Microgels as Platforms for Antibody-Mediated Cytokine Scavenging

Therapeutic antibodies are the key treatment option for various cytokine-mediated diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, systemic injection of these antibodies can cause side effects and suppress the immune system. Moreover, clearance of therapeutic antibodies from the blood is limiting their efficacy. Here, water-swollen microgels are produced with a size of 25 mu m using droplet-based microfluidics. The microgels are functionalized with TNF alpha antibodies to locally scavenge the pro-inflammatory cytokine TNF alpha. Homogeneous distribution of TNF alpha-antibodies is shown throughout the microgel network and demonstrates specific antibody-antigen binding using confocal microscopy and FLIM-FRET measurements. Due to the large internal accessibility of the microgel network, its capacity to bind TNF alpha is extremely high. At a TNF alpha concentration of 2.5 mu g mL(-1), the microgels are able to scavenge 88% of the cytokine. Cell culture experiments reveal the therapeutic potential of these microgels by protecting HT29 colorectal adenocarcinoma cells from TNF alpha toxicity and resulting in a significant reduction of COX II and IL8 production of the cells. When the microgels are incubated with stimulated human macrophages, to mimic the in vivo situation of inflammatory bowel disease, the microgels scavenge almost all TNF alpha that is produced by the cells.

Automated summary

Water-swollen microgels functionalized with TNF alpha antibodies can scavenge and protect cells from the pro-inflammatory cytokine TNF alpha, showing potential therapeutic effects for cytokine-mediated diseases.