Atomically precise, multi-ligand functionalised metal nanoclusters to combat bacterial antibiotic resistance

原子精确的多配体功能化金属纳米簇可对抗细菌抗生素耐药性

• 批准号: 2882405
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2882405
• 关键词: Atomically; precise; multi; ligand; functionalised

Bacterial antibiotic resistance (BAR) is "one of the biggest threats to global health". While traditional antibiotic discovery is valuable, it is lengthy, expensive, and moreover, rapid BAR is inevitable once in clinical use, due to evolutionary adaptation of bacteria to antibiotic actions. Whereas nanomaterials can offer several antibacterial modes in one agent, making it much harder for bacteria to develop resistance. Some nanomaterials can re-vitalise antibiotics against multidrug resistant bacteria, thus can offer a cheaper, faster and robust alternative to antibiotics to address BAR challenge. Despite great advance, most researches are focused on improving nanomaterials' in vitro antibacterial potencies with little consideration of translation. To date, most antibacterial nanomaterials remain mixed size particles without defined chemical formula, and exhibit limited in vivo stability, biocompatibility and undesirable body clearance. These have greatly limited their potential for clinical translation. We will address such issues by developing atomically precise, multi-ligand functionalised M25 nanoclusters (NCs). We target the M25SR18 NC (SR = thiol ligand) owing to high stability, well-defined molecular structure, and facile synthesis method. We will engineer NCs with excellent stability, biocompatibility and antibacterial potency via multi-functional ligand coating (each for antibacterial potency, in vivo stability & targeting). We will directly track NC-cell interactions, intracellular trafficking and bio-distribution via NC's strong NIR fluorescence. We will evaluate NCs' antibacterial properties using bacteria culture and biofilm models with & without antibiotics to probe potential synergy and establish surface-structure-function relationships and a design rule for antibiotic NCs.

细菌抗生素耐药性（BAR）是“对全球健康的最大威胁之一”。虽然传统的抗生素发现是有价值的，但由于细菌对抗生素作用的进化适应，它是漫长，昂贵且此外，不可避免的临床用途是不可避免的。而纳米材料可以在一种药物中提供几种抗菌模式，从而使细菌产生抗性更加困难。一些纳米材料可以使对耐多药细菌的抗生素重新提高，因此可以为抗生素提供更便宜，更快，稳健的替代品来应对bar挑战。尽管有很大的进步，但大多数研究都集中在改善纳米材料的体外抗菌效力上，而几乎不考虑翻译。迄今为止，大多数抗菌纳米材料仍然是混合尺寸的颗粒，而没有定义的化学式，并且体内稳定性，生物相容性和不良身体间隙的效果有限。这些极大地限制了它们的临床翻译潜力。我们将通过开发原子上精确的多配体功能化的M25纳米群（NCS）来解决此类问题。由于高稳定性，定义明确的分子结构和简化的合成方法，我们针对M25SR18 NC（SR =硫醇配体）。我们将通过多功能配体涂层（每种抗菌效力，体内稳定性和靶向）设计具有出色稳定性，生物相容性和抗菌效力的NC。我们将直接通过NC的强NIR荧光跟踪NC细胞相互作用，细胞内运输和生物分布。我们将使用具有抗生素的细菌培养物和生物膜模型来评估NCS的抗菌特性，以探测潜在的协同作用，并建立表面结构功能关系和抗生素NCS的设计规则。