Biomimetic nanoparticles coated with cell membranes: from design to diagnosis and therapy of Glioblastoma Multiforme (GMB)

• Grant number: 23/05755-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): January 01, 2024
• Effective date (End): December 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Valtencir Zucolotto
• Grantee: Raquel Riciati do Couto Vilela
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy, AP.TEM
• Associated scholarship(s): 24/21218-9 - Biomimetic nanoparticles for targeted drug delivery in glioblastoma therapy, BE.EP.PD

Abstract

Glioblastoma multiforme (GBM) is a malignant brain tumor with a poor long-term prognosis. Despite the aggressive standard of care that includes surgical resection, radiotherapy, and chemotherapy, its highly invasive nature and the high impermeability of the blood-brain barrier (BBB) make it difficult to determine tumor extent and deliver therapeutic agents to the brain appropriately. In addition to the resistance of cancer cells to anticancer drugs, the low stability and lack of specificity of some chemotherapy drugs limit their absorption and further affect their curative effect. In this sense, nanotechnology offers a promising alternative to fill the gaps in conventional GMB treatments, allowing the design and development of drug delivery systems with improved properties. Nanoparticles can also be designed to have multiple functions, such as simultaneous administration of chemotherapy and imaging agents, allowing more accurate and personalized diagnostic and treatment approaches. In this project, hollow mesoporous silica nanoparticles, incorporating a fluorophore in the silica structure, will be synthesized and loaded with the drug temozolomide (TMZ), for concomitant delivery to GMB cells. In order to escape the immune system and reach the tumor tissue, we will act with a biomimetic and bioinspired strategy that includes coating these nanosystems with cell membranes. This strategy offers specificity to the cells of interest, contributing to less toxicity in adjacent healthy cells. The non-invasive optical (fluorescence) imaging modality offered by the fluorophore allows the diagnosis of GMB and monitoring of tumor response to treatment in real-time, while targeted delivery and accumulation of the chemotherapeutic at the target site improves the balance between its effectiveness and toxicity. (AU)