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Published on: November 12, 2020
M2-type exosomes nanoparticles for rheumatoid arthritis therapy via macrophage re-polarization
Abstract:
Imbalance between the activities of pro-inflammatory M1 and anti-inflammatory M2 macrophages in rheumatoid arthritis (RA) induces synovial inflammation and autoimmunity, leading to joint damage. Here we encapsulated a plasmid DNA encoding the anti-inflammatory cytokine interleukin-10 (IL-10 pDNA) and the chemotherapeutic drug betamethasone sodium phosphate (BSP) into biomimetic vector M2 exosomes (M2 Exo) derived from M2-type macrophages. We demonstrate that the loaded exosomes target and reduce inflammation for combined therapy against RA. The in vitro efficiency of the M2 Exo/pDNA/BSP co-delivery system was attributed to the synergistic effect of IL-10 pDNA and BSP, which also promoted M1-to-M2 macrophage polarization by reducing the secretion of pro-inflammatory cytokines (IL-1β, TNF-α) and increasing the expression of IL-10 cytokine. In a mouse model of RA, M2 Exo/pDNA/BSP showed good accumulation at inflamed joint sites, high anti-inflammatory activity, and potent therapeutic effect. The delivery system was non-toxic both in vitro and in vivo. Thus, this system may serve as a promising biocompatible drug carrier and anti-inflammatory agent for RA treatment based on M1-to-M2 macrophage re-polarization.
Insights
This study developed M2 exosomes loaded with IL-10 plasmid DNA and betamethasone sodium phosphate for rheumatoid arthritis (RA) therapy. The novel system effectively reduces inflammation by re-polarizing macrophages, showing promise for RA treatment.
Area of Science:
- Biomedical Engineering
- Immunology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) involves an imbalance between M1 and M2 macrophages, causing synovial inflammation and joint damage.
- Current RA treatments often have limitations and side effects.
- Targeting macrophage polarization presents a potential therapeutic strategy for RA.
Purpose of the Study:
- To develop a novel M2 exosome-based drug delivery system for combined therapy against RA.
- To evaluate the efficacy of co-delivering interleukin-10 plasmid DNA (IL-10 pDNA) and betamethasone sodium phosphate (BSP) using M2 exosomes.
- To investigate the system's ability to re-polarize macrophages from M1 to M2 phenotypes and reduce inflammation.
Main Methods:
- Encapsulation of IL-10 pDNA and BSP into M2 exosomes derived from M2 macrophages.
- In vitro assessment of the M2 Exo/pDNA/BSP system's efficiency and effect on macrophage polarization.
- In vivo evaluation of the system's accumulation, anti-inflammatory activity, and therapeutic effect in a mouse model of RA.
- In vitro and in vivo toxicity assessments.
Main Results:
- The M2 Exo/pDNA/BSP system demonstrated synergistic anti-inflammatory effects in vitro.
- Co-delivery promoted M1-to-M2 macrophage polarization by modulating pro-inflammatory and anti-inflammatory cytokine secretion.
- In a mouse RA model, the system showed targeted accumulation at inflamed joints, significant anti-inflammatory activity, and a potent therapeutic effect.
- The M2 Exo/pDNA/BSP delivery system exhibited no significant toxicity in vitro or in vivo.
Conclusions:
- M2 exosomes are effective biomimetic carriers for co-delivering IL-10 pDNA and BSP for RA treatment.
- The developed system successfully re-polarizes macrophages, reduces inflammation, and alleviates RA symptoms in a preclinical model.
- This biocompatible M2 exosome-based system holds promise as a novel therapeutic agent for rheumatoid arthritis.
