Manipulating dynamic tumor vessel permeability to enhance polymeric micelle accumulation

Selectively delivering anticancer drugs to solid tumors while avoiding their accumulation in healthy tissues is a major goal polymeric micelle research. We have recently discovered that the extravasation and permeation of micelles occur dynamic manner characterized by vascular bursts followed brief vigorous outward flow fluid (called “nano-eruptions”). Nano-eruptions allow delivery micelle-associated drugs, though can be heterogeneous both among within an individual tumor, leading suboptimal intratumoral distribution. Manipulation nano-eruptions expected improve efficiency drug systems (DDSs). By using compounds affect environment, i.e. TGF-β inhibitor chloroquine, possibility manipulating was investigated. Both were tested mouse xenograft model GFP-labeled pancreatic tumor cells tracing nano-eruption events size-modulated real-time through intravital confocal laser scanning microscopy. The increased number vents, extended duration time, generated vents with wide range sizes. Chloroquine did not frequency nano-eruptions, but it vessel diameter, maximum area, radial increase. chloroquine augmented diffuse stroma, these medications had greater effect on larger size, 70-nm, than smaller having 30-nm diameter. results indicate inhibition refashion distribution DDSs different mechanisms.