Research team from The Seventh Affiliated Hospital, Sun Yat-sen University reports: Ce-myricetin nanoparticles alleviate inflammation and multi-organ damage through ROS clearance and macrophage reprogramming in sepsis

Background

Sepsis is a life-threatening syndrome triggered by infection, leading to inflammatory dysregulation, cellular and organ damage, and potentially multiple organ failure. Current clinical management relies on antibiotics and supportive care, which often fail to precisely modulate the dysregulated immune response or effectively improve long-term outcomes.

In the pathological mechanism of sepsis, excessive generation of reactive oxygen species (ROS) is closely linked to the amplification of inflammatory cascades. ROS can activate the TLR4-MyD88-NF-κB signaling pathway, resulting in the overproduction of inflammatory cytokines such as IL-1β, IL-6, and TNF-α, and triggering a "cytokine storm." Concurrently, the imbalance in macrophage polarization toward the pro-inflammatory M1 phenotype over the reparative M2 phenotype further exacerbates inflammatory injury. Therefore, developing therapeutic strategies capable of scavenging ROS and regulating macrophage phenotype is of great significance for sepsis treatment. Natural polyphenols like myricetin possess antioxidant and anti-inflammatory potential but are limited by poor stability and bioavailability. The rare earth element cerium (Ce), with its reversible Ce³⁺/Ce⁴⁺ redox cycle, can enhance ROS scavenging capability. Integrating both into functional nanoparticles offers a promising approach for synergistic therapy.

Achievement Summary

This study developed Ce-Myr nanoparticles constructed from cerium ions and myricetin. The nanoparticles demonstrated structural stability, good dispersibility, and potent ROS scavenging ability. In vitro, the material significantly reduced oxidative stress, protected mitochondrial function, and modulated the immune state of macrophages by suppressing pro-inflammatory M1 polarization and promoting reparative M2 polarization. In a mouse model of sepsis, Ce-Myr nanoparticles markedly improved survival rates, alleviated multi-organ injury, and reduced serum levels of inflammatory cytokines and biochemical injury markers. Mechanistic studies revealed that the material achieves combined therapeutic effects of "antioxidant + immune reprogramming" by inhibiting the activation of the TLR4-MyD88-NF-κB pathway. This strategy provides a novel nano-platform with translational potential for sepsis treatment.

Research Team Introduction

This research was completed by the team led by Associate Researcher Kang Yang at The Seventh Affiliated Hospital of Sun Yat-sen University. Their main research focuses include nanomaterials and their applications in inflammation and sepsis, immune regulation mechanisms, and therapeutic strategies for ROS-related diseases. The team's work has been supported by several research grants, including: Shenzhen Science and Technology Program (No. RCYX20200714114645131 and No. JCYJ20230807110421045), Guangdong Basic and Applied Basic Research Foundation (No. 2024A151503014), and the Scientific Research Start-up Fund of The Seventh Affiliated Hospital, Sun Yat-sen University (No. ZSQYBRJH0011). The team is dedicated to ongoing research in nanomedicine, inflammation regulation, and the prevention and treatment of multi-organ injury.

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.