Small, anti-inflammatory nanomotors for the treatment of rheumatoid arthritis

Chemically powered nanomotors help resolve chronic inflammation in rheumatoid arthritis patients.

Just as cars use gas to move, there are microscopic engines that can convert chemical energy into mechanical motion to move inside the body, and they are currently being studied to treat and fight disease.

Scientists from Southern Medical University and Sun Yat-Sen University, both in China, have shown in a recent study the development of a potential nanomotor-based treatment for rheumatoid arthritis, a disease that has not yet been cured.

“Rheumatoid arthritis is a chronic inflammatory disease characterized by joint pain, swelling and damage,” said Yingfeng Tu, principal investigator at the School of Pharmaceutical Sciences at Southern Medical University and lead author of the study. “Although medications, such as steroids, anti-inflammatory drugs and immunosuppressants, can help slow joint destruction and relieve pain, they have side effects and are not completely successful.”

Understanding Rheumatoid Arthritis

In rheumatoid arthritis, immune cells attack healthy cells in the joints and cause inflammation. The main immune cells here are macrophages, which switch from an anti-inflammatory to a pro-inflammatory state, releasing molecules that either alleviate or promote inflammation, respectively.

In inflamed joints, immune cells release signaling molecules called cytokines that cause an overproduction of reactive oxygen species (or ROS), including hydrogen peroxide, which promote the transition of macrophages to their proinflammatory state, leading to a chronic inflammatory state.

In addition, the production of ROS leads to a lack of oxygen in the joints, which causes tissue damage, Tu mentioned.

Tu and his team decided to take advantage of this natural accumulation of hydrogen peroxide in the joints, using it as a chemical fuel to power nanomotors that produce their own oxygen to help resolve chronic inflammation.

“Our results have far-reaching implications not only from a fundamental point of view that uses nanomotors for rheumatoid arthritis, but also from an application point of view, for example as a new strategy to achieve high therapeutic efficiency with minimal side effects for inflammatory diseases,” said Tu.

Construction of an anti-inflammatory nanomotor

Tu and team used manganese dioxide (MnO2) nanoparticles to build their nanobots, as they are known to break down hydrogen peroxide molecules, producing chemical energy in the process that can be used to power their movement. However, because this chemical reaction produces oxidizing molecules that tend to be harmful to biological tissue, the scientists loaded their bots with cerium oxide nanoparticles, which in previous studies have been shown to have powerful antioxidant properties.

The scientists first tested the mobilization of MnO2-motors in saline solution and artificial synovial fluid that mimics joint fluid. As the concentration of hydrogen peroxide in the mixture increased, they observed an increase in the movement of the nanomotor.

Fei Peng, a professor in the School of Materials Science and Engineering at Sun Yat-Sen University and co-author of the study, explained that the presence of hyaluronic acid in the synovial fluid could hinder the movement of their nanomotors. But surprisingly, the team found that at the high concentration of hydrogen peroxide expected in joints with rheumatoid arthritis, MnO2-motors had comparable behavior as in saline. “These results confirmed the efficient propulsion of MnO2– engines [in] synovial fluids,” Peng said.

Furthermore, when adding the nanomotors to cells with pro-inflammatory macrophages, they observed a decrease in the production of pro-inflammatory cytokines and an increase in their anti-inflammatory counterparts, suggesting that their nanomotors have the capacity to mediate the transformation of macrophages from a pro- to an anti-inflammatory state.

But the critical experiment came when testing the nanomotors in vivo, in a rat model of rheumatoid arthritis. The scientists injected the nanomotors into the animals’ joints, and with ultrasound imaging, they monitored oxygen production. “Our MnO2-motor has enhanced diffusion along with continuous oxygen generation, which represents hypoxia [low oxygen] relief and ROS scavenging together to delay disease progression,” said Yingjia Li, professor at Nanfang Hospital of Southern Medical University and co-author of the study.

Li also explained that although MnO2– drivers were injected locally and retained mainly in the knee joints, treated rats showed less swollen paws, reduced bone erosion and lower serum levels of inflammatory cytokines, revealing that the administration of MnO2-bikes can remarkably reduce the overall severity of arthritis.

In view of these promising results, the team is working to introduce MnO2– motorbikes to the clinic. “Although the nanomotors have yet to be tested in humans, we are working on the translational study and foresee its great potential for the therapy of rheumatoid arthritis and other inflammatory diseases,” Tu said.

Reference: Cong Xu, et al., Arthritis Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy, Advanced Science (2022). DOI: 10.1002/advs.202204881

Feature Image Credit: Towfiqu barbhuiya on Unsplash

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