Department of Biomedical Engineering, Particulate Fluids Processing Centre, University of Melbourne, Parkville, VIC 3010, Australia.
Nanoscale. 2019 Aug 8;11(31):14937-14951. doi: 10.1039/c9nr04424h.
The overuse of antibiotics has induced the rapid development of antibiotic resistance in bacteria. As a result, antibiotic efficacy has become limited, and infection with multidrug-resistant bacteria is considered to be one of the largest global human health threats. Consequently, new, effective and safe antimicrobial agents need to be developed urgently. One promising candidate to address this requirement is selenium nanoparticles (Se NPs), which are made from the essential dietary trace element Se and have antimicrobial activity against Gram-positive bacteria. The size of nanomaterials can strongly affect their biophysical properties and functions; however, the effects of the size of Se NPs on their antibacterial efficacy has not been systematically investigated. Therefore, in this work, spherical Se NPs ranging from 43 to 205 nm in diameter were fabricated, and their mammalian cytotoxicity and antibacterial activity as a function of their size were systematically studied. The antibacterial activity of the Se NPs was shown to be strongly size dependent, with 81 nm Se NPs showing the maximal growth inhibition and killing effect of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). The Se NPs were shown to have multi-modal mechanisms of action that depended on their size, including depleting internal ATP, inducing ROS production, and disrupting membrane potential. All the Se NPs were non-toxic towards mammalian cells up to 25 μg mL-1. Furthermore, the MIC value for the 81 nm particles produced in this research is 16 ± 7 μg mL-1, significantly lower than previously reported MIC values for Se NPs. This data illustrates that Se NP size is a facile yet critical and previously underappreciated parameter that can be tailored for maximal antimicrobial efficacy. We have identified that using Se NPs with a size of 81 nm and concentration of 10 μg mL-1 shows promise as a safe and efficient way to kill S. aureus without damaging mammalian cells.
抗生素的过度使用导致了细菌对抗生素耐药性的快速发展。结果，抗生素的疗效变得有限，而感染多重耐药菌被认为是对全球人类健康的最大威胁之一。因此，迫切需要开发新的、有效和安全的抗菌剂。一种有前途的候选药物是硒纳米粒子（Se NPs），它由必需的膳食微量元素硒制成，对革兰氏阳性菌具有抗菌活性。纳米材料的尺寸会强烈影响其生物物理特性和功能；然而，Se NPs 的尺寸对其抗菌功效的影响尚未得到系统研究。因此，在这项工作中，我们制备了直径从 43 到 205nm 的球形 Se NPs，并系统研究了它们的尺寸与其哺乳动物细胞毒性和抗菌活性之间的关系。研究表明，Se NPs 的抗菌活性强烈依赖于其尺寸，其中 81nm Se NPs 对耐甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）的生长抑制和杀伤作用最大。研究表明，Se NPs 具有多种作用模式，这些模式依赖于其尺寸，包括耗尽内部 ATP、诱导 ROS 产生和破坏膜电位。所有 Se NPs 在高达 25μg/mL 的浓度下对哺乳动物细胞均无毒性。此外，本研究中制备的 81nm 粒子的 MIC 值为 16±7μg/mL，明显低于之前报道的 Se NPs 的 MIC 值。这些数据表明，Se NP 的尺寸是一个简便但关键且以前被低估的参数，可以根据最大抗菌效果进行调整。我们已经确定，使用尺寸为 81nm 且浓度为 10μg/mL 的 Se NPs 具有作为一种安全有效的杀死金黄色葡萄球菌而不损伤哺乳动物细胞的方法的潜力。
