期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 16, 页码 18423-18431出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c20514
关键词
rheumatoid arthritis (RA); cyanobacteria micro-nanodevice; HIF-1 alpha; oxygen; macrophages; chemotherapy
资金
- National Natural Science Foundation of China [32000999, 81925020, 81630051]
- Key Project of Tianjin Natural Science Foundation [19JCZDJC34100]
- Open Project of State Key Laboratory of Oral Diseases [SKLOD2021OF07]
This study introduces a cyanobacteria micro-nanodevice that can produce oxygen in RA joints, reducing HIF-1 alpha expression, decreasing M1 macrophage numbers, and inducing polarization of M2 macrophages for effective RA treatment.
The expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) is upregulated in hypoxic environments at the lesions of rheumatoid arthritis (RA), which promoted the polarization of proinflammatory M1 macrophages and inhibited the differentiation of anti-inflammatory M2 to deteriorate synovial inflammation. Since oxygen scarcity at the joints causes an imbalance of macrophages M1 and M2, herein, we designed a cyanobacteria micro-nanodevice that can be spatiotemporally controlled in vivo to continuously producing oxygen in the RA joints for the downregulation of the expression of HIF-1 alpha, thereby reducing the amounts of M1 macrophages and inducing the polarization of M2 macrophages for chemically sensitized RA treatment. The forthputting of temperature-sensitive hydrogel guaranteed the safety of cyanobacteria micro-nanodevice in vivo. Furthermore, the oxygen produced by cyanobacteria micro-nanodevice in a sustained manner enhanced the therapeutic effect of the antirheumatic drug methotrexate (MTX) and discouraged inflammation and bone erosion at RA. This study provided a new approach for the RA treatment of spatiotemporal-controlled release of oxygen in vitro.
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