Yingfeng Tu/Yingjia Li, Southern Medical University, Fei Peng, Sun Yat-sen University: Joint microenvironment-driven nanorobots for precise active treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes joint swelling and pain, leading to persistent synovitis and irreversible joint disability, posing a serious threat to human health
.
In the microenvironment of RA, increased oxygen demand and excessive ROS production can induce macrophage polarization into pro-inflammatory M1 macrophages, which play a key role
in exacerbating inflammation.
Therefore, eliminating ROS in the inflammatory joint microenvironment and improving hypoxic status is a potential RA treatment that can drive the transition
of pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype.
Recently, Professor Tu Yingfeng, Professor Li Yingjia and Professor Peng Fei of Sun Yat-sen University have developed a joint microenvironment-driven nanorobot (_MnO2-motor) using nanorobots to actively deliver and enhance the ability of diffusion, and use it for precision treatment
of RA.
(Figure 1)

Figure 1.
Schematic diagram of the in vivo therapeutic mechanism of MnO_2-motor on hypoxic inflammatory joints by synergistic oxygen production and ROS clearance
.
Nanomotors driven by the arthritis microenvironment improve hypoxic state while clearing ROS and regulating macrophage phenotype
.

Specifically, MnO2-motors achieve catalytic regulation
of the RA microenvironment by consuming excess_H2O2and synergistic production of oxygen.
Oxygen generated in the_H2O2-richarthritis microenvironment can not only enable ultrasound imaging as an inflammation detector, but also improve the hypoxic synovial microenvironment as a propellant
to promote diffusion.
By producing oxygen and clearing inflammation,_MnO2-motor inhibits the repolarization of pro-inflammatory macrophages, thereby significantly reducing the secretion
of multiple pro-inflammatory cytokines in vitro and in vivo.
The therapeutic effect of MnO 2-motor was also confirmed in the CIA rat model (Figure 2), and it was confirmed by imaging, histology and serological examination that MnO_2-motor treatment can effectively relieve synovial infiltration and cartilage damage, and slow down disease progression
.
In summary, this study fully confirms that joint microenvironment-driven nanorobots have important application value
in the treatment of rheumatoid arthritis and antioxidant therapy.

Figure 2.
Imaging analysis and evaluation of pathological features in MnO_2-motor therapy in a rat model of CIA

The work was titled "Arthritic Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy.
" Published in Advanced Science (DOI: 10.
1002/advs.
202204881), the first authors of the article are Xu Jun, a 20-level doctoral student and Jiang Yuejun, a 20-level master's student of Southern Medical University, the corresponding author is Professor Tu Yingfeng of Southern Medical University, and the co-corresponding authors are Professor Li Yingjia of Southern Hospital of Southern Medical University and Professor
Peng Fei of Sun Yat-sen University.