Controlled phage therapy by photothermal ablation of specific bacterial species using gold nanorods targeted by chimeric phages
Controlled phage therapy by photothermal ablation of specific bacterial species using gold nanorods targeted by chimeric phages
复制标题
DOI：
10.1073/pnas.1913234117
复制
发表时间：
2020-01-28
影响因子：
11.1
通讯作者：
Chen, Irene A.
中科院分区：
文献类型：
--
作者：
Peng, Huan;Borg, Raymond E.;Chen, Irene A.
使用噬菌体（antibacterial phages，简称噬菌体）进行抗菌治疗，以治疗耐药性感染，正受到越来越多的关注。噬菌体已经进化出多种机制来靶向其细菌宿主，例如高亲和力、环境适应性强的哈代受体结合蛋白。然而，传统的噬菌体疗法遭受多种挑战，这些挑战源于使用指数复制、进化的实体，其生物学未被完全表征（例如，潜在的基因转导）。为了解决这个问题，我们将纳米粒子结合到金纳米棒上，创造了一种可以在使用时被破坏的试剂（称为“phanorods”）。嵌合体基因被设计成特异性附着于几种革兰氏阴性生物，包括人类病原体大肠杆菌、铜绿假单胞菌和霍乱弧菌，以及植物病原体野油菜黄单胞菌。利用光热消融技术，生物结合显体可以选择性地靶向并杀死特定的细菌细胞。在近红外光的激发下，金纳米棒通过非辐射衰变途径释放能量，局部产生热量，有效地杀死目标细菌细胞。在铜绿假单胞菌生物膜的背景下突出了特异性，其中显象照射杀死细菌细胞，同时对上皮细胞造成最小的损伤。局部温度和粘度测量显示细菌的高度局部化和选择性消融。对phanorod的照射也破坏了噬菌体，防止了复制并降低了传统噬菌体治疗的潜在风险，同时能够控制剂量。phanorod策略将高度进化的靶向策略与金纳米棒的光热特性相结合，为系统性杀死细菌细胞创造了一个控制良好的平台。
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 receptorbinding 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.