Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules
Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules
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DOI：
10.3390/polym10121342
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发表时间：
2018-12-01
期刊：
影响因子：
5
通讯作者：
Kharlampieva, Eugenia
中科院分区：
文献类型：
--
作者：
Alford, Aaron;Tucker, Brenna;Kharlampieva, Eugenia
核酸疗法有可能成为最有效的疾病治疗策略，因为它们对高度特异的生物过程进行编码的内在精确度和选择性。然而，任何类型的自由服用的核酸都会被体内的一系列防御机制迅速摧毁或变得惰性。在这项工作中，我们通过制备负载7 kDa G-四链DNA的刺激响应性聚甲基丙烯酸/聚(N-乙烯基吡咯烷酮)(PMAA/PVPON)(N)多层水凝胶胶囊来应对将核酸用作药物的挑战。这些胶囊被证明可以根据需要释放他们的DNA货物，以回应酶和超声波(US)引发的降解。G-四链体所采用的独特结构对其生物学功能是必不可少的，我们表明，微囊的控制释放保留了我们研究中使用的寡核苷酸的篮子构象。我们还发现，(PMAA/PVPON)多层水凝胶胶囊可以包裹和释放450 kDa的双链DNA。这两种寡核苷酸在多层水凝胶微囊中的包封和释放方法可用于创建涉及敏感生物分子控制传递的新治疗策略的方法学。我们的研究为设计DNA疫苗和药物的有效载体提供了一种有希望的方法学，可用于未来广泛的免疫治疗、癌症治疗和/或组织再生治疗。
Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)(n) multilayer hydrogel capsules loaded with 7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release 450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.