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

在之前的项目中，我们在银和不同贵金属的基础上合成了双金属纳米颗粒（约10纳米）。我们对它们的微观结构和生物活性进行了比较研究。在这个提议中，我们想把重点放在以银和铂（AgPt）为基础的超小双金属纳米颗粒（约2纳米）上。这些应以单金属和合金形式制备。这种超小的纳米颗粒在细胞中特别容易移动，其大小与蛋白质等生物大分子相当。它们的生物学途径和作用只是很少被研究和理解。我们想要解决以下问题：哪一种合成途径可以得到尺寸和内部结构均质的超小AgPt纳米颗粒样品？超小AgPt纳米颗粒通过何种机制（如内吞作用或被动运输）进入细胞？它们是如何在细胞内运输的又在哪里定位？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有趣。哪些细胞生物学效应是由双金属纳米颗粒引起的？我们想把重点放在机理分析和细胞活化，直到细胞死亡。超小AgPt纳米颗粒有哪些抗菌作用？我们想把重点放在细胞膜的流动性和抗生物膜的活性。在这种情况下，我们还想分析纳米颗粒被细菌吸收的程度。我们如何将生物效应与银离子的释放和组织细胞和细菌的摄取联系起来？由于抗菌银的存在，AgPt系统具有临床意义。一个中心假设是合金银铂纳米颗粒具有增强的抗菌作用。

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.