Journal
MOLECULES
Volume 26, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/molecules26030567
Keywords
epidermal growth factor receptor; colorectal cancer; cetuximab; cytotoxicity; gold nanoparticles; surface-enhanced Raman scattering; spectroscopy; phenotypes
Funding
- Macquarie University Research Seeding Grant
- Major Project in Molecular Sciences of Macquarie University [CBMS 881]
- International Macquarie University Research Excellence Scholarship
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The study demonstrates that cetuximab-conjugated gold nanoparticles exhibit cytotoxic effects on colorectal cancer cells and alter the expression of related biomarkers on cancer cell surfaces. Gold nanoparticles with a size of 60 nm showed the greatest cytotoxic impact, while treatment with cetuximab-AuNPs resulted in increased heterogeneity in the expression of surface biomarkers. Both surface-enhanced Raman scattering/spectroscopy (SERS) and flow cytometry confirmed the correlation between the cell surface biomarkers and drug treatment, suggesting a potential for drug-conjugated AuNPs to enhance cancer prognosis and therapy.
Epidermal growth factor receptor (EGFR) is estimated to be overexpressed in 60 similar to 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.
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