Lang Jiayan, Ma Xiaojing, Liu Sophie S, Streever Danielle L, Serota Max D, Franklin Trevor, Loew Ellis R, Yang Rong
Robert F. Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
These authors contributed equally to this work.
Nano Today. 2022 Dec;47. doi: 10.1016/j.nantod.2022.101672. Epub 2022 Nov 10.
Otitis media (OM) is the main reason for pediatric antibiotic prescriptions. The current treatment mandates a rigorous regimen of multidose antibiotics over 5-10 days. The systemic antibiotic exposure and often prematurely terminated treatment due to the challenge of drug administration to young patients are believed to breed antibiotic resistance. To address these challenges, we designed a local treatment that converted a metabolic product (HO) of an OM pathogen () into a potent antiseptic (HOBr), a reaction catalyzed by locally administered vanadium pentoxide nanowires. The therapeutic, HOBr, was only synthesized in the presence of the pathogen, enabling on-demand generation of therapeutics for OM treatment. Hypohalous acids are broad-spectrum and have a long history in general disinfection applications without breeding substantial drug resistance. A single dose of the nanowire formulation eradicated OM in a standard chinchilla model in 7 days with no observable tissue toxicity or negative impact on hearing sensitivity.
中耳炎(OM)是儿科抗生素处方的主要原因。目前的治疗要求在5至10天内严格使用多剂量抗生素。由于给年轻患者用药具有挑战性,全身抗生素暴露以及治疗常常过早终止,被认为会滋生抗生素耐药性。为应对这些挑战,我们设计了一种局部治疗方法,该方法将中耳炎病原体的一种代谢产物(HO)转化为一种强效防腐剂(HOBr),这一反应由局部施用的五氧化二钒纳米线催化。治疗剂HOBr仅在病原体存在时合成,能够按需生成用于中耳炎治疗的治疗剂。次卤酸具有广谱性,在一般消毒应用中有很长的历史,不会产生大量耐药性。在标准的栗鼠模型中,单剂量的纳米线制剂在7天内根除了中耳炎,没有观察到组织毒性或对听力敏感性的负面影响。