Dual-Functional Cerium Oxide Nanoparticles with Antioxidant and DNase I activities to Prevent and degrade Neutrophil Extracellular Traps

TL;DR

This study develops cerium oxide nanoparticles conjugated with DNase I that can both prevent NET formation by reducing ROS and degrade existing NETs, offering a potential therapy for thrombotic diseases.

Contribution

The paper introduces a novel dual-functional nanoparticle combining antioxidant and DNase I activities to target and mitigate neutrophil extracellular traps.

Findings

CNPs reduce intracellular ROS and inhibit NET formation.

DNase I-functionalized CNPs degrade pre-formed NETs.

Nanoparticles are efficiently internalized by neutrophils.

Abstract

Neutrophils play a central role in immunothrombosis through the formation of neutrophil extracellular traps (NETs), a process known as NETosis. Upon stimulation, neutrophils release decondensed chromatin structures enriched with proteolytic enzymes, which contribute to thrombus formation. NETosis is critically dependent on reactive oxygen species (ROS), making redox regulation a key point of intervention. The intrinsic redox cycling of cerium oxide nanoparticles (CNPs) imparts self-regenerating antioxidant properties suitable for modulating neutrophil-driven oxidative stress. To address both the prevention and clearance of NETs, we developed dual-functional CNPs conjugated with DNase I. These engineered nanoparticles were efficiently internalized by neutrophils, reduced intracellular ROS levels, and inhibited NETs formation. In addition, DNase I-functionalized CNPs degraded pre-formed NETs. This dual-action strategy offers a promising nanotherapeutic platform for mitigating NETs-associated thrombotic pathologies. Ongoing studies aim to enhance thrombus targeting and assess in vivo efficacy.