Multifunctional endogenous small molecule-derived polymer composite nanoparticles for the treatment of acute sepsis therapy

Abstract

The complex and rapidly progressing nature of sepsis calls for the development of multifunctional and rapid-acting therapeutic agents, instead of single-modal treatments. To address this challenge, a biodegradable, easily synthesized, and antibiotic-free multifunctional nanoparticle has been created for sepsis therapy. The nanoparticle was formed by the electrostatic interaction between two endogenous small molecule-derived polymers, poly(lipoic acid) and poly-lysine, and possessed various functions such as antibacterial activity, adsorption of cell-free DNA, scavenging of reactive oxygen and nitrogen species, providing a comprehensive approach to combating sepsis. Treatment using the cecal ligation and puncture (CLP) model confirmed the therapeutic benefits of the nanoparticles, demonstrating reduced levels of reactive oxygen across multiple organs, diminished levels of M1 proinflammatory macrophages, and elevated levels of M2 anti-inflammatory macrophages post-treatment. These findings emphasized the effectiveness of the nanoparticles in sepsis therapy, and properties of degradation, easy preparation, and swift therapeutic response made them promising for the future clinical applications.