Biohybrid microrobots regulate colonic cytokine and epithelium barrier in inflammatory bowel disease

Cytokines have been identified as key contributors to the development of inflammatory bowel disease (IBD), yet conventional treatments often prove inadequate and carry substantial side effects. Here, we show an innovative biohybrid robotic system, termed ‘algae-MΦNP-robot’, for addressing IBD by actively neutralizing colonic cytokine levels. Our approach combines moving green microalgae with macrophage membrane-coated nanoparticles (MΦNPs) to efficiently capture pro-inflammatory cytokines ‘on-the-fly’. The dynamic algae-MΦNP-robots outperform static counterparts by enhancing cytokine removal through continuous movement, better distribution, and extended retention in the colon. This system is encapsulated within an oral capsule, which shields it from gastric acidity and ensures functionality upon reaching the targeted disease site. The resulting algae-MΦNP-robot capsule effectively regulates cytokine levels, facilitating the healing of damaged epithelial barriers. It shows markedly improved prevention and treatment efficacy in a mouse model of IBD and demonstrates an excellent biosafety profile. Overall, our biohybrid algae-MΦNP-robot system offers a promising and efficient solution for IBD, addressing cytokine-related inflammation effectively.

Methods
The dataset was the collection of the data which were used for Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, and Figure 6. The detailed information of each data collection was included in the 'Materials and Methods' section of the main manuscript.