Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08028, Spain.
Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
ACS Nano. 2022 May 24;16(5):7547-7558. doi: 10.1021/acsnano.1c11013. Epub 2022 Apr 29.
The increasing resistance of bacteria to existing antibiotics constitutes a major public health threat globally. Most current antibiotic treatments are hindered by poor delivery to the infection site, leading to undesired off-target effects and drug resistance development and spread. Here, we describe micro- and nanomotors that effectively and autonomously deliver antibiotic payloads to the target area. The active motion and antimicrobial activity of the silica-based robots are driven by catalysis of the enzyme urease and antimicrobial peptides, respectively. These antimicrobial motors show micromolar bactericidal activity against different Gram-positive and Gram-negative pathogenic bacterial strains and act by rapidly depolarizing their membrane. Finally, they demonstrated autonomous anti-infective efficacy in a clinically relevant abscess infection mouse model. In summary, our motors combine navigation, catalytic conversion, and bactericidal capacity to deliver antimicrobial payloads to specific infection sites. This technology represents a much-needed tool to direct therapeutics to their target to help combat drug-resistant infections.
细菌对现有抗生素的耐药性不断增强，这在全球范围内对公共健康构成了重大威胁。目前大多数抗生素治疗方法都受到向感染部位输送效果不佳的限制，导致非靶向的副作用以及耐药性的产生和传播。在这里，我们描述了能够有效且自主地将抗生素有效载荷输送到目标区域的微纳米马达。基于二氧化硅的机器人的主动运动和抗菌活性分别由酶脲酶和抗菌肽的催化作用驱动。这些抗菌马达对不同的革兰氏阳性和革兰氏阴性致病菌株表现出微摩尔级的杀菌活性，并通过快速去极化其细胞膜起作用。最后，它们在具有临床相关性的脓肿感染小鼠模型中展示了自主抗感染功效。总之，我们的马达将导航、催化转化和杀菌能力结合起来，将抗菌有效载荷递送到特定的感染部位。这项技术代表了一种急需的工具，可以将治疗药物靶向到目标部位，有助于对抗耐药性感染。
