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用于治疗急性肾衰竭的 DNA 折纸纳米结构

一项基于纳米技术的新研究为治疗急性肾损伤和衰竭带来了希望。

肾脏是重要的重要器官,在体内执行关键功能。 它从我们的血液中去除废物和多余的水,产生尿液,然后通过输尿管从肾脏流到膀胱。 这些由肌肉和食物正常分解而在我们体内产生的废物必须被有效地丢弃和排泄。

在急性 肾功能衰竭,现在称为急性肾损伤 (AKI) 含氮废物迅速积聚和尿量减少,即身体努力产生尿液。 这种情况发生在疾病发作的短时间内(几天甚至几小时),会导致严重的并发症。 AKI 的主要原因是氧化应激,这是由于含氧废物增加导致自由基和抗氧化防御之间的平衡受到干扰,从而对脂质、蛋白质和 的DNA. 这种情况会导致炎症并加重肾脏疾病。 那么患心血管疾病和癌症的几率就很高。 这就是为什么众所周知富含抗氧化剂的食物和补充剂可以防止含氧废物的有害影响。 当肾脏疾病严重时,需要补液和透析等支持疗法,甚至可能需要肾移植。 AKI 没有可用的治愈方法,因此每年造成数百万人死亡。

保护和治疗受伤的肾脏仍然是医学上的一个巨大挑战。 被认为是金标准的抗氧化药物 NAC(N-乙酰半胱氨酸)通常用于在手术过程中保护肾脏免受毒性,但这种药物的生物利用度较差,因此效果有限。

用于治疗的纳米技术方法

近几十年来,纳米技术在包括治疗在内的生物医学方法中的应用步伐加快。 但此类应用在治疗肾脏疾病方面表现出局限性。 在一项新研究中,来自美国和中国的科学家描述了一种阻止 AKI 并通过使用纳米技术治疗 AKI 的新方法,该技术涉及直径仅为十亿分之一米的微小自组装形式。 这些形状是使用纳米技术方法设计和开发的,称为“DNA折纸' 其中四个碱基配对 的DNA nucleotides is used to engineer and fabricate what is called 的DNA origami nanostructures (DONs). These nanostructures – either triangular, tubular or rectangular in shape – can be then used for performing various tasks inside the body. The architecture of such 纳米结构 非常适合生命系统,因为它们稳定且具有低毒性和免疫原性。

的DNA origami nanostructures self-assemble and latch onto different parts of the kidneys and form a protective layer around them. This has been seen when assessing their physiological distribution using quantitative imaging by positron emission tomography (PET). Their study is published in 自然生物医学工程. The group prepared various 的DNA origami structures and also used 无线电 labelling to study their behaviour in mouse kidney while analysing them using PET imaging. They were seen to accumulate in kidneys of healthy mice as well those who had AKI.

The study showed how 的DNA origami nanostructures act as a fast (within only 2 hours) and very active kidney protectant and were also therapeutic in relieving symptoms of AKI. Upon examination of their real-time distribution using PET scan it was see that rectangular nanostructures particularly were most successful in protecting kidneys in the same manner as a standard drug would. These structures track down oxygen-containing waste products and insulate the cells from damage due to oxidative stress. They help maintain balance of free radicals and anti-oxidant defences in and around the kidney reducing and alleviating oxidative stress which is the leading source and symptom of AKI. The measures taken by DONs stop the kidney disease to progress. DONs were tested both on living mice kidney and human embryonic kidney cells. These structures acted as a protective guard and improved kidney function in AKI as effectively as traditional drug therapies particularly NAC drug for AKI.

DNA 折纸结构持续存在于肾脏中,作者认为这是由于多种因素造成的,包括 DON 对消化酶的抵抗力以及它们避免免疫系统监视。 在生理上,通过观察血清肌酐和血尿素氮水平来评估肾功能的改善,很明显,与标准药物治疗相比,肾排泄功能有显着改善。

This multidisciplinary study combines expertise of nanomedicine and in-vivo imaging and is the first ever to investigate distribution of 的DNA nanostructures in a living system by live tracking their behaviour. DONs have low toxicity in main organs of the body making them ideally suited for clinical use in humans. This modern technology is a strong foundation which can provide localized protection to kidneys from AKI and can be used to design novel therapeutic approaches for treating AKI and other kidney diseases. A solution for kidney diseases could become a reality for patients suffering from acute kidney injury. The study adds to the potential of therapeutic programmable nanostructures which can be used for targeted drug delivery and organ and tissue repair in the body.

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{您可以通过单击下面引用来源列表中给出的 DOI 链接来阅读原始研究论文}

来源(S)

Jiang D et al. 2018. 的DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury. 自然生物医学工程. 2(1)。 https://doi.org/10.1038/s41551-018-0317-8

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赛欧团队
赛欧团队https://www.ScientificEuropean.co.uk
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