DNA nanoparticles for ophthalmic drug delivery
DNA nanoparticles for ophthalmic drug delivery
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DOI：
10.1016/j.biomaterials.2017.11.046
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发表时间：
2018-03-01
期刊：
影响因子：
14
通讯作者：
Herrmann, Andreas
中科院分区：
文献类型：
--
作者：
de Vries, Jan Willem;Schnichels, Sven;Herrmann, Andreas
核酸是构建纳米尺度物体的非常有吸引力的构件，在药物递送领域具有巨大的潜在应用，其中多功能纳米颗粒（NPs）发挥着关键作用。DNA纳米技术的一个机会在于眼科疾病的治疗，因为滴眼液的功效因药物在眼睛表面的短存活时间而受损。因此，眼部治疗剂的局部施用需要高药物剂量和频繁施用，仍然很少提供高生物利用度。为了克服这些缺点，我们介绍了一种新的和通用的载体系统，是基于DNA纳米技术。无毒的脂质修饰的DNA链（在5'端具有4个脂质修饰的胸腺嘧啶的12聚体）形成均匀的NP（胶束），其粘附于角膜表面延长的时间段。在一个单一的自组装步骤中，它们可以通过与适体杂交来装备不同的药物。DNA NP的长存活时间可以转化为改善的功效。它们的功能已在多个离体实验和体内动物模型中得到证实。最后，证实NP甚至适用于人体组织。(C)2017爱思唯尔有限公司版权所有
Nucleic acids represent very appealing building blocks for the construction of nano-scaled objects with great potential applications in the field of drug delivery where multifunctional nanoparticles (NPs) play a pivotal role. One opportunity for DNA nanotechnology lies in the treatment of ophthalmic diseases as the efficacy of eye drops is impaired by the short survival time of the drug on the eye surface. As a consequence, topical administration of ocular therapeutics requires high drug doses and frequent administration, still rarely providing high bioavailability. To overcome these shortcomings we introduce a novel and general carrier system that is based on DNA nanotechnology. Non-toxic, lipid-modified DNA strands (12mers with 4 lipid modified thymines at the 5' end) form uniform NPs (micelles), which adhere to the corneal surface for extended periods of time. In a single self-assembly step they can be equipped with different drugs by hybridization with an aptamer. The long survival times of DNA NPs can be translated into improved efficacy. Their functionality was demonstrated in several ex-vivo experiments and in an in-vivo animal model. Finally, the NPs were confirmed to be applicable even for human tissue. (C) 2017 Elsevier Ltd. All rights reserved.