Targeted Gene Therapy for Gliomas via Engineered Lipid Nanoparticle Systems

• Grant number: 25/15734-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 17, 2025
• End date: November 16, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Jonatas Lobato Duarte
• Supervisor: Saigopalakrishna Yerneni
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Mayo Clinic College Of Medicine, United States
• Associated to the scholarship: 22/11101-1 - Exploring the potential of functionalized nanostructured lipid carriers loaded with cetuximab dispersed in thermo-responsive mucoadhesive hydrogels for the intranasal administration of temozolomide and ellagic acid in the treatment of GBM, BP.PD

Abstract

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), represent some of the most aggressive and intractable cancers of the central nervous system. Current standard-of-care therapies are limited by non-specificity, inability to penetrate the blood-brain barrier (BBB), and high recurrence rates. Gene therapy offers a transformative potential by enabling targeted genetic modulation of glioma cells. However, safe and effective delivery of gene-editing cargo across the BBB remains a formidable challenge. Lipid nanoparticles (LNPs) have emerged as a clinically validated platform for nucleic acid delivery, notably in mRNA vaccines and siRNA therapies. This project proposes to develop and optimize LNP formulations specifically designed for efficient, targeted, and safe gene therapy delivery to gliomas. We will employ a modular design strategy integrating glioma-targeting ligands, BBB-penetrating features, and payload versatility (e.g., mRNA, siRNA, CRISPR components). The proposed work will be organized into three specific aims: (1) Develop and characterize a library of LNPs optimized for BBB penetration and glioma cell uptake, (2) Evaluate in vitro transfection efficiency and therapeutic potential using patient-derived glioma models, and (3) Validate biodistribution, safety, and therapeutic efficacy in orthotopic glioma mouse models. By systematically engineering and validating LNP systems for glioma-targeted gene therapy, this project aims to lay the groundwork for next-generation, precision nanomedicines for brain tumors.