Gold nanoclusters/MIL-100(Fe) bimodal nanovector for the therapy of inflammatory disease through attenuation of Toll-like receptor signaling.

A better understanding of the molecular and cellular events involved in the inflammation process has opened novel perspectives in the treatment of inflammatory diseases, particularly through the development of well-designed nanomedicines. Here we describe the design of a novel class of anti-inflammatory nanomedicine (denoted as Au@MIL) synthesized through a one-pot, cost-effective and green approach by coupling a benchmark mesoporous iron(III) carboxylate Metal Organic Frameworks (MOF) (i.e. MIL-100(Fe)) and glutathionate protected gold nanoclusters (i.e. Au25SG18 NCs). This nano-carrier exhibits a low toxicity and excellent colloidal stability combined with high loading capacity of the glucocorticoid dexamethasone phosphate (DexP) whose pH-dependent delivery was observed. The drug loaded Au@MIL nanocarrier has shown high anti-inflammatory activity due to its capacity to specifically hinder the inflammatory cells growth, scavenge intracellular reactive oxygen species (ROS) and downregulate pro-inflammatory cytokines secretion. In addition, this formulation has the capacity to inhibit the Toll-like receptor (TLR) signaling cascade namely the nuclear factor kappa B (NF-κB) and the interferon regulatory factor (IRF) pathways. This not only provides new avenue for nanotherapy of inflammatory diseases but enhances our fundamental knowledge of the role of nanoMOF based nanomedicine in the regulation of innate immune signaling