PDF(Pubmed)
Abstract：
DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures.
摘要：
DNA纳米结构长期以来一直被开发用于生物医学目的，但是它们在体内的受控递送对疾病疗法提出了重大挑战。我们以前报道过，几十和几百纳米尺度的DNA纳米结构显示出优先的肾脏排泄或肾脏滞留，允许对肾功能进行灵敏的评估和有效的保护，对单侧输尿管梗阻或急性肾损伤等事件的反应。受到积极成果的鼓舞，我们把注意力转向肝脏,特别针对明显缺乏DNA材料的器官，探索DNA纳米结构与肝脏之间的相互作用。通过PET成像,我们将SDF和M13鉴定为DNA纳米结构,在众多候选物中表现为在肝脏中显著积累.最初，我们调查并评估了它们的生物分布，毒性,和健康小鼠的免疫原性，建立正常小鼠DNA纳米结构的结构-功能关系。随后，我们采用肝脏缺血再灌注损伤(IRI)小鼠模型来验证SDF和M13在更具挑战性的病理条件下的纳米生物相互作用.M13不仅加剧了肝脏氧化损伤，而且还升高了局部细胞凋亡水平。相比之下,SDF表现出明显的清除肝脏氧化反应的能力，从而减轻肝细胞损伤。这些令人信服的结果强调了SDF作为肝脏相关病症的有希望的治疗剂的潜力。本文旨在阐明它们在肝损伤中的作用和机制，为DNA纳米结构的生物医学应用提供了新的视角。
