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Polymers 2018, 10(12), 1342; https://doi.org/10.3390/polym10121342

Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules

1
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Center of Nanoscale Materials and Biointegration, Birmingham, AL 35294, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 November 2018 / Revised: 30 November 2018 / Accepted: 3 December 2018 / Published: 5 December 2018
(This article belongs to the Special Issue Interpolymer Complexes)
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Abstract

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. View Full-Text
Keywords: multilayer capsules; layer-by-layer; DNA; ultrasound; microcapsules; hydrogen-bonded; hydrogel multilayer capsules; layer-by-layer; DNA; ultrasound; microcapsules; hydrogen-bonded; hydrogel
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Alford, A.; Tucker, B.; Kozlovskaya, V.; Chen, J.; Gupta, N.; Caviedes, R.; Gearhart, J.; Graves, D.; Kharlampieva, E. Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules. Polymers 2018, 10, 1342.

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