Nanomaterials targeting macrophages in sepsis: A promising approach for sepsis management

Abstract

Sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. Macrophages play significant roles in host against pathogens and the immunopathogenesis of sepsis, such as phagocytosis of pathogens, secretion of cytokines, and phenotype reprogramming. However, the rapid progression of sepsis impairs macrophage function, and conventional antimicrobial and supportive treatment are not sufficient to restore dysregulated macrophages roles. Nanoparticles own unique physicochemical properties, surface functions, localized surface plasmon resonance phenomenon, passive targeting in vivo, good biocompatibility and biodegradability, are accessible for biomedical applications. Once into the body, NPs are recognized by host immune system. Macrophages are phagocytes in innate immunity dedicated to the recognition of foreign substances, including nanoparticles, with which an immune response subsequently occurs. Various design strategies, such as surface functionalization, have been implemented to manipulate the recognition of nanoparticles by monocytes/macrophages, and engulfed by them to regulate their function in sepsis, compensating for the shortcomings of sepsis traditional methods. The review summarizes the mechanism of nanomaterials targeting macrophages and recent advances in nanomedicine targeting macrophages in sepsis, which provides good insight for exploring macrophage-based nano-management in sepsis.

Polymeric Particle BAM15 Targeting Macrophages Attenuates the Severity of LPS-Induced Sepsis: A Proof of Concept for Specific Immune Cell-Targeted Therapy

“…Here, BAM15, at a high dose of free-form or BAM15 particles, was not toxic to the mice ( Figure 7 ). Regarding the selective blockage only in macrophages, our particles might be an additional strategy to the conditional gene deletion (LyM-Cre) [ 24 , 32 ] and nanoparticle [ 25 , 26 ] strategies that have been previously described. With our previous protocol [ 20 ], PLGA particles were selectively delivered to macrophages but not DCs ( Figure 6 ), and BAM15 particles had neutralizing effects on LPS-induced inflammation only in macrophages but not neutrophils ( Figure 5 ).…”

“…The mortality rate for sepsis remains high, despite improved supportive treatment, which is partly due to the hyper-responses to microbial molecules of several immune cells, especially macrophages [ 23 ]. Indeed, the immunological blockage on macrophages using LysM-Cre mice [ 24 ] and nanomaterials targeting macrophages successfully attenuates hyper-inflammation in sepsis [ 25 , 26 ]. Here, several tests were performed to assess (i) the impacts of BAM15 on lipopolysaccharide (LPS)-induced M1 polarization or M2 polarization (using IL-4 and cancer cell supernatant) and (ii) the influence of BAM15-PLGA particles (BAM15 particles) on macrophages and in mice.…”

Developments and Trends of Nanotechnology Application in Sepsis: A Comprehensive Review Based on Knowledge Visualization Analysis

“…The study of macrophage functions, central to host defense and inflammation, is integral to understanding and leveraging the immunomodulatory capabilities of NPs, offering enormous benefits to transform sepsis treatment strategies. 109,110 Nanoplatforms Targeting Toxins and Pathogenic Elements in Sepsis. In the battle against sepsis, certain NPs have been designed to seek out and neutralize critical toxin and pathogenic constituents, including cfDNA, extracellular histones, ROS and inflammatory neutrophil.…”

“…These studies bring another option to the treatment of sepsis, particularly in restoring immune function in sepsis patients. The study of macrophage functions, central to host defense and inflammation, is integral to understanding and leveraging the immunomodulatory capabilities of NPs, offering enormous benefits to transform sepsis treatment strategies. , …”

Novel therapeutic role of Ganoderma Polysaccharides in a septic mouse model - The key role of macrophages

“…Macrophages, often hailed as the immune system's stalwarts, are instrumental during the initial stages of most infections. However, their role in sepsis can be ambivalent, at times intensifying the inflammatory cascade rather than curbing it [ 6 , 7 ]. T cells, with a special emphasis on regulatory T cells (Treg), are paramount in striking a harmonious balance between pro-inflammatory and anti-inflammatory actions.…”