Biomimetic Nanoparticles for Targeted Delivery Across the Blood-Brain Barrier: Application in Advanced In Vitro Models

• Grant number: 25/07870-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Valtencir Zucolotto
• Grantee: Marylyn Setsuko Arai
• Supervisor: Andreas Hierlemann
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: Ethz Department Of Biosystems Science And Engineering, Switzerland
• Associated to the scholarship: 24/05979-0 - Biomimetic luminescent nanoparticles based on cell-membrane coating for glioblastoma theranostics., BP.PD

Abstract

Delivering therapeutic agents to the brain remains a major challenge due to the blood-brain barrier (BBB), a selective interface that restricts molecular transport into the central nervous system (CNS). Nanotechnology offers promising solutions, particularly through biomimetic carriers that enhance brain targeting and immune evasion. This project aims to evaluate the biological interaction, transport behavior, and theranostic potential of biomimetic upconverting nanoparticles (BUCNPs) developed at GNano (IFSC/USP). These consist of UCNPs coated with glioblastoma cell membranes to improve stealth properties and tumor selectivity. A drug-loaded version (BUCNPs:TMZ) enables simultaneous delivery of temozolomide and real-time luminescence-based tracking, facilitated by the particles' near-infrared excitation and anti-Stokes emission. Following successful application in 2D glioblastoma cells, the BUCNPs will now be tested in more physiologically relevant systems at the Bio Engineering Laboratory of Prof. Andreas Hierlemann (ETH Zurich), using 3D glioma spheroids, BBB spheroids, and BBB-on-a-chip platforms. These models will be used to assess BUCNP-cell interaction, barrier crossing, tumor targeting, and treatment efficacy. Beyond validating a new brain-targeted theranostic platform, this research will provide advanced training in 3D in vitro tissue modeling and foster collaboration between GNano and ETH Zurich. (AU)