; Cetuximab - administration & dosage; Cholecystokinin; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cytotoxicity; Epidermal growth factor; epidermal growth factor receptor; Epidermal growth factor receptors; Epithelial Cell Adhesion Molecule - metabolism; Epithelial cells; Evolution & development; Flow cytometry; Gold; gold nanoparticles; Growth factors; Heterogeneity; HT29 Cells; Humans; Immunotherapy; Ligands; Medical prognosis; Melanoma; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - ultrastructure; Metastases; Metastasis; Monoclonal antibodies; Mutation; Nanoconjugates - administration & dosage; Nanoconjugates - ultrastructure; Nanoparticles; Particle Size; Phenotype; Prognosis; Raman spectra; Raman spectroscopy; Receptor, ErbB-3 - metabolism; Signal Transduction - drug effects; Spectroscopy; Spectrum analysis; Spectrum Analysis, Raman; surface-enhanced Raman scattering/spectroscopy; Targeted cancer therapy; Toxicity testing
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26030567

Epidermal growth factor receptor (EGFR) is estimated to be overexpressed in 60~80% of colorectal cancer (CRC), which is associated with a poor prognosis. Anti-EGFR targeted monoclonal antibodies (cetuximab and panitumumab) have played an important role in the treatment of metastatic CRC. However, the therapeutic response of anti-EGFR monoclonal antibodies is limited due to multiple resistance mechanisms. With the discovery of new functions for gold nanoparticles (AuNPs), we hypothesize that cetuximab-conjugated AuNPs (cetuximab-AuNPs) will not only improve the cytotoxicity for cancer cells, but also introduce expression change of the related biomarkers on cancer cell surface. In this contribution, we investigated the size-dependent cytotoxicity of cetuximab-AuNPs to CRC cell line (HT-29), while also monitored the expression of cell surface biomarkers in response to treatment with cetuximab and cetuximab-AuNPs. AuNPs with the size of 60 nm showed the highest impact for cell cytotoxicity, which was tested by cell counting kit-8 (CCK-8) assay. Three cell surface biomarkers including epithelial cell adhesion molecule (EpCAM), melanoma cell adhesion molecule (MCAM), and human epidermal growth factor receptor-3 (HER-3) were found to be expressed at higher heterogeneity when cetuximab was conjugated to AuNPs. Both surface-enhanced Raman scattering/spectroscopy (SERS) and flow cytometry demonstrated the correlation of cell surface biomarkers in response to the drug treatment. We thus believe this study provides powerful potential for drug-conjugated AuNPs to enhance cancer prognosis and therapy.