Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment

by Selleckchem | Oct 27 2023

Background: Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management.

Results: Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time.

Conclusions: Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.

Comments:

The study described the successful development of a novel nanometer drug loading system, called FZ/MER-AgMOF@Bm, for the management of sepsis. Sepsis is a condition characterized by infection-induced physiological, pathological, and biochemical abnormalities, often leading to multiple organ dysfunction. While the mortality rate associated with sepsis has decreased, many survivors still experience persistent infection, emphasizing the need for new treatment approaches.

The researchers used nanoparticles that were modified with the membrane of bone marrow mesenchymal stem cells (BMSCs) treated with lipopolysaccharide (LPS). These nanoparticles served as a delivery system for two drugs: FPS-ZM1, which has anti-inflammatory properties, and meropenem, a broad-spectrum antibiotic. The nanocore of the nanoparticles was made of silver metal organic framework (AgMOF), which allowed for the loading of the drugs.

The FZ/MER-AgMOF@Bm nanoparticles were designed to specifically target infectious microenvironments (IMEs) in the body, where they exerted dual anti-inflammatory and antibacterial effects. The nanoparticles effectively reduced the excessive inflammatory response and eliminated bacteria. Furthermore, they promoted the polarization of macrophages to the M2 phenotype, which is associated with anti-inflammatory properties.

In an experimental model of sepsis induced by cecal ligation and puncture (CLP) in mice, the treatment with FZ/MER-AgMOF@Bm nanoparticles resulted in several beneficial effects. It reduced the levels of pro-inflammatory factors, mitigated lung injury, improved hypothermia caused by septic shock, and prolonged the survival time of the mice.

Overall, the study demonstrated that the developed nanoparticles with combined anti-inflammatory and antimicrobial properties have the potential to be a new and promising strategy for the management of sepsis. By alleviating the cytokine storm and protecting vital organ functions, these nanoparticles offer a multifaceted approach to sepsis treatment. However, further research and clinical trials are needed to validate and translate these findings into practical applications for human sepsis management.