Investigations of the therapeutic and cytotoxic effects of metallic nanoparticles under the influence of biomolecular coronas

Abstract

Recently, metallic nanoparticles have emerged as a promising biotechnological system for the transport and delivery of drugs and biomolecules for a myriad biomedical application, pointing as an innovative solution to the challenges currently unmet in clinical standards. However, in contact with biological fluids, nanoparticles are quickly covered by biomacromolecules that form the biomolecular corona, which significantly modifies the biological identity of the material, changing what interacts with cells and immune system. The composition of complex creates a unique biological identify that is directly related to the biological environment that nanoparticle interacts with, for example, tumor patients present several changes in their plasma composition profiles and when it comes to cachectic patients this change is very significant. The detailed understanding of nanoparticle-protein interactions and the consequences of the existence of biomolecular corona in a series of biological events are of unique relevance to designing nanomaterials with the desired toxicological profiles and therapeutic effects. In this context, this Ph.D. project proposes the incubation of metallic gold and silver nanoparticles in plasma environments of healthy donors and breast cancer patients to understand the role of pathology in the formation of the biomolecular corona and impact on biological events, in addition to investigating these effects in cachectic rats with Walker 256 carcinosarcoma in vitro and in vivo. For the analysis of biological events, this complex will be inserted into human breast cancer cell lines and macrophages, as well as Walker 256 carcinosarcoma cells, to understand the effects on cytotoxicity, cellular internalization, inflammation and tumorigenesis. Inflammation, as well as the impact of corona on tumorigenesis will be investigated in a rat model with Walker 256 carcinosarcoma, aiming to understand at a systemic level how coronas influence the identity and effect of nanoparticles. It is expected to demonstrate that the different metallic nanoparticles induce the formation of protein coronas of different nature that will have different consequences in the biological events that will be investigated. The knowledge generated in a more relevant environment regarding its clinical application will help not only in the development of more efficient nanomaterials, but also safer.