Multimodal Imaging of Brain Metastasis-Derived Extracellular Vesicles Using Superparamagnetic Iron Oxide Nanoparticle...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Extracellular vesicles (EVs) play a key role in brain metastasis (BM) by forming pre-metastatic niches.
• Tracking the distribution and interaction of EVs in vivo is a significant challenge in cancer research.

Purpose of the Study:

• To develop and validate a method for labeling BM-derived EVs using superparamagnetic iron oxide nanoparticles (SPIONs).
• To enable visualization and tracking of labeled EVs in vivo using magnetic resonance imaging (MRI).

Main Methods:

• Evaluated three SPION variants for labeling patient-derived BM cell lines.
• Characterized labeled EVs using TEM, iron assays, DLS, and NTA.
• Assessed functionality and visualization in fetal rat brain organoids (FRBOs) and in vivo mouse models using MRI and Prussian blue staining.

Main Results:

• Uncoated 5 nm SPIONs achieved >90% cell labeling efficiency within 24 hours without impacting cell growth.
• SPIONs were incorporated into EVs, maintaining their size, and enabling visualization via MRI.
• In vivo MRI confirmed successful tracking of labeled EVs after intramuscular injection.

Conclusions:

• Established a reliable protocol for SPION-based labeling of BM-derived EVs.
• The developed method allows for visualization of EVs from subcellular to tissue levels.
• This tool facilitates in vivo spatial tracking of BM-EVs and investigation of their role in metastasis.