Department of Biomedical Engineering, Vanderbilt University , VU Station B 351631, Nashville, Tennessee 37235-1631, United States.
Vanderbilt University Medical Center, Department of Medicine, Division of Infectious Disease, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
ACS Appl Mater Interfaces. 2017 Aug 16;9(32):26719-26730. doi: 10.1021/acsami.7b07304. Epub 2017 Aug 4.
Acinetobacter baumannii is a Gram-negative bacterium of increasing concern due to its virulence and persistence in combat and healthcare environments. The incidence of both community-acquired and nosocomial A. baumannii infections is on the rise in foreign and domestic healthcare facilities. Treatment options are limited due to the acquisition of multidrug resistance to the few effective antibiotics. Currently, the most effective pharmaceutically based treatment for multidrug-resistant A. baumannii infections is the antibiotic colistin (polymyxin E). To minimize side effects associated with administration of colistin or other toxic antimicrobial agents, we propose the development of a nanotechnology-mediated treatment strategy. In this design-based effort, colistin-functionalized multilayered, inorganic, magnetoplasmonic nanoconstructs were fabricated to bind to the surface of A. baumannii. This result, for the first time, demonstrates a robust, pharmaceutical-based motif for high affinity, composite nanoparticulates targeting the A. baumannii surface. The antibiotic-activated nanomaterials demonstrated cytocompatibility with human cells and no acute bacterial toxicity at nanoparticle to bacterial concentrations <10 000:1. The magnetomotive characteristics of the nanomaterial enabled magnetic extraction of the bacteria. In a macroscale environment, maximal separation efficiencies exceeding 38% were achieved. This result demonstrates the potential for implementation of this technology into micro- or mesofluidic-based separation environments to enhance extraction efficiencies. The future development of such a mesofluidic-based, nanotechnology-mediated platform is potentially suitable for adjuvant therapies to assist in the treatment of sepsis.
鲍曼不动杆菌是一种革兰氏阴性细菌，由于其在战斗和医疗环境中的毒力和持久性而引起越来越多的关注。在国外和国内的医疗机构中，社区获得性和医院获得性鲍曼不动杆菌感染的发病率都在上升。由于对少数有效抗生素产生了多药耐药性，治疗选择有限。目前，治疗多药耐药鲍曼不动杆菌感染最有效的药物治疗是抗生素黏菌素（多粘菌素 E）。为了最大限度地减少与黏菌素或其他有毒抗菌药物给药相关的副作用，我们提出了开发纳米技术介导的治疗策略。在这项基于设计的努力中，制备了黏菌素功能化的多层无机磁等离子体纳米结构，以与鲍曼不动杆菌的表面结合。这一结果首次证明了一种强大的、基于药物的 motif，用于高亲和力的、针对鲍曼不动杆菌表面的复合纳米颗粒。抗生素激活的纳米材料与人类细胞具有细胞相容性，并且在纳米颗粒与细菌浓度<10000:1 时没有急性细菌毒性。纳米材料的磁动特性使细菌能够进行磁性提取。在宏观环境中，实现了超过 38%的最大分离效率。这一结果表明，该技术有可能被引入微或中尺度的分离环境中，以提高提取效率。这种基于中尺度的纳米技术介导的平台的未来发展，对于辅助治疗败血症是潜在合适的。
