Journal: International Journal of Nanomedicine
Article Title: Advancements, Challenges, and Future Prospects of Nanotechnology in Sepsis Therapy
doi: 10.2147/IJN.S488026
Figure Lengend Snippet: ( A ) Interaction of nanoparticles (NPs) with macrophages and the regulation of macrophage pro/anti-inflammatory functions by NPs. (I) Upon entering the body, NPs bind to plasma proteins and are internalized by macrophages. NPs are endocytosed into endosomes, degraded, and then released extracellularly to exert their active effects; other endosomes fuse with lysosomes to form endolysosomes, exerting intracellular effects. (II) First, NPs can eliminate macrophage activation by phagocytosis and restriction of pathogen-associated molecular patterns (PAMPs); second, they inhibit the interaction between PAMPs and pattern recognition receptors (PRRs); third, NPs that enter the cytoplasm inhibit the transmission of inflammatory signaling pathways; finally, NPs inhibit the release of active products from inflammatory pathways, controlling cell and tissue damage caused by overactivated macrophages. (III) NPs modulate the pro-inflammatory activity of macrophages. NPs can enhance PRR activation to initiate macrophage inflammatory responses. Once in the cytoplasm, NPs activate downstream pathways and inflammasomes to induce the production of pro-inflammatory factors. NPs, nanoparticles; PAMPs, pathogen-associated molecular patterns; ROS, reactive oxygen species; ILs, interleukins; TNFs, tumor necrosis factors; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor-κB. ( B ) Regulation of macrophage polarization by nanoparticles (NPs). M1-type macrophages typically function during the cytokine storm phase of sepsis, releasing large amounts of pro-inflammatory mediators, including reactive oxygen species (ROS), interferons (IFNs), interleukins (ILs), and tumor necrosis factors (TNFs). In contrast, M2-type macrophages usually appear during the immune paralysis phase, secreting anti-inflammatory mediators, most notably IL-10. During excessive inflammatory stimulation, the continuous release of pro-inflammatory mediators by M1-type macrophages causes damage to the body, whereas, during immune paralysis, excessive activation of M2-type macrophages increases the risk of secondary infections. NPs can modulate macrophage polarization at different stages of sepsis to improve prognosis. NPs, nanoparticles; ROS, reactive oxygen species; ILs, interleukins; IFNs, interferons; TNFs, tumor necrosis factors. ( C ) Interference of macrophage pyroptosis by nanoparticles (NPs). NPs can block the activation of caspase-1 and caspase-4/5/11, reducing the release of DAMPs (damage-associated molecular patterns) and preventing unnecessary tissue and cell damage. NPs, nanoparticles; LPS, lipopolysaccharide; IL-1b, interleukin-1b; DAMPs, damage-associated molecular patterns; GSDMD, gasdermin D. Reproduced from Song C, Xu J, Gao C, Zhang W, Fang X, Shang Y. Nanomaterials targeting macrophages in sepsis: a promising approach for sepsis management. Front Immunol. 2022;13:1026173. Copyright © 2022 Song, Xu, Gao, Zhang, Fang and Shang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Article Snippet: © 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. ( C ) γ3 peptide grafted onto nanoparticle (NP) surfaces enhances uptake by activated endothelial cells (ECs) and specifically targets the lungs to alleviate inflammation.
Techniques: Clinical Proteomics, Activation Assay, Transmission Assay, Protein-Protein interactions, Activity Assay, Blocking Assay