Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

Abstract

Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named 'eruptions') into the tumour interstitial space. We propose that 'dynamic vents' form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.

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“…Nonetheless, alleviating the systemic toxicity of anticancer cabazitaxel agent facilitated the dose intensification and thereby improved efficacy. On the other hand, we can expect that once accumulated within cancerous tissues via the enhanced permeability and retention (EPR) effect (47)(48)(49), the pSNM scaffold may prolong the exposure of tumor cells to cabazitaxel at therapeutically relevant concentrations.…”

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“…pressure gradient [49]. Both 30 nm-sized and 70 nm-sized nanoparticles were erupted into tumor interstitial spaces.…”

“…Both 30 nm-sized and 70 nm-sized nanoparticles were erupted into tumor interstitial spaces. The 30 nm-sized nanoparticle quickly diffused away but the 70 nm-sized nanoparticle was trapped in stroma-rich barriers [49]. Cancer cells mostly surround blood vessels in some clinical tumor (e.g.…”

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