ABSTRACT
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 framework (MOF) (i.e. MIL-100(Fe)) and glutathionate protected gold nanoclusters (i.e. Au25SG18 NCs). This nano-carrier exhibits low toxicity and excellent colloidal stability combined with the high loading capacity of the glucocorticoid dexamethasone phosphate (DexP) whose pH-dependent delivery was observed. The drug loaded Au@MIL nanocarrier shows high anti-inflammatory activity due to its capacity to specifically hinder inflammatory cell growth, scavenge intracellular reactive oxygen species (ROS) and downregulate pro-inflammatory cytokine 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 a new avenue for the nanotherapy of inflammatory diseases but also enhances our fundamental knowledge of the role of nanoMOF based nanomedicine in the regulation of innate immune signaling.
Subject(s)
Anti-Inflammatory Agents , Dexamethasone , Gold , Inflammation , Metal Nanoparticles , Metal-Organic Frameworks , Signal Transduction , Toll-Like Receptors , Gold/chemistry , Mice , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Signal Transduction/drug effects , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Animals , Toll-Like Receptors/metabolism , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Inflammation/drug therapy , Dexamethasone/chemistry , Dexamethasone/pharmacology , Reactive Oxygen Species/metabolism , RAW 264.7 Cells , Drug Carriers/chemistry , Humans , NF-kappa B/metabolismABSTRACT
[This corrects the article DOI: 10.3389/fimmu.2024.1355845.].
ABSTRACT
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a dysfunction of the immune system. Mesenchymal stromal cell (MSCs) derived extracellular vesicles (EVs) are nanometer-sized particles carrying a diverse range of bioactive molecules, such as proteins, miRNAs, and lipids. Despite the methodological disparities, recent works on MSC-EVs have highlighted their broad immunosuppressive effect, thus driving forwards the potential of MSC-EVs in the treatment of chronic diseases. Nonetheless, their mechanism of action is still unclear, and better understanding is needed for clinical application. Therefore, we describe in this review the diverse range of bioactive molecules mediating their immunomodulatory effect, the techniques and possibilities for enhancing their immune activity, and finally the potential application to SLE.