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Biomolecular Imaging of Cellular Uptake of Nanoparticles using Multimodal Nonlinear Optical Microscopy
Published on: May 16, 2022
Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle
Kimberly A Kelly1, Jennifer R Allport, Andrew Tsourkas
1Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Circulation Research
|January 18, 2005
Summary
Novel nanoparticles targeting vascular adhesion molecule-1 (VCAM-1) enable enhanced in vivo imaging. This VCAM-1 targeting strategy improves imaging agent delivery and visualization of inflammatory and atherosclerotic conditions.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Nanotechnology
Background:
- Vascular adhesion molecule-1 (VCAM-1) is crucial in leukocyte adhesion and a key target for imaging and therapy.
- Developing targeted imaging agents for VCAM-1 is essential for visualizing inflammatory and vascular diseases.
- Phage display and nanoparticle technology offer promising avenues for targeted molecular imaging.
Purpose of the Study:
- To develop novel VCAM-1-targeted imaging agents using phage display peptides and multimodal nanoparticles.
- To investigate VCAM-1-mediated cell internalization as an amplification strategy for improved imaging.
- To assess the efficacy of these agents for in vivo MRI and fluorescence imaging of VCAM-1 expression.
Main Methods:
- Iterative phage display on murine endothelium under flow to identify VCAM-1-binding peptides.
- Selection of a peptide with the VHSPNKK motif, homologous to VLA-4, a VCAM-1 ligand.
- Conjugation of the selected peptide to magnetofluorescent nanoparticles (VNPs) for multimodal imaging.
Main Results:
- The VHSPNKK peptide demonstrated high affinity for VCAM-1 and blocked leukocyte-endothelial interactions, outperforming a VCAM-1 antibody in target-to-background ratios.
- VHSPNKK-modified VNPs selectively targeted VCAM-1-expressing endothelial cells but not macrophages.
- In vivo studies successfully visualized VCAM-1-expressing endothelial cells in inflammatory and atherosclerotic mouse models.
Conclusions:
- Small peptide sequences can effectively modify nanoparticle targeting capabilities.
- VCAM-1-mediated cell internalization serves as an effective amplification strategy, enhancing target-to-background ratios.
- This peptide-nanoparticle technology is a valuable tool for in vivo imaging of endothelial markers in disease states.
