Abstract

Plasma-initiated free radical polymerization was used to engineer carbon nanoparticles (CNPs) with tailored chemical and physical properties. Following surface modification, CNPs were loaded with a highly effective anti-infection agent called metal-free Russian propolis ethanol extract (MFRPEE), thus, creating nano-based drug delivery systems (NBDDSs). The loading of MFRPEE onto grafted CNPs occurred naturally through both electrostatic interactions and hydrogen bonding. When constructed under optimal experimental conditions, the NBDDSs were stable under physiologic conditions, and demonstrated enhanced anti-biofilm activity when compared with free MFRPEE. Mechanistic studies revealed that the enhanced anti-infectious activity of the NBDDSs was attributed to the modified surface chemistry of grafted CNPs. More specifically, the overall positive surface charge on grafted CNPs, which stems from quaternary ammonium polymer brushes covalently bound to the CNPs, provides NBDDSs with the ability to specifically target negatively charged components of biofilms. When studying the release profile of MFRPEE from the modified CNPs, acidic components produced by a biofilm triggered the release of MFRPEE bound to the NBDDS. Once in its free form, the anti-infectious properties of MFRPEE became activated and damaged the extracellular polymeric matrix (EPM) of the biofilm. Once the architecture of the biofilm became compromised, the EPM was no longer capable of protecting the bacteria encapsulated within the biofilm from the anti-infectious agent. Consequently, exposure of bacteria to MFRPEE led to bacterial cell death and biofilm inactivation. The results obtained from this study begin to examine the potential application of NBDDSs for the treatment of healthcare-associated infections (HCAIs).

摘要

等离子体引发的自由基聚合用于设计具有定制化学和物理特性的碳纳米颗粒 (CNP)。经过表面改性后，CNPs 负载了一种称为无金属俄罗斯蜂胶乙醇提取物 (MFRPEE) 的高效抗感染剂，从而创建了纳米药物输送系统 (NBDDS)。MFRPEE 负载到接枝的 CNP 上是通过静电相互作用和氢键自然发生的。当在最佳实验条件下构建时，NBDDS 在生理条件下是稳定的，并且与游离 MFRPEE 相比表现出增强的抗生物膜活性。机理研究表明，NBDDS 增强的抗感染活性归因于接枝 CNP 的改性表面化学。进一步来说，嫁接的 CNP 上的整体正表面电荷（源于与 CNP 共价结合的季铵聚合物刷）为 NBDDS 提供了专门针对生物膜带负电成分的能力。在研究改性 CNP 的 MFRPEE 释放曲线时，生物膜产生的酸性成分触发了与 NBDDS 结合的 MFRPEE 的释放。一旦处于游离状态，MFRPEE 的抗感染特性就会被激活并破坏生物膜的细胞外聚合物基质 (EPM)。一旦生物膜的结构受到损害，EPM 就不再能够保护封装在生物膜内的细菌免受抗感染剂的侵害。因此，细菌暴露于 MFRPEE 会导致细菌细胞死亡和生物膜失活。