Desenvolvimento e avaliação pré-Clínica de nanopartículas poliméricas decoradas com bevacizumab e carregadas com paclitaxel e docetaxel radiomarcadas com tecnécio-99 metaestável como nanoteragnóstico para o câncer de mama

Abstract

Breast cancer is the most common cancer in women worldwide. In Brazil, breast cancer is responsible for 14 thousand deaths/year with an incidence of 277,3 cases per 100 thousand women. several types of breast cancer and molecular classification is currently used to differentiate subtypes, and growth is an additional factor in this classification. Among the main limitations related to breast cancer is its accurate diagnosis and effective treatment. In this context, the development of more effective, safe and efficient medicines becomes vital. In this context, the use of nanotechnology represents development and a strategic advance, since nanoparticles can be developed to increase the drug release profile, as well as improve targeting to a specific site (tumor) or even to intracellular targets to reduce toxicity. Currently, two drugs stand out in breast cancer therapy: Paclitaxel® and Docetaxel®. Although they are very similar in their mechanism of action: i) they prevent the uncontrolled division of cancer cells and ii) they induce apoptosis, the pharmacotherapeutic behavior is quite different, since Docetaxel® is a programming-independent drug (molecular biology and genetic engineering combined in the design of systems to create living organisms with desired characteristics or new functionalities, with a variety of potential applications), resulting in very distinct toxicological profiles. Finally, and aiming to improve drug targeting, modern techniques for decorating polymeric nanoparticles have been used, with emphasis on the use of monoclonal antibodies as decorating agents, that is, agents responsible for binding antibodies to the site of interest due to its surface properties. Based on this, the use of Bevacizumab (Avastin®), a monoclonal antibody with the ability to specifically bind to VEGF (Vascular Endothelial Growth Factor), a protein that presents a crucial role in the growth and formation of new blood vessels (angiogenesis). In other words, Bevacizumab reduces the formation of new blood vessels within the tumor, which limits its supply of nutrients and oxygen, which can lead to a decrease in tumor growth and even tumor regression in some cases in therapies. Based on these characteristics, a nanoparticle containing the drugs Paclitaxel® and Docetaxel® was developed using the double emulsion methodology and the nanoparticles were subsequently functionalized with Bevacizumab with the carbodiimide reaction. The nanoparticles showed significant results and high encapsulation efficiency, observed at therapeutic concentrations in target tissues. The results of the analyzes carried out provided information on efficacy, safety, optimizing therapeutic and diagnostic applications in cancer treatment. Based on these results, it was possible to evaluate the clinical potential of paclitaxel and docetaxel nanoparticles decorated with Bevacizumab.