PDF(Pubmed)
Abstract：
Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.
摘要：
迫切需要针对难以治疗的细菌感染的新治疗策略，更快、更便宜的方法可能是重新利用现有的抗生素。纳米递送系统通过引导抗生素到达其靶标来增强抗生素的功效，增加感染部位的局部浓度。虽然最近描述的纳米递送系统是有前途的，它们通常不容易适应不同的目标，缺乏生物相容性或特异性。这里,纳米递送系统从噬菌体中获得靶向蛋白。噬菌体受体结合蛋白和细胞壁结合域与纳米颗粒结合,有针对性地运送利福平,亚胺培南,和氨苄青霉素对抗细菌病原体。它们对它们的靶标表现出极好的特异性，并积聚在感染部位以提供其抗生素有效载荷。此外，纳米递送系统比游离抗生素剂量高16至32倍更有效地抑制病原体感染.这项研究表明，噬菌体来源的靶向蛋白是指导纳米递送系统的有希望的候选物。他们的特殊性，可用性,和生物相容性使它们成为指导抗生素纳米递送系统的绝佳选择，这些系统迫切需要对抗难以治疗的感染。
