Neutrophil extracellular traps: Formation, pathological roles, and nanoparticle-based therapeutic targeting strategies

Abstract

Neutrophil extracellular traps (NETs) are large, web-like DNA structures released by neutrophils, coated with histones and antimicrobial proteins. They serve as a crucial defense mechanism for neutrophils against microbial invasion, playing a significant role in eliminating microorganisms such as bacteria, fungi, and viruses. While NETs are primarily recognized for their role in microbial defense, growing evidence indicates that excessive NET formation, triggered by physical and chemical stimuli, pathogens, or pathological factors, can worsen inflammation and cause organ damage. Understanding NETs' presence in various tissues and body fluids is crucial for elucidating their contribution to disease etiopathogenesis. By designing nanoparticles that can either prevent NET formation or facilitate their degradation, researchers aim to mitigate the harmful effects of excessive NETs. These nanotechnological interventions can be tailored to specifically target the molecular components of NETs, enhancing treatment precision and efficacy. Furthermore, nanoparticles can deliver therapeutic agents directly to inflammation sites, reducing systemic side effects and improving patient outcomes. This review summarizes the role of NETs in various pathologies, focusing on strategies to inhibit NETosis, including mechanisms of pathogen evasion, and the use of nanodelivery systems to enhance the efficiency of NETs inhibition or removal.

Keywords: COVID19; DNase I; Drug delivery systems; Infectious diseases; NETosis; NETs; Neutrophils.