Department of Chemical Engineering and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology , Monash University , Clayton , Victoria 3800 , Australia.
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute , Monash University , Clayton , Victoria 3800 , Australia.
ACS Appl Mater Interfaces. 2019 Sep 25;11(38):34676-34687. doi: 10.1021/acsami.9b10853. Epub 2019 Sep 13.
Nanoparticle-cell interactions between silica nanomaterials and mammalian cells have been investigated extensively in the context of drug delivery, diagnostics, and imaging. While there are also opportunities for applications in infectious disease, the interactions of silica nanoparticles with pathogenic microbes are relatively underexplored. To bridge this knowledge gap, here, we investigate the effects of organosilica nanoparticles of different sizes, concentrations, and surface coatings on surface association and viability of the major human fungal pathogen . We show that uncoated and PEGylated organosilica nanoparticles associate with in a size and concentration-dependent manner, but on their own, do not elicit antifungal activity. The particles are also shown to associate with human white blood cells, in a similar trend as observed with , and remain noncytotoxic toward neutrophils. Smaller particles are shown to have low association with in comparison to other sized particles and their association with blood cells was also observed to be minimal. We further demonstrate that by chemically immobilizing the clinically important echinocandin class antifungal drug, caspofungin, to PEGylated nanoparticles, the cell-material interaction changes from benign to antifungal, inhibiting growth when provided in high local concentration on a surface. Our study provides the foundation for defining how organosilica particles could be tailored for clinical applications against . Possible future developments include designing biomaterials that could detect, prevent, or treat bloodstream infections, which at present have very high patient mortality.
纳米颗粒与哺乳动物细胞之间的相互作用已经在药物输送、诊断和成像等领域得到了广泛的研究。虽然在传染病领域也有应用的机会，但硅纳米材料与致病微生物的相互作用相对较少被探索。为了弥补这一知识空白，在这里，我们研究了不同大小、浓度和表面涂层的有机硅纳米颗粒对主要人类真菌病原体 的表面结合和活力的影响。我们表明，未涂层和 PEG 化的有机硅纳米颗粒以大小和浓度依赖的方式与 结合，但单独使用时，不会引起抗真菌活性。还表明这些颗粒与人白细胞结合的趋势与观察到的 相似，并且对中性粒细胞没有细胞毒性。与其他大小的颗粒相比，较小的颗粒与 的结合率较低，与血细胞的结合也很少。我们进一步证明，通过将临床上重要的棘白菌素类抗真菌药物卡泊芬净化学固定在 PEG 化纳米颗粒上，细胞-材料相互作用从良性变为抗真菌，当在表面上以高局部浓度提供时，抑制 的生长。我们的研究为定义如何针对 定制有机硅颗粒以用于临床应用提供了基础。未来可能的发展包括设计能够检测、预防或治疗血流感染的生物材料，目前这些感染的患者死亡率非常高。
