Visualising sub-second dynamics of nanoparticle extravasation in vivo

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Vascular Biology

Background:

• Altered vascular integrity is a key indicator in various diseases.
• Monitoring vascular permeability is crucial for understanding disease mechanisms and developing new treatments.
• Current methods for assessing vascular permeability have limitations in sensitivity and specificity.

Purpose of the Study:

• To develop a novel real-time fluorescence imaging technique for visualizing and quantifying vascular permeability in vivo.
• To differentiate between transcellular and paracellular transport pathways.
• To evaluate the blood-brain barrier (BBB) integrity and test a nanoparticle-based strategy for BBB perturbation.

Main Methods:

• Utilized lanthanide-based upconversion nanoparticles as contrast agents for fluorescence imaging.
• Employed simultaneous confocal imaging of vasculature and single particle tracking at video rate.
• Conducted high-throughput surveillance in live zebrafish larvae to detect nanoparticle extravasation.

Main Results:

• Achieved superior sensitivity and specificity in visualizing vascular permeability compared to conventional fluorescent dyes.
• Distinguished between transcellular and paracellular transport based on sub-second dynamics of nanoparticle extravasation.
• Demonstrated a 36.5-fold increase in BBB penetration using polysorbate-functionalized nanoparticles, indicating enhanced transcellular crossing.

Conclusions:

• The developed imaging technique enables precise, real-time monitoring of vascular integrity and endothelial transport.
• This method offers a powerful tool for advancing research in vascular biology, disease diagnostics, and drug delivery.
• Functionalized nanoparticles show promise for targeted drug delivery across biological barriers like the BBB.