Polymerized Salicylic Acid Microparticles Reduce the Progression and Formation of Human Neutrophil Extracellular Traps (NET)s

Polymeric particles are an innovative solution to treating inflammatory diseases that currently lack adequate clinical therapies. Using a high-throughput in vitro NETosis model, interactions between particles and neutrophils are thoroughly examined, and particle-based therapeutics can be optimized. The findings suggest polymerized salicylic acid (Poly-SA) microparticles reduce neutrophil inflammatory function, inhibiting NETosis through suppression of stress-activated protein kinases.

Abstract

Neutrophils can contribute to inflammatory disease propagation via innate mechanisms intended for inflammation resolution. For example, neutrophil extracellular traps (NETs) are necessary for trapping pathogens but can contribute to clot formation and blood flow restriction, that is, ischemia. Currently, no therapeutics in the clinic directly target NETs despite the known involvement of NETs contributing to mortality and increased disease severity. Vascular-deployed particle-based therapeutics are a novel and robust alternative to traditional small-molecule drugs by enhancing drug delivery to cells of interest. This work designs a high-throughput assay to investigate the immunomodulatory behavior and functionality of salicylic acid-based polymer-based particle therapeutics against NETosis in human neutrophils. Briefly, this work finds that polymeric composition plays a role, and particle size can also influence rates of NETosis. Salicylate-based polymeric (Poly-SA) particles are found to functionally inhibit NETosis depending on the particle size and concentration exposed to neutrophils. This work demonstrates the high throughput method can help fast-track particle-based therapeutic optimization and design, more efficiently preparing this innovative therapeutics for the clinic.