Breast cancer is the most frequently occurring cancer in women from Mexico and the world. The search of new therapeutic strategies against this cancer has focused on natural products, such as polyphenols, specifically flavonoids. In this context, our group has shown that (-)-epicatechin (a flavonoid) has an antiproliferative effect on cell lines of breast cancer. However, flavonoids are molecules typically prone to degrade when exposed to physical, chemical and biological factors, which limits its activity in vivo. Therefore, in this study we focus on developing and characterization (-)-epicatechin loaded chitosan nanoparticles (EC-Nps) and (-)-epicatechin loaded chitosan nanoparticles conjugated with antibody Mammaglobin-A (EC-MamA-Nps) for to evaluate their anticancer activity in vivo. The effects of these nanoparticles on ROS production and apoptosis induction in the tumour were investigated too. Methods: Nanoparticles were prepared by the supramolecular self-assemble process followed by anti-Mammaglobin A antibody conjugation was do using carbodiimide chemistry. The nanoparticles obtained were characterized by size, polydispersity index, Z potential, Fourier transform infrared spectroscopy and the morphology was established by confocal microscopy. The conjugation of antibody to nanoparticles was determides by SDS-PAGE. Antitumoral effect was evaluate in a syngeneic transplant model on BALB/c mice. ROS production in tumours was determined by the values of biomarkers of oxidative damage such as carbonyl groups, quantification of formazan by nitroblue tetrazolium reduction (NBT), malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), also the activity of glutathione peroxidase (GSH-Px) was analyzed. Finally, DNA fragmentation assay and caspase activation was performed to determine the induction of apoptosis Results: We obtained nanoparticles with size of 200 nm, zeta potential negative, IP smaller than 0.2 and morphology was spherical shape. And eventually, the differences in biomarkers of oxidative damage (MDA, TBARS and NBT) and decreasing of GSH-Px activity were observed in tumours of mice treated with EC-MamA-Nps. Conclusion: The data obtained in this study, suggest that the antitumor activity of nanoparticles EC-MamA-Nps is mediated by an induction of apoptosis and increase in the production of ROS.

In vivo antitumor effect of anti-Mammaglobin-A antibody conjugated to (-)-epicatechin loaded chitosan nanoparticles in a murine model of breast cancer

256th National Meeting (2018)

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