Localised antibiotic delivery and release with luminescent mesoporous silica nanoparticles

抗菌素耐药性是全球公共卫生和经济发展面临的最具挑战性的威胁之一，据估计，到2050年，抗菌素耐药性每年将额外造成1000万人死亡，并给全球经济造成高达100万亿美元的损失。除了有限的药物之外，由于AMR（内在或获得性）机制，目前更多的抗生素化合物正变得不那么有效。革兰氏阴性菌；铜绿假单胞菌或大肠杆菌)是最难治疗的一类病原体之一，因为它们的膜结构使它们相对不被许多抗生素渗透。因此，为了增加这些细胞对抗生素的摄取，在这个项目中，我们将开发纳米颗粒来提高抗生素局部递送的效率。二氧化硅基纳米多孔材料具有高孔隙体积（> 0.9 cm3/g）和大表面积（> 900 m2/g）的优点。我们将使用不同的功能化途径来检查抗生素释放的效率，表面的效果和靶向载体来检查细菌细胞的摄取。我们将使用发光金属配合物将发光信号引入纳米颗粒，以监测抗菌剂的细胞摄取和释放。

Antibacterial resistance (AMR) of one of the most challenging threats to global public health and economic development estimated to cause an additional 10 million deaths per year and a loss of up to US$100 trillion from the global economy by 2050. Besides the limited drugs in the pipeline, more current antibiotic compounds are becoming less effective due to AMR (intrinsic or acquired) mechanisms. Gram-negative bacteria (eg. P. aeruginosa or E. coli) are one of the most difficult class of pathogens to treat because their membrane structure makes them relatively impermeable to many antibiotics. Thus, in order to increase the antibiotic uptake in such cells, in this project we will develop nanoparticles to increase the efficiency of antibiotic delivery localisation. Silica based nanoporous materials are good candidates with high pore volume > 0.9 cm3/g and large surface area (> 900 m2/g). We will be using different functionalisation routes to examine the efficiency of antibiotic release, effect of the surface and the targeting vectors to examine uptake by bacterial cells. We will use luminescent metal complexes to introduce luminescent signal to nanoparticles to monitor cell uptake and tracking of antibacterial agent release.