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

Abstract

The expression of hypoxia-inducible factor-1α (HIF-1α) 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-1α, 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.

Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing

“…Among them, CH7 made the highest oxygen level, up to 11.0 mg/L. The peak concentration and the peak time of oxygen were not good as that with the illumination commonly used (short light time with high density) 22 , 36 , 37 , but the oxygen level could be maintained longer. As the tissue remodeled, fluid exchange through the wound gap was inhibited, while oxygen permeating through the re-generated skin gradually played an important role ( Supporting Information Fig.…”

Microbial‐Enabled Photosynthetic Oxygenation for Disease Treatment

“…So, cyanobacteria are also used to improve joint hypoxia and improve the treatment of RA. NIR‐controlled cyanobacteria micro‐nanodevice [ 212 ] was reported to produce oxygen at the joint to enhance the therapeutic effect of the antirheumatic drug methotrexate (MTX) and reduce HIF‐1α expression which could enhance the polarization of M2‐type macrophages and reduce inflammation of RA. The cyanobacteria micro‐nanodevice in temperature‐sensitive hydrogel, PLCA‐PEG‐PLCA, (CMP) system consisted of NIR‐controlled cyanobacteria micro‐nanodevice, MTX, and temperature‐sensitive hydrogels, in which the micro‐nanodevice was formed by Cyanobacteria PCC 7942 internalized UCNPs (lanthanide NaYF4: Tm, Yb, Nd), which could be converted into blue light by NIR laser to induce cyanobacteria to produce oxygen in situ through photosynthesis.…”

Manganese‐Based Immunomodulatory Nanocomposite with Catalase‐Like Activity and Microwave‐Enhanced ROS Elimination Ability for Efficient Rheumatoid Arthritis Therapy

“…[6][7][8] M1 phenotype macrophages www.advancedsciencenews.com www.small-journal.com secrete several pro-inflammatory cytokines, such as tumor necrosis factor-𝛼 (TNF-𝛼), interleukin-1𝛽 (IL-1𝛽), and interleukin-6 (IL-6), increasing the content of inducible nitric oxide synthase (iNOS) and leading to a series of the oxidative-stressstimulated and inflammatory reactions. [9] Conversely, M2 phenotype macrophages secrete various anti-inflammatory cytokines, such as interleukin-10 (IL-10), interleukin-4 (IL-4), and arginase-1 (Arg-1), enhancing the specific expression of mannose receptor CD206 and promoting the resolution of inflammation. [10] Thus, re-polarizing M1 macrophages into M2 phenotype may be an effective way to treat RA.…”