Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 133, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.111053
Keywords
Trastuzumab; Drug delivery system; Electrophoresis; Chromatography; MRI
Funding
- National Science Centre Poland NCN, Narodowe Centrum Nauki [2017/25/B/ST4/02481]
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This study aimed to investigate the Trastuzumab-dendrimer-fluorine drug delivery system by synthesizing and characterizing a series of fluorinated dendrimers. The results from electrophoresis, HPLC, and LC-MS techniques showed the potential and efficiency of the synthesized drug delivery system. Three-dimensional cell culture experiments and MRI measurements confirmed the efficacy of the novel system in treating breast cancer cells with Her-2 overexpression.
Trastuzumab is considered to be a fundamental drug for treatment of breast cancer with Her-2 overexpression (Her-2 positive cells). Trastuzumab is a monoclonal antibody that targets the Her-2 receptor. Trastuzumab treatment used in breast cancer therapy require a visualization to validate their delivery and response. The objective of this study was to investigate Trastuzumab-dendrimer-fluorine drug delivery system by synthesis and characterization of a series of fluorinated dendrimers. Materials and methods: Trastuzumab-dendrimer-fluorine drug delivery system is a covalent attachment of Trastuzumab to fluorinated dendrimers. We design synthesis and evaluate main product by using electrophoresis, HPLC and LC-MS techniques. We prepared three-dimensional breast cancer cell culture in bioreactor device. For the cell culture we used MCF-7 cells with Her-2 overexpression to study Trastuzumab-dendrimer-fluorine drug delivery system efficacy. We evaluate efficacy by Magnetic Resonance Imaging (MRI) relaxation time. Results: An analytical analysis showed that synthesis of Trastuzumab-dendrimer-fluorine drug delivery system is possible to obtain with a good yield. The results obtained indicated potential of Trastuzumab-dendrimer-fluorine drug delivery system is more efficient than trastuzumab alone. Chromatographic and electrophoretic separations showed that the synthetized conjugates were a Trastuzumab-dendrimer-fluorine drug delivery systems. The hight synthesis efficiency was found. The presence of molecules with lower masses than trastuzumab can have influence on efficiency. Conclusions: Trastuzumab-dendrimer-fluorine drug delivery system is a new form of Trastuzumab to treat breast cancer cells in vitro. Due to presence of F-19 nuclei the system can be monitored by MRI measurements.
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