Abstract

Whereas nanotoxicity is intensely studied in mammalian systems, our knowledge of desired or unwanted nano-based effects for microbes is still limited. Fungal infections are global socio-economic health and agricultural problems, and current chemical antifungals may induce adverse side-effects in humans and ecosystems. Thus, nanoparticles are discussed as potential novel and sustainable antifungals via the desired nanotoxicity but often fail in practical applications. In our study, we found that nanoparticles’ toxicity strongly depends on their binding to fungal spores, including the clinically relevant pathogen Aspergillus fumigatus as well as common plant pests, such as Botrytis cinerea or Penicillum expansum. Employing a selection of the model and antimicrobial nanoparticles, we found that nanoparticle-spore complex formation is influenced by the NM’s physicochemical properties, such as size, identified as a key determinant for our silica model particles. Biomolecule coronas acquired in pathophysiologically and ecologically relevant environments, protected fungi against nanoparticle-induced toxicity as shown by employing antimicrobial ZnO, Ag, or CuO nanoparticles as well as dissolution-resistant quantum dots. Mechanistically, dose-dependent corona-mediated resistance was conferred via reducing the physical adsorption of nanoparticles to fungi. The inhibitory effect of biomolecules on nano-based toxicity of Ag NPs was further verified in vivo, using the invertebrate Galleria mellonella as an alternative non-mammalian infection model. We provide the first evidence that biomolecule coronas are not only relevant in mammalian systems but also for nanomaterial designs as future antifungals for human health, biotechnology, and agriculture.

摘要

尽管在哺乳动物系统中对纳米毒性进行了深入研究，但是我们对微生物所需或不希望的基于纳米的作用的知识仍然有限。真菌感染是全球社会经济健康和农业问题，当前的化学抗真菌剂可能在人类和生态系统中引起不利的副作用。因此，通过期望的纳米毒性，纳米颗粒被认为是潜在的新颖和可持续的抗真菌剂，但是在实际应用中常常失败。在我们的研究中，我们发现纳米颗粒的毒性在很大程度上取决于它们与真菌孢子的结合，包括临床相关的病原体烟曲霉和灰霉病菌或普通青霉菌等常见植物害虫。。通过选择模型和抗菌纳米颗粒，我们发现纳米颗粒-孢子复合物的形成受NM物理化学性质（例如大小）的影响，而NM的物理化学性质被确定为二氧化硅模型颗粒的关键决定因素。在病理生理和生态相关环境中获得的生物分子电晕通过使用抗菌性ZnO，Ag或CuO纳米颗粒以及耐溶解的量子点显示，可以保护真菌免受纳米颗粒诱导的毒性。从机理上讲，剂量依赖性电晕介导的抗性是通过减少纳米颗粒对真菌的物理吸附来实现的。使用无脊椎动物白花蛇毒（Galleria mellonella），在体内进一步验证了生物分子对银纳米颗粒纳米级毒性的抑制作用。作为替代的非哺乳动物感染模型。我们提供的第一个证据是，生物分子电晕不仅与哺乳动物系统有关，而且与纳米材料设计有关，作为人类健康，生物技术和农业的未来抗真菌剂。