Chitosan-modified manganese oxide-conjugated methotrexate nanoparticles delivering 5-aminolevulinic acid as a dual-modal T1-T2* MRI contrast agent in U87MG cell detection

MAGMA. 2024 Oct;37(5):909-924. doi: 10.1007/s10334-024-01169-4. Epub 2024 May 25.

Abstract

Objective: Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans.

Materials and methods: The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images.

Results: The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect.

Conclusion: This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

Keywords: Cancer targeting; Drug delivery; Glioblastoma multiforme; MRI contrast agent; Manganese oxide (MnO2) nanoparticles.

MeSH terms

  • Aminolevulinic Acid* / chemistry
  • Animals
  • Brain Neoplasms / diagnostic imaging
  • Cell Line, Tumor
  • Cell Survival* / drug effects
  • Chitosan* / chemistry
  • Contrast Media* / chemistry
  • Glioblastoma* / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Manganese Compounds* / chemistry
  • Methotrexate* / administration & dosage
  • Methotrexate* / chemistry
  • Methotrexate* / pharmacology
  • Mice
  • NIH 3T3 Cells
  • Nanoparticles* / chemistry
  • Oxides* / chemistry

Substances

  • Methotrexate
  • Contrast Media
  • Manganese Compounds
  • Chitosan
  • manganese oxide
  • Oxides
  • Aminolevulinic Acid