Department of Cell Physiology & Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
BayRay Innovation Center, Shenzhen Bay Lab, Shenzhen, Guangdong Province, 518107, China.
Nat Commun. 2022 Jan 11;13(1):197. doi: 10.1038/s41467-021-27193-9.
To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn't alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (d ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.
为了从对细菌和哺乳动物细胞都具有敌意的化学基团中剖析纳米结构的抗生素作用，我们在此展示了由化学惰性的纳米硅球组成的纳米粒子夹聚合物刷（NPPB）的抗菌活性和细胞毒性，这些纳米硅球的直径经过系统变化，并通过共价键接枝上亲水聚合物刷，这些聚合物刷既无毒也无杀菌作用。将亲水聚合物组装成纳米结构的 NPPB 并不会改变它们与哺乳动物细胞的亲和性，但会改变它们对细菌的抗菌潜力，包括临床多药耐药菌株，这种潜力的改变取决于纳米颗粒的大小。获得的抗菌效力随着纳米颗粒的减小而增强，但随着纳米颗粒的增大而迅速减弱。我们确定了一个临界尺寸（d~50nm），只有低于这个尺寸，NPPB 才能将模拟细菌的细胞膜重塑为 2D 柱状相，这是细胞膜孔形成的缩影。这项研究阐明了纳米工程是一种可行的方法，可以开发出纳米抗生素，这些抗生素在接触时能杀死细菌，但被哺乳动物细胞吞噬时仍保持无毒。
