期刊
JOURNAL OF CONTROLLED RELEASE
卷 341, 期 -, 页码 16-30出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.11.019
关键词
Rheumatoid arthritis; Exosomes; Macrophage polarization; Synergistic effect; Anti-inflammatory activity
资金
- National Natural Science Foundation of China [81803478]
- Science and Technology Project of Luzhou Government [2019-JYJ-51]
- Science and Technology Project of the Health Planning Committee of Sichuan [18ZD036]
The combination therapy using M2 macrophage exosomes loaded with IL-10 pDNA and BSP was effective in targeting and reducing inflammation in RA. The synergistic effects of IL-10 pDNA and BSP promoted M1-to-M2 macrophage polarization, demonstrating high anti-inflammatory activity and therapeutic effect against RA.
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-1 beta, TNF-alpha) 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.
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