Use of hybrid nanoparticles functionalized with dual-responsive aptamers: immunotherapy and identification of circulating breast tumor cells.

• Grant number: 24/03294-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Sandra Martha Gomes Dias
• Grantee: Cyro von Zuben de Valega Negrão
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 21/05726-6 - Metabolism in the microenvironment and the role of metabolic exchanges in tumor progression, AP.TEM

Abstract

One of the main contributing factors to the high mortality associated with cancer is metastasis. In this context, circulating tumor cells (CTCs) play a crucial role in understanding metastatic cancer, especially in the context of breast neoplasia, where their presence is strongly correlated with an unfavorable prognosis. Thus, early detection of CTCs emerges as a crucial tool in clinical practice to improve patient survival. Additionally, CTCs represent essential targets for technological advancements and therapeutic innovations. This research project stems from the continuity of the candidate's doctoral work, during which a hybrid nanoparticle (NP) designed to identify HER-2+ breast cancer cells was developed and characterized. This project's foundation is using an iron oxide NP encapsulated in a PDMAEMA-b-PMPC block copolymer and functionalized with dual-response aptamers, named IONPPP. The choice of aptamers (apt), low-cost oligonucleotides with high specificity for membrane receptors, is justified by their ease of functionalization on NP surfaces. The project's first phase aims at CTC identification, with IONPPP functionalized with apt-antiHER-2 and apt-antiEpCAM markers for breast cancer CTCs. In the second phase, we will explore the immunotherapeutic potential of the NP in treating metastatic breast cancer by functionalizing it with apt-antiCD16 to activate antibody-dependent cellular cytotoxicity (ADCC) in natural killer (NK) cells. Various methodologies have been proposed to validate the intended biological application. For CTC detection, these include ex vivo experiments to analyze the capture of these cells in different solutions (saline, murine and human blood), and in vivo experiments to verify CTC capture in a clinically relevant model. The immunotherapeutic approach begins by verifying the activation of human NK cells by IONPPP, followed by assessing the dual immunotherapeutic response (CTC identification and NK cell activation) in vivo, using murine models with a humanized immune response. Therefore, based on previous work published by the group, this project proposes a comprehensive biological application of the NP for breast cancer diagnosis and immunotherapy.