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Nanoparticles as ‘Trojan horses’ to tackle inflammatory disease
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A new study has described how albumin nanoparticles loaded with an anti-inflammatory drug can be targeted to neutrophils which cause injury by building up at the site of injury while sparing circulating neutrophils. The study from the University of Illinois in Chicago was published online in Nature Nanotechnology on February 23rd. The study could point the way forward to resolve the problem of targeting anti-inflammatory medication effectively to the cells causing damage while allowing other immune cells to remain in circulation to come into play when needed.

Neutrophils are circulating granulocytic cells that accumulate in response to signals at the site of infection and/or injury. When there, they engulf microbes and debris in a process known as phagocytosis, as well as releasing mediators that can help resolve the infection and promote healing. However, in some cases neutrophils can have a damaging effect, for example in chronic and acute inflammatory disease conditions. In these cases, neutrophils can accumulate at the blood vessel wall, sticking both to each other and the endothelium. This can be problematic particularly in some respiratory conditions, for example in the case of acute lung injury when it can lead to severe breathing difficulties and can be fatal if ineffectively treated.

Nanoparticles have risen in prominence in recent years as a way to target therapies in a variety of conditions including some cancers. In this case, the researchers exploited the fact that adhesive neutrophils express cell surface Fcɣ receptors which circulating neutrophils lack or express at a much reduced level. The researchers used a mouse model treated with an inflammatory cytokine called tumour necrosis factor to induce vascular inflammation. The albumin nanoparticles in the study could adhere to the Fcɣ receptors, targeting them to the adherent neutrophils and they were labelled with a fluorescent dye so their location could be studied in real time. The nanoparticles were loaded with an anti-inflammatory tyrosine kinase inhibitor called piceatannol. When delivered to the adherent neutrophils, this drug interfered with the integrin-mediated adhesive signalling pathways inside the neutrophils, causing them to become detached and released into the circulation.

Dr Asrar Malik, senior author on the paper, is confident that this type of nanoparticle technology can improve therapy in inflammatory diseases, which is currently reliant on corticosteroids and non-steroidal anti-inflammatory drugs. These are unselective, broad-range drugs with significant side-effects. Dr Malik concluded: "The nanoparticle is very much like a Trojan horse….It binds to a receptor found only on these activated, sticky neutrophils, and the cell automatically engulfs whatever binds there. Because circulating neutrophils lack these receptors, the system is incredibly precise and targets only those immune cells that are actively contributing to inflammatory disease."

Sources:

Wang,Z., Li, J., Cho, J. and Malik, A.B., 2014. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils. Nature Nanotechnology (2014); doi:10.1038/nnano.2014.17

Press release from University of Illinois; available from: http://www.eurekalert.org/pub_releases/2...022114.php [Accessed 24 February 2014].
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