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Gold nanoparticles for the treatment of glucocorticoid insensitive asthma: what we have learned so far?

Abstract: Asthma is a chronic pulmonary disease that affects millions of people globally and can be fatal. 55% of asthmatics have inadequate control of their symptoms despite recognized advances in currently available therapy. Current guidelines recommend clinicians to treat asthma patients regularly with low doses of inhaled glucocorticoids (GCs), the most effective asthma therapy available. Still, about 10% of patients require the maximal inhaled GC dose or elevated doses of oral GCs, which leads to substantial adverse effects. Moreover, approximately 1% of asthma patients are entirely GC insensitive, prompting the search for novel anti-inflammatory treatments.   The clinical application of gold metallic compounds and their complexes for treating inflammation-related diseases has several thousand years of history, but some side effects limit its use. It is well established that biologically active molecules formulated as nanoparticles can improve the bioavailability of drugs and reduce their toxicity. Gold nanoparticles possess significant anti-inflammatory and anti-oxidative properties and is associated with therapeutic effects on several chronic diseases, including asthma. Whether gold nanoparticles can interfere with GC insensitive asthma is unclear. Using a murine model of asthma, we provide evidence that nebulized gold nanoparticles can inhibit GC resistant asthma in a mechanism related to reduction of oxidative stress and rescue of HDAC2 levels. The data also point out that stimulation of anti-oxidative response through activation of Nrf2 may be an essential part of the interventional effect of gold nanoparticles on difficult-to-treat asthma.

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