NIR-Responsive Spatiotemporally Controlled Cyanobacteria Micro-Nanodevice for Intensity-Modulated Chemotherapeutics in Rheumatoid Arthritis

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.