Park Won Min, Yee Christine M, Champion Julie A
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Drive NW, Atlanta, GA 30332, USA.
J Mater Chem B. 2016 Mar 7;4(9):1633-1639. doi: 10.1039/c5tb01647a. Epub 2015 Nov 2.
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.
病原体逃避人类免疫系统的策略非常复杂，且能调节多种炎症途径。疾病治疗过程中与病原体感染过程中对炎症反应调节的需求存在相似性，这为利用病原体毒力因子开发一类新型的控制炎症的治疗材料提供了机会。在这项工作中，我们采用了牙龈卟啉单胞菌的一种策略，即将其主要毒力因子——一种精氨酸特异性半胱氨酸蛋白酶，转化为自组装蛋白酶 - 无机杂化超粒子。这种半胱氨酸蛋白酶可降解促炎细胞因子肿瘤坏死因子 -α（TNF-α）。这是对TNF-α的不可逆抑制，避免了当前TNF-α拮抗剂的一些不良反应。我们制备了特异性掺入病原体衍生蛋白酶的自组装多孔超粒子，与可溶性酶相比，其对TNF-α的失活作用有所改善，为各种自身免疫性疾病或其他炎症来源创造了一种潜在的治疗方法。
