Transport of 5-fluorouracil by funcionalized gold nanoparticles with antibodies against epidermal growth factor receptors (EGFR and HER2)

Author(s)

Raquel Bester Liszbinski

• Document type: Master's Dissertation
• Press: Botucatu. 2018-06-13.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2018-04-26
• Advisor: Ramon Kaneno

Abstract

Colorectal cancer (CRC) is the third most prevalent type of cancer in worldwide and is frequently associated with metastatic complications. Therapeutic strategies to treat those patients who do not respond to conventional chemotherapy is based on the application of monoclonal antibodies cetuximab or panitumumab, both directed targeting the epidermal growth factor receptor (EGFR). However, in some cases resistance is associated with an overexpression of HER2, another receptor belonging to the EGFR family. Therefore, this dissertation was designed to test the hypothesis that the combination of anti-EGFR and anti-HER antibodies will be able to reduce the escape of tumor cells, and that their association with antitumor drugs could improve the elimination of tumor cells. Then, our goal was to use gold nanoparticles (AuNP) for transporting 5-fluorouracil (5FU), addressing them to colorectal cancer cells by coating them with antibodies against the receptors of epidermal growth factor EGFR (ErbB-1) and HER2 (ErbB-2). Nanocarriers were tested in vitro by flow cytometry for their interaction and internalization by the colorectal cancer cell line HCT-116 and Caco-2, their ability to induce apoptosis/necrosis and stop cell proliferation. Our results show that AuNP produced and functionalized with the molecules of interest have spherical structure, however, some formulations showed agglomeration due to the incorporation of organic molecules. Biological assays showed that AuNP 5FU EGFR had a significant effect on cytotoxic activity by the recent apoptotic pathway when cells were exposed to the highest concentration tested independently of the time of exposure. As a result, cell proliferation was stopped at this same treatment and both phenomena were observed most clearly in the Caco-2 cell line, including demonstrating superior effect to chemotherapy in free form. (AU)

• FAPESP's process: 15/26729-2 - TRANSPORT OF 5-FLUOROURACIL BY FUNCIONALIZED GOLD NANOPARTICLES WITH ANTIBODIES AGAINST EPIDERMAL GROWTH FACTOR RECEPTORS (EGFR AND HER2)
• Grantee: Raquel Bester Liszbinski
• Support Opportunities: Scholarships in Brazil - Master