Self-assembled hybrid supraparticles that proteolytically degrade tumor necrosis factor-α

Abstract

The strategies of pathogens to evade the human immune system are highly sophisticated and modulate a variety of inflammatory pathways. The similarities in the demands for modulation of inflammatory responses during disease treatment and during pathogenic infection provide opportunities to use pathogenic virulence factors to develop a new class of therapeutic materials that control inflammation. In this work, we harness a strategy from Porphyromonas gingivalis by transforming its major virulence factor, an arginine-specific cysteine protease, into self-assembled protease-inorganic hybrid supraparticles. The cysteine protease degrades the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α). It is an irreversible inhibition of TNF-α, which avoids some of the adverse effects of current TNF-α antagonists. We fabricated self-assembled porous supraparticles that specifically incorporate the pathogen-derived protease and showed improved inactivation of TNF-α over soluble enzyme, creating a potential therapeutic for various autoimmune diseases or other sources of inflammation.