Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Sci Adv. 2022 Jul 15;8(28):eabq2005. doi: 10.1126/sciadv.abq2005. Epub 2022 Jul 13.
Bacteriophages (phages) are widely explored as antimicrobials for treating infectious diseases due to their specificity and potency to infect and inhibit host bacteria. However, the application of phages to inhibit intracellular pathogens has been greatly restricted by inadequacy in cell entry and endosomal escape. Here, we describe the use of cationic polymers to selectively cap negatively charged phage head rather than positively charged tail by electrostatic interaction, resulting in charge-reversed phages with uninfluenced vitality. Given the positive surface charge and proton sponge effect of the nanocapping, capped phages are able to enter intestinal epithelial cells and subsequently escape from endosomes to lyse harbored pathogens. In a murine model of intestinal infection, oral ingestion of capped phages significantly reduces the translocation of pathogens to major organs, showing a remarkable inhibition efficacy. Our work proposes that simple synthetic nanocapping can manipulate phage bioactivity, offering a facile platform for preparing next-generation antimicrobials.
噬菌体（phages）因其特异性和对宿主细菌的感染和抑制能力而被广泛探索作为治疗传染病的抗菌药物。然而，噬菌体在抑制细胞内病原体方面的应用受到很大限制，因为它们不能进入细胞和从内体逃逸。在这里，我们描述了使用阳离子聚合物通过静电相互作用选择性地覆盖带负电荷的噬菌体头部而不是带正电荷的尾部，从而产生活力不受影响的电荷反转噬菌体。由于纳米帽的正表面电荷和质子海绵效应，带帽噬菌体能够进入肠道上皮细胞，并随后从内体逃逸以裂解携带的病原体。在肠道感染的小鼠模型中，口服摄入带帽噬菌体可显著减少病原体向主要器官的转移，显示出显著的抑制效果。我们的工作表明，简单的合成纳米帽可以操纵噬菌体的生物活性，为制备下一代抗菌药物提供了一个简便的平台。
