Neutrophil-mediated Transport of Nanoparticles across Blood Barriers Zhenjia Wang and Dafeng Chu Department of Pharmaceutical Sciences College of Pharmacy, Washington State University, WA, USA ABSTRACT: Inflammation disorders are underlying components of most diseases and exist in extravascular tissues. Intravenous administration of therapeutic nanoparticles rarely reach the diseased sites due to a blood-vessel barrier. Here we report the development of a novel strategy to deliver therapeutic nanoparticles across this blood vessel barrier via the neutrophil transmigration pathway. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously infused nanoparticles made from denatured albumin were specifically internalized by activated neutrophils, and subsequently the neutrophils migrated across blood vessels and deposited nanoparticles into inflammatory tissues. Furthermore, nanoparticle internalization did not affect neutrophil mobility and functions. Using albumin nanoparticles we were able to deliver anti-inflammatory drugs or antibiotics to inflammatory or infected lungs, dramatically mitigating the lung inflammation induced by LPS (lipopolysaccharide) or infection by P. aeruginosa bacteria. Our results illustrate that neutrophils can be exploited as novel vehicles to mediate the transport of therapeutic nanoparticles across blood vessel barrier, and using this approach we could significantly improve current treatments of acute inflammatory diseases and infection.

Neutrophil-mediated transport of nanoparticles across blood barriers

251st National Meeting (2016)

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