The use of bacteriophages (phages) for antibacterial therapy is under increasing consideration to treat antimicrobial-resistant infections. Phages have evolved multiple mechanisms to target their bacterial hosts, such as high-affinity, environmentally hardy receptor-binding proteins. However, traditional phage therapy suffers from multiple challenges stemming from the use of an exponentially replicating, evolving entity whose biology is not fully characterized (e.g., potential gene transduction). To address this problem, we conjugate the phages to gold nanorods, creating a reagent that can be destroyed upon use (termed "phanorods"). Chimeric phages were engineered to attach specifically to several Gram-negative organisms, including the human pathogens Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae, and the plant pathogen Xanthomonas campestris The bioconjugated phanorods could selectively target and kill specific bacterial cells using photothermal ablation. Following excitation by near-infrared light, gold nanorods release energy through nonradiative decay pathways, locally generating heat that efficiently kills targeted bacterial cells. Specificity was highlighted in the context of a P. aeruginosa biofilm, in which phanorod irradiation killed bacterial cells while causing minimal damage to epithelial cells. Local temperature and viscosity measurements revealed highly localized and selective ablation of the bacteria. Irradiation of the phanorods also destroyed the phages, preventing replication and reducing potential risks of traditional phage therapy while enabling control over dosing. The phanorod strategy integrates the highly evolved targeting strategies of phages with the photothermal properties of gold nanorods, creating a well-controlled platform for systematic killing of bacterial cells.

中文翻译：

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使用嵌合噬菌体靶向的金纳米棒，通过光热消融特定细菌种类来控制噬菌体疗法。

人们越来越多地考虑使用噬菌体（噬菌体）进行抗菌治疗，以治疗耐药性感染。噬菌体已经进化出多种机制来靶向它们的细菌宿主，例如高亲和力、耐环境的受体结合蛋白。然而，传统的噬菌体疗法面临着多重挑战，这些挑战源于使用一种指数复制、进化的实体，其生物学特征尚未完全确定（例如，潜在的基因转导）。为了解决这个问题，我们将噬菌体与金纳米棒结合，创造了一种可以在使用时被破坏的试剂（称为“幻影棒”）。嵌合噬菌体被设计为专门附着在几种革兰氏阴性生物体上，包括人类病原体大肠杆菌、铜绿假单胞菌和霍乱弧菌，和植物病原体野油菜黄单胞菌生物结合的显影棒可以使用光热消融选择性地靶向并杀死特定的细菌细胞。在近红外光激发后，金纳米棒通过非辐射衰变途径释放能量，局部产生热量，有效杀死目标细菌细胞。在铜绿假单胞菌生物膜的背景下突出了特异性，其中 phanorod 辐射杀死细菌细胞，同时对上皮细胞造成最小损伤。局部温度和粘度测量显示细菌高度局部化和选择性消融。显影体的辐照也破坏了噬菌体，防止复制并降低传统噬菌体疗法的潜​​在风险，同时能够控制剂量。