Dual-Purpose 5-Aminolevulinic Acid-Loaded Iron Oxide Nanoparticles: Enhancing Radiotherapy and Mri in Glioblastoma Publisher



Ahrabi H ; Hataminia F ; Mortezazadeh T ; Ghanbari H ; Malekzadeh R ; Ebrahimpour A ; Geraily G
Source: Journal of Drug Delivery Science and Technology Published:2026

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and common primary malignant brain tumor in adults, with treatment hampered by poor drug delivery, unclear tumor margins, and radio-resistance. Nanoparticles (NPs) offer promising therapeutic and diagnostic potential due to their ability to accumulate selectively in tumor tissue via the enhanced permeability and retention (EPR) effect. This study presents dual-purpose iron oxide NPs (Fe3O4 NPs) functionalized with bovine serum albumin (BSA) and loaded with 5-aminolevulinic acid (ALA) as a radiosensitizer and MRI contrast agent for GBM. Fe3O4-BSA/ALA NPs were synthesized using co-precipitation, BSA coating, and ALA loading via freeze-thawing and ultrasonic methods. Characterization via FTIR, DLS, Zeta potential, and TEM confirmed their successful synthesis and stability. In vitro , Fe3O4-BSA/ALA NPs enhanced tumor cell death by 24.13 ± 5.59 % when combined with radiation therapy (RT), as measured by the Alamar Blue assay and flow cytometry. As MRI contrast agents, these NPs showed significant negative contrast enhancement with r2 values of 51.08 and 28.14 s-1 mM−1 for Fe3O4-BSA and Fe3O4-BSA/ALA, respectively. In vivo, bio-distribution studies demonstrated targeted tumor accumulation with minimal liver uptake. Anti-tumor efficacy studies revealed that Fe3O4-BSA/ALA NPs combined with RT significantly inhibited tumor growth and improved survival rates compared to other treatment groups. These results suggest that Fe3O4-BSA/ALA NPs could be a promising theranostic agent for both radiotherapy and MRI imaging in glioblastoma treatment. © 2025 Elsevier B.V.