Giri Karuna, Yepes Laura Rivas, Duncan Bradley, Parameswaran Praveen Kolumam, Yan Bo, Jiang Ying, Bilska Marcela, Moyano Daniel F, Thompson Mike, Rotello Vincent M, Prakash Y S
Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 1 St SW, Rochester, MN 55905.
Department of Anesthesiology, Mayo Clinic, 200 1 St SW, Rochester, MN 55905; Department of Physiology & Biomedical Engineering, Mayo Clinic, 200 1 St SW, Rochester, MN 55905.
RSC Adv. 2015;5(128):105551-105559. doi: 10.1039/C5RA16305F. Epub 2015 Dec 1.
Bacterial biofilms are associated with persistent infections that are resistant to conventional antibiotics and substantially complicate patient care. Surface engineered nanoparticles represent a novel, unconventional approach for disruption of biofilms and targeting of bacterial pathogens. Herein, we describe the role of surface charge of gold nanoparticles (AuNPs) on biofilm disruption and bactericidal activity towards and which are important ventilator associated pneumonia (VAP) pathogens. In addition, we study the toxicity of charged AuNPs on human bronchial epithelial cells. While 100% positively charged AuNP surface was uniformly toxic to both bacteria and epithelial cells, reducing the extent of positive charge on the AuNP surface at moderate concentrations prevented epithelial cell toxicity. Reducing surface charge was however also less effective in killing bacteria. Conversely, increasing AuNP concentration while maintaining a low level of positivity continued to be bactericidal and disrupt the bacterial biofilm and was less cytotoxic to epithelial cells. These initial studies suggest that modulation of AuNP surface charge could be used to balance effects on bacteria vs. airway cells in the context of VAP, but the therapeutic window in terms of concentration vs. surface positive charge may be limited. Additional factors such as hydrophobicity may need to be considered in order to design AuNPs with specific, beneficial effects on bacterial pathogens and their biofilms.
细菌生物膜与对传统抗生素具有抗性的持续性感染相关,这极大地增加了患者护理的复杂性。表面工程化纳米颗粒代表了一种破坏生物膜和靶向细菌病原体的新型非传统方法。在此,我们描述了金纳米颗粒(AuNP)的表面电荷对生物膜破坏以及对肺炎克雷伯菌和鲍曼不动杆菌(它们是重要的呼吸机相关性肺炎(VAP)病原体)的杀菌活性的作用。此外,我们研究了带电AuNP对人支气管上皮细胞的毒性。虽然100%带正电的AuNP表面对细菌和上皮细胞均具有一致的毒性,但在中等浓度下降低AuNP表面的正电荷程度可防止上皮细胞毒性。然而,降低表面电荷对杀灭细菌的效果也较差。相反,在保持低正电荷水平的同时增加AuNP浓度仍具有杀菌作用并能破坏细菌生物膜,且对上皮细胞的细胞毒性较小。这些初步研究表明,在VAP的背景下,调节AuNP表面电荷可用于平衡对细菌与气道细胞的影响,但在浓度与表面正电荷方面的治疗窗口可能有限。为了设计出对细菌病原体及其生物膜具有特定有益作用的AuNP,可能需要考虑诸如疏水性等其他因素。