Scholarship 22/08076-5 - Neoplasias mamárias, Lipossomos - BV FAPESP
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EVALUATION OF THE ANTITUMOR POTENTIAL OF [Ru(dmp)(dppe)2]PF6 NANOENCAPSULATED IN LIPOSOME IN A MURINE BREAST CANCER MODEL

Grant number: 22/08076-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date until: August 01, 2023
End date until: July 31, 2025
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Alzir Azevedo Batista
Grantee:Heloiza Diniz Nicolella
Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Associated research grant:17/15850-0 - X-ray diffraction as a tool in potential drug development, AP.TEM

Abstract

Cancer is the second most frequent cause of death in the world and shows a tendency to increase in incidence in the coming years, with breast cancer being one of the most incidents, with expressive numbers of cases in Brazil. Among the subtypes of breast cancer, the triple-negative one stands out for its aggressive behavior and poor prognosis, in addition to the absence of a therapy with broad efficacy. This scenario reinforces the need to find new effective treatments, targeting changes in the molecular biology of tumor cells. Thus, the use of liposomes loaded with cytotoxic substance constitutes a promising alternative to solve this adversity. In this sense, the ruthenium complex [Ru(dmp)(dppe)2]PF6 proves to be an interesting candidate for an antitumor agent to be encapsulated in liposome, since it showed significant cytotoxicity and selectivity in assays with breast cancer cell lines. Thus, the present study aims to evaluate the antitumor efficacy of the liposome containing [Ru(dmp)(dppe)2]PF6 in an orthotopic model of breast cancer, through analyzes of tumor volume and mass, tumor histology and mitotic frequency. The molecular signaling pathways involved in the antitumor action of the liposome containing [Ru(dmp)(dppe)2]PF6 will be investigated considering the expression levels of STAT, NF-kB, PI3K, AKT, mTOR, ³-H2AX, caspases -3, -8 and -9 and topoisomerases I and II, important for the tumorigenesis of triple-negative breast cancer, using quantitative real-time PCR and immunohistochemistry. different organs, through the evaluation of tissue mass, serum levels of hepatic and renal markers, and genotoxicity in hepatocytes. These results will contribute to a better understanding of the mechanisms of action involved in the cytotoxicity of the ruthenium complex in question, as well as to enable new, more effective and safer therapeutic strategies in the treatment of breast cancer.

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