The pathways for nanoparticle transport across tumour endothelium

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Biology

Background:

• The enhanced permeability and retention (EPR) effect is a widely accepted model for nanoparticle tumor delivery.
• However, the active transport and retention principle offers an alternative explanation for nanoparticle accumulation in tumors.
• The precise mechanism by which nanoparticles traverse tumor endothelial cells remains unclear.

Purpose of the Study:

• To elucidate the primary pathway utilized by nanoparticles to cross tumor endothelial cells.
• To investigate the role of membrane ruffles and endocytosis in nanoparticle transport across the tumor endothelium.
• To understand how nanoparticle size influences the contribution of different transport pathways.

Main Methods:

• Utilized advanced microscopy techniques to observe nanoparticle-endothelial cell interactions in vivo and in vitro.
• Investigated the role of macropinocytosis and receptor-mediated endocytosis in nanoparticle internalization.
• Analyzed the effect of nanoparticle size on the efficiency of different transport pathways.

Main Results:

• Demonstrated that nanoparticles predominantly cross tumor endothelial cells via non-receptor-based macropinocytosis.
• Identified tumor endothelial cell membrane ruffles as key structures for capturing and internalizing nanoparticles.
• Observed that nanoparticle size significantly impacts the contribution of macropinocytosis versus clathrin-mediated endocytosis.
• Found higher membrane ruffle density in tumor endothelium compared to healthy endothelium.

Conclusions:

• Macropinocytosis is the principal mechanism for nanoparticle transport across tumor endothelial cells.
• Tumor endothelial cell membrane ruffles play a critical role in nanoparticle uptake and subsequent release into the tumor interstitium.
• Understanding these transport mechanisms is essential for optimizing nanoparticle-based cancer therapies and drug delivery systems.