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Investigation of molecular mechanisms induced by nanoestrutured vectors for transfection of genes in spheroid tumor cultures

Grant number: 19/06023-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2019
Effective date (End): April 30, 2023
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Marcelo Bispo de Jesus
Grantee:Raquel Bester Liszbinski
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Breast Cancer is the second most common Cancer in incidence and mortality among females and according to national and international health organizations, this number has increased in recent years. The development of new therapies for the treatment of Cancer is necessary because of this increasing number of cases and the difficulty of effective treatments. Among the molecular mechanisms involved in tumor biology, the Wnt and Transforming Growth Factor ² (TGF-²) pathway, responsible for the regulation of cell proliferation and differentiation processes and, when altered, promote tumorigenesis. Genetic editing by CRISPR Cas9, we can silence these genes that cause the disorganization of cellular functions, in the case of Wnt and TGF-², we can use Transforming Growth-Interacting Factor (TGIF) that acts increasing cell signaling in Triple Negative Breast Tumors (TNBC) which results in poor clinical prognosis of patients, however, that of genes inside the cells is hampered by the plasma membrane, necessitating vectors of transport. In recent years, nanotechnology has shown excellence in the properties of protection and delivery of molecules, especially solid lipid nanoparticles (NLS), because in addition to the efficient delivery of genes, its structure has biocompatible lipid components. Studies on the biological mechanisms and effects triggered by nanoparticles (NP) are being increasingly required for their potential applicability. In this project we will search to understand the internalization and intracellular trafficking of NLS in the gene edition by CRISPR/cas9 for TGIF gene silencing to MDA-MB-231 (TNBC) breast tumor cells in spheroid culture (3D culture), analyzing the effects of editing. The evaluations of these biological mechanisms may provide an understanding of the molecular mechanisms of particle internalization for the CRISPR/Cas9 gene editing tool, in addition to promoting the silencing of the TGIF gene. (AU)