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

Abstract

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.

Combination Therapy with Resveratrol and Celastrol Using Folic Acid‐Functionalized Exosomes Enhances the Therapeutic Efficacy of Sepsis

“…As reported by Ye et al. [ 8 ] and Lu et al., [ 37 ] nanoparticles injected via tail vein could accumulate in septic mice lungs, likely due to endothelial damage and the resultant hyperpermeability. Therefore, the increase of lung permeability induced Exo‐based nanocarriers to the lungs and lead to accumulation.…”

Developments and Trends of Nanotechnology Application in Sepsis: A Comprehensive Review Based on Knowledge Visualization Analysis

“…(G) Schematic diagram of experimental design for sepsis therapy and Kaplan–Meier survival charts for each treatment group (control n = 4, other treatment groups n = 8). Reprinted (Adapted or Reprinted in part) with permission under a Creative Commons Attribution 4.0 International License from ref . Copyright 2023, Springer Nature.…”

“…(D) TEM images of AgMOF, LPS-BMSC membrane vesicles (BMSCm) and AgMOF@Bm and Cumulative release rate of FPS-ZM1 and Meropenem from FZ/MER-AgMOF@Bm at pH 6.5 or pH 7.4. Reprinted (Adapted or Reprinted in part) with permission under a Creative Commons Attribution 4.0 International License from ref . Copyright 2023, Springer Nature.…”

“…(E) Enzyme-linked immunosorbent assay (ELISA) for IL-6, IL-1β in the supernatant of reagents stimulated with LPS (1 μg/mL) for 24 h at RAW 264.7. Reprinted (Adapted or Reprinted in part) with permission under a Creative Commons Attribution 4.0 International License from ref . Copyright 2023, Springer Nature.…”

“…(F) Representative images of bacterial colonization in the blood and bacterial counts in peritoneal lavage fluid of mice receiving different treatments. Reprinted (Adapted or Reprinted in part) with permission under a Creative Commons Attribution 4.0 International License from ref . Copyright 2023, Springer Nature.…”