Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, 70569 Stuttgart, Germany.; Institute for Physical Chemistry, University of Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
Institute for Medical Engineering and Department of Mechanical Engineering, Technische Universität München, Boltzmannstrasse 11, 85748 Garching, Germany.
Sci Adv. 2015 Dec 11;1(11):e1500501. doi: 10.1126/sciadv.1500501. eCollection 2015 Dec.
In the body, mucus provides an important defense mechanism by limiting the penetration of pathogens. It is therefore also a major obstacle for the efficient delivery of particle-based drug carriers. The acidic stomach lining in particular is difficult to overcome because mucin glycoproteins form viscoelastic gels under acidic conditions. The bacterium Helicobacter pylori has developed a strategy to overcome the mucus barrier by producing the enzyme urease, which locally raises the pH and consequently liquefies the mucus. This allows the bacteria to swim through mucus and to reach the epithelial surface. We present an artificial system of reactive magnetic micropropellers that mimic this strategy to move through gastric mucin gels by making use of surface-immobilized urease. The results demonstrate the validity of this biomimetic approach to penetrate biological gels, and show that externally propelled microstructures can actively and reversibly manipulate the physical state of their surroundings, suggesting that such particles could potentially penetrate native mucus.
在体内,黏液通过限制病原体的渗透提供了重要的防御机制。因此,它也是高效递送基于颗粒的药物载体的主要障碍。特别是酸性胃衬里难以克服,因为黏蛋白糖蛋白在酸性条件下形成粘弹性凝胶。幽门螺杆菌细菌已经开发出一种通过产生酶脲酶来克服黏液屏障的策略,脲酶局部提高 pH 值,从而使黏液液化。这使得细菌能够在黏液中游泳并到达上皮表面。我们提出了一种反应性磁性微推进器的人工系统,该系统通过利用表面固定化的脲酶来模拟这种通过胃黏蛋白凝胶的策略。结果证明了这种仿生方法穿透生物凝胶的有效性,并表明外部推进的微结构可以主动和可逆地操纵其周围环境的物理状态,这表明这些颗粒有可能穿透天然黏液。