The use if RNA-based nano formulations to improve the efficacy of breast cancer treatment and reduce therapy-induced cardiotoxicity

• Grant number: 17/50029-6
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2017
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Biology
• Agreement: UNC Charlotte
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Roger Chammas
• Grantee: Roger Chammas
• Principal researcher abroad: Kirill Afonin
• Institution abroad: University of North Carolina at Charlotte (UNCC), United States
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment, AP.TEM

Abstract

Chemotherapy and radiotherapy are extremely potent tools to treat breast cancer, but they cause several side effects. Doxorubicin is widely used to treat this disease, but its therapeutic effects are limited by cardiotoxicity. Strategies to increase its anti-tumor effect with a lower dose and diminish the side effects are extremely desirable. A potential candidate for this strategy is the platelet-activating factor (PAF), a potent pro-inflammatory phospholipid mediator found in several tumors and cardiomyopathies, through the activation of its receptor PAF-R. PAF is synthesized primarily through lipid remodeling, and depends upon the controlled activity of Iysophosphatidylcholine acyltransferases (LPCAT 1-4), which are involved in mammary tumorigenesis. In this project, we intend to investigate whether PAF attenuation by LPCAT1-4 inhibition, through multifunctional RNA nanoparticles decorated with PAF-R monoclonal antibody for controlled targeted delivery of multiple therapeutic siRNAs would impair human breast cancer progression in vitro and in vivo. The synergistic approach using nanoparticles in conjunction with doxorubicin and/or radiotherapy may represent a promissory therapeutic strategy to inhibit breast cancer growth and progression with minimal cardio-toxic effects. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KE, WEINA; HONG, ENPING; SAITO, RENATA F.; RANGEL, MARIA CRISTINA; WANG, JIAN; VIARD, MATHIAS; RICHARDSON, MELINA; KHISAMUTDINOV, EMIL F.; PANIGAJ, MARTIN; DOKHOLYAN, V, NIKOLAY; et al. RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-B in human cells. Nucleic Acids Research, v. 47, n. 3, p. 1350-1361, FEB 20 2019. (17/50029-6, 15/22814-5)

SAITO, RENATA F.; RANGEL, MARIA CRISTINA; HALMAN, JUSTIN R.; CHANDLER, MORGAN; DE SOUSA ANDRADE, LUCIANA NOGUEIRA; ODETE-BUSTOS, SILVINA; FURUYA, TATIANE KATSUE; MURILLO CARRASCO, ALEXIS GERMAN; CHAVES-FILHO, ADRIANO B.; YOSHINAGA, MARCOS Y.; et al. Simultaneous silencing of lysophosphatidylcholine acyltransferases 1-4 by nucleic acid nanoparticles (NANPs) improves radiation response of melanoma cells. Nanomedicine-Nanotechnology Biology and Medicine, v. 36, AUG 2021. (13/07937-8, 17/50029-6)