Development of MRI/NIRF 'activatable' multimodal imaging probe based on iron oxide nanoparticles

Area of Science:

• Nanotechnology
• Biomedical Imaging
• Materials Science

Background:

• Development of activatable probes for enhanced tumor visualization.
• Need for dual-modality imaging agents combining fluorescence and MRI.
• Role of matrix metalloproteinases (MMPs) in tumor progression.

Purpose of the Study:

• To fabricate and characterize Cy5.5-MMP substrate and PEG conjugated iron oxide nanoparticles with thin silica coating (PCM-CS).
• To evaluate PCM-CS as an activatable dual imaging probe for tumor detection using NIRF and MRI.
• To assess the probe's sensitivity and specificity towards MMP-2 activity in vitro and in vivo.

Main Methods:

• Synthesis and characterization of PCM-CS nanoparticles using dynamic light scattering.
• In vitro evaluation of fluorescence quenching and recovery upon MMP-2 cleavage.
• In vivo tumor imaging in mice using near-infrared fluorescence (NIRF) and magnetic resonance imaging (MRI) after intravenous injection of PCM-CS.

Main Results:

• PCM-CS nanoparticles exhibited stable size (43.1 ± 6.3 nm) without aggregation.
• High fluorescence quenching efficiency (97.2%) with specific recovery upon MMP-2 cleavage at low enzyme concentrations (≤0.5 nM).
• Successful in vivo visualization of tumors via NIRF and MRI, with enhanced tumor-to-normal tissue contrast (3-4x for NIRF, 34% for MRI) and reduced signal in inhibitor-treated tumors.

Conclusions:

• PCM-CS serves as an effective activatable dual imaging probe for tumor detection.
• The probe demonstrates high sensitivity and specificity for MMP-2, enabling targeted tumor visualization.
• Dual-modality imaging with PCM-CS offers improved tumor detection and characterization capabilities.