PD Chem ITech, Newcastle, WA, USA.
Department of Toxicology, Rutgers University, Piscataway, NJ, USA.
Biofouling. 2022 Jan;38(1):13-28. doi: 10.1080/08927014.2021.2008376. Epub 2021 Nov 28.
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).
等离子体引发的自由基聚合被用于工程化具有定制化学和物理性质的碳纳米粒子(CNPs)。经过表面改性后,CNPs 负载了一种高效的抗感染剂,称为无金属俄罗斯蜂胶乙醇提取物(MFRPEE),从而创造了基于纳米的药物传递系统(NBDDS)。MFRPEE 通过静电相互作用和氢键自然负载到接枝的 CNPs 上。当在最佳实验条件下构建时,NBDDS 在生理条件下稳定,并表现出比游离 MFRPEE 更强的抗生物膜活性。机制研究表明,NBDDS 的增强抗感染活性归因于接枝 CNPs 的表面化学修饰。更具体地说,接枝 CNPs 上的总正表面电荷源自共价结合到 CNPs 上的季铵聚合物刷,使 NBDDS 具有特异性靶向生物膜中带负电荷成分的能力。在研究 MFRPEE 从改性 CNPs 中的释放情况时,生物膜产生的酸性成分触发了与 NBDDS 结合的 MFRPEE 的释放。一旦游离形式,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 就不再能够保护生物膜内包裹的细菌免受抗感染剂的侵害。因此,暴露于 MFRPEE 会导致细菌细胞死亡和生物膜失活。本研究的结果开始研究 NBDDS 在治疗与医疗保健相关的感染(HCAIs)中的潜在应用。