Functionalized lipid vesicles for administration in the mammary ducts and localized treatment of breast cancer

• Grant number: 25/01264-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: January 31, 2030
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Giovanna Barros de Melo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

This project aims at developing and evaluating functionalized vesicular nanocarriers for the intraductal administration of a combination of cytotoxic drugs for treatment of localized forms of breast cancer, integrating greater selectivity and efficacy. It is justified by the gaps in the current breast cancer management strategies, including treatment of the non-invasive forms, such as intraductal carcinoma in situ (DCIS), which follows the same pattern of invasive forms (with chemotherapy, radiotherapy and surgery). Studies indicate that this standard of treatment is not sufficient for some cases but may be considered excessive in others due to the difficulty in reliably estimating the risk of progression to invasive forms. In addition, nanocarriers and the intraductal route can also potentially be applied to pre-tumor lesions, chemoprevention in high-risk populations and neoadjuvant treatment. The nanocarrier will be modified with folic acid to enhance the targeting of cytotoxic drugs to carcinoma cells, increasing selectivity and reducing local and systemic adverse effects. Coencapsulation of piplartine with a second cytotoxic drug, which will be defined in preliminary in vitro cytotoxicity potentiation studies, will be explored to reduce the dose of individual drugs, contributing to improve the safety profile and reduce resistance. The nanocarriers will be characterized using electron microscopy and dynamic light scattering. The effect of nanocoencapsulation and functionalization on the cytotoxic effect, selectivity and mechanism of action of the selected drugs will be evaluated in tumor cell lines and healthy breast cells grown in monolayer and in 3D co-culture models. Finally, a selected system will have its efficacy studied in an in vivo model. (AU)