Synthesis, structure, and biological effects of ultrasmall (1-2 nm) bimetallic silver-platinum nanoparticles

在前面的项目中，我们以银和不同的贵金属为基础合成了双金属纳米颗粒(约10 nm)。我们对它们的微观结构和生物活性进行了比较研究。在这项提议中，我们希望在银和铂(AgPT)的基础上，重点研究超小的双金属纳米颗粒(约2 nm)。这种超小的纳米粒子在细胞中尤其具有流动性，其大小可与蛋白质等生物大分子相媲美。它们的生物学途径和影响只被很少地调查和了解。我们想要解决以下问题：在尺寸和内部结构方面，哪些合成路线会导致超小AgPT纳米颗粒的均匀样品？超小AgPT纳米颗粒进入细胞的机制是什么(例如，吞噬或被动转运)？它们是如何在细胞内运输的，它们被定位在哪里？在这里，由于银的存在(遗传毒性)，它们穿透细胞核的能力特别令人感兴趣。双金属纳米颗粒引起了哪些细胞生物学效应？我们想要关注的是机制分析和细胞激活，直到细胞死亡。超小的AgPT纳米粒子会产生哪些抗菌作用？我们想把重点放在细胞膜的流动性和抗生物膜的活性上。在这种情况下，我们还想分析纳米粒子被细菌摄取的程度。我们如何将生物效应与银离子的释放以及组织细胞和细菌的摄取联系起来？由于抗菌银的存在，系统的AgPT具有临床意义。一个中心假设是，合金化的银-铂纳米颗粒具有增强的抗菌效果。

In the preceding project we synthesized bimetallic nanoparticles (around 10 nm) on the basis of silver and different noble metals. We have carried out comparative investigations on their microstructure and their biological activity. In this proposal, we want to focus on ultrasmall bimetallic nanoparticles (about 2 nm) on the basis of silver and platinum (AgPt). These shall be prepared both in monometallic and alloyed form.Such ultrasmall nanoparticles are especially mobile in cells and have a size which is comparable to biological macromolecules like proteins. Their biological pathways and effects are only poorly investigated and understood. We want to address the following questions:Which synthetic routes lead to homogeneous samples of ultrasmall AgPt nanoparticles with respect to size and internal domain structure?By which mechanisms (e.g. endocytosis or passive transport) are ultrasmall AgPt nanoparticles entering cells? How are they transported inside the cells and where are they localized? Here, their ability to penetrate the cell nucleus is especially interesting due to the presence of silver (genotoxicity).Which cell-biological effects are caused by the bimetallic nanoparticles? We want to focus on the mechanistic analysis and the cell activation, up to cell death.Which antimicrobial effects are caused by ultrasmall AgPt nanoparticles? We want to focus on the cell membrane fluidity and the activity against biofilms. In this context we also want to analyse to which degree the nanoparticles are taken up by bacteria.How can we correlate the biological effects with the release of silver ions and the uptake by tissue cells and bacteria?Due the presence of antibacterial silver, the system AgPt has clinical relevance. A central hypothesis is the assumption that alloyed silver-platinum nanoparticles have an enhanced antimicrobial effect.