Development of target-directed immunomodulatory nanoparticles for triple negative breast cancer cells

• Grant number: 24/05464-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Luíza Maria Peres Simas Borges
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Breast cancer is the most common malignant neoplasm in women worldwide and one of the leading causes of death for women in developed countries. The main treatment strategy is chemotherapy followed by radiotherapy, but resistance is frequent, resulting in a 46% rate of metastasis, 25% recurrence after surgery and 75% mortality. The use of monoclonal antibodies to inhibit immune checkpoints has revolutionized medical practice, providing an alternative treatment for many patients. Despite this, the vast majority are still refractory to existing treatments. This justifies the development of new therapeutic strategies. In this proposal, we will develop immunomodulatory nanoparticles that make it possible to deliver a potent immunomodulator directly to the tumor site. These particles, called virus-like particles, are derived from viral capsids and can be decorated with tropism-targeting ligands and immunomodulatory proteins. We plan to prospect new selective ligands for triple-negative breast cancer cells from phage libraries, using animal models challenged with human primary tumors. These new ligands will be used to decorate immunomodulatory particles containing 4-1BBL. The immunomodulatory particles will be characterized to verify selective binding to tumor cells and antitumor immunomodulatory effect in cell culture assays. This project could contribute to the development of innovative proposals for the therapy of triple negative breast cancer.