The development of effective therapies to control methicillin-resistant Staphylococcus aureus (MRSA) infections is challenging because antibiotics can be degraded by the production of certain enzymes, for example, β-lactamases. Additionally, the antibiotics themselves fail to penetrate the full depth of biofilms formed from extracellular polymers. Nanoparticle-based carriers can deliver antibiotics with better biofilm penetration, thus combating bacterial resistance. In this study, we describe a general approach for the construction of β-lactam antibiotics and β-lactamase inhibitors co-delivery of nanoantibiotics based on metal–carbenicillin framework-coated mesoporous silica nanoparticles (MSN) to overcome MRSA. Carbenicillin, a β-lactam antibiotic, was used as an organic ligand that coordinates with Fe³⁺ to form a metal–carbenicillin framework to block the pores of the MSN. Furthermore, these β-lactamase inhibitor-loaded nanoantibiotics were stable under physiological conditions and could synchronously release antibiotic molecules and inhibitors at the bacterial infection site to achieve a better elimination of antibiotic resistant bacterial strains and biofilms. We confirmed that these β-lactamase inhibitor-loaded nanoantibiotics had better penetration depth into biofilms and an obvious effect on the inhibition of MRSA both in vitro and in vivo.

中文翻译：

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基于金属-卡宾西林骨架的纳米抗生素，具有增强的渗透性和对MRSA的高效抑制作用

控制抗生素耐药性的金黄色葡萄球菌（MRSA）感染的有效疗法的开发具有挑战性，因为抗生素可以通过某些酶（例如β-内酰胺酶）的产生而降解。此外，抗生素本身无法穿透由细胞外聚合物形成的生物膜的整个深度。基于纳米粒子的载体可以提供具有更好的生物膜渗透性的抗生素，从而抵抗细菌的耐药性。在这项研究中，我们描述了一种基于金属-卡尼西林骨架包被的介孔二氧化硅纳米粒子（MSN）来共同递送纳米抗生素的β-内酰胺抗生素和β-内酰胺酶抑制剂的通用方法，以克服MRSA。β-内酰胺抗生素羧苄青霉素被用作与铁配位的有机配体³⁺形成金属-碳青霉烯骨架，以堵塞MSN的孔。此外，这些负载有β-内酰胺酶抑制剂的纳米抗生素在生理条件下是稳定的，并且可以在细菌感染部位同步释放抗生素分子和抑制剂，从而更好地消除耐药菌菌株和生物膜。我们证实，这些β内酰胺酶抑制剂加载nanoantibiotics最好穿透深度生物膜和上MRSA的无论是在抑制的效果显着的体外和体内。