Enhanced Permeability and Retention-like Extravasation of Nanoparticles from the Vasculature into Tuberculosis Granulomas in Zebrafish and Mouse Models
| Autor: | Simon Van Herck, Bruno G. De Geest, Federico Fenaroli, Kerstin Johann, Shahla Bagherifam, David G. Russell, Urska Repnik, Dominik M. Frei, Frode Miltzov Skjeldal, Gareth Griffiths, Yitian Xu, Agnese Kocere, Rainer Haag, Matthias Barz, Pradip Dey |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
inorganic chemicals
Endothelium General Physics and Astronomy 02 engineering and technology Pulmonary Artery 010402 general chemistry 01 natural sciences Permeability law.invention Mice Confocal microscopy law medicine Animals General Materials Science Zebrafish Tuberculosis Pulmonary Mycobacterium marinum Liposome Granuloma Microscopy Confocal biology Chemistry General Engineering technology industry and agriculture 021001 nanoscience & nanotechnology biology.organism_classification Extravasation 0104 chemical sciences Disease Models Animal medicine.anatomical_structure Permeability (electromagnetism) Drug delivery Biophysics Nanoparticles 0210 nano-technology |
| Popis: | The enhanced permeability and retention (EPR) effect is the only described mechanism enabling nanoparticles (NPs) flowing in blood to reach tumors by a passive targeting mechanism. Here, using the transparent zebrafish model infected with Mycobacterium marinum we show that an EPR-like process also occurs allowing different types of NPs to extravasate from the vasculature to reach granulomas that assemble during tuberculosis (TB) infection. PEGylated liposomes and other NP types cross endothelial barriers near infection sites within minutes after injection and accumulate close to granulomas. Although similar to 100 and 190 nm NPs concentrated most in granulomas, even similar to 700 nm liposomes reached these infection sites in significant numbers. We show by confocal microscopy that NPs can concentrate in small aggregates in foci on the luminal side of the endothelium adjacent to the granulomas. These spots are connected to larger foci of NPs on the ablumenal side of these blood vessels. EM analysis suggests that NPs cross the endothelium via the paracellular route. PEGylated NPs also accumulated efficiently in granulomas in a mouse model of TB infection with Mycobacterium tuberculosis, arguing that the zebrafish embryo model can be used to predict NP behavior in mammalian hosts. In earlier studies we and others showed that uptake of NPs by macrophages that are attracted to infection foci is one pathway for NPs to reach TB granulomas. This study reveals that when NPs are designed to avoid macrophage uptake, they can also efficiently target granulomas via an alternative mechanism that resembles EPR. |
| Databáze: | OpenAIRE |
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