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Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids

Spherical nucleic acids (SNAs)—nanostructures, consisting of a nanoparticle core densely functionalized with a shell of short oligonucleotide strands—are a rapidly emerging class of nanoparticle-based therapeutics with unique properties and specific applications as drug and nucleic acid delivery and...

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Autores principales: Dimitrov, Erik, Toncheva-Moncheva, Natalia, Bakardzhiev, Pavel, Forys, Aleksander, Doumanov, Jordan, Mladenova, Kirilka, Petrova, Svetla, Trzebicka, Barbara, Rangelov, Stanislav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609631/
https://www.ncbi.nlm.nih.gov/pubmed/36296836
http://dx.doi.org/10.3390/nano12203645
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author Dimitrov, Erik
Toncheva-Moncheva, Natalia
Bakardzhiev, Pavel
Forys, Aleksander
Doumanov, Jordan
Mladenova, Kirilka
Petrova, Svetla
Trzebicka, Barbara
Rangelov, Stanislav
author_facet Dimitrov, Erik
Toncheva-Moncheva, Natalia
Bakardzhiev, Pavel
Forys, Aleksander
Doumanov, Jordan
Mladenova, Kirilka
Petrova, Svetla
Trzebicka, Barbara
Rangelov, Stanislav
author_sort Dimitrov, Erik
collection PubMed
description Spherical nucleic acids (SNAs)—nanostructures, consisting of a nanoparticle core densely functionalized with a shell of short oligonucleotide strands—are a rapidly emerging class of nanoparticle-based therapeutics with unique properties and specific applications as drug and nucleic acid delivery and gene regulation materials. In this contribution, we report on the preparation of hollow SNA nanoconstructs by co-assembly of an originally synthesized nucleolipid—a hybrid biomacromolecule, composed of a lipidic residue, covalently linked to a DNA oligonucleotide strand—with other lipids. The nucleolipid was synthesized via a click chemistry approach employing initiator-free, UV light-induced thiol-ene coupling of appropriately functionalized intermediates, performed in mild conditions using a custom-made UV light-emitting device. The SNA nanoconstructs were of a vesicular structure consisting of a self-closed bilayer membrane in which the nucleolipid was intercalated via its lipid–mimetic residue. They were in the lower nanometer size range, moderately negatively charged, and were found to carry thousands of oligonucleotide strands per particle, corresponding to a grafting density comparable to that of other SNA structures. The surface density of the strands on the bilayer implied that they adopted an unextended conformation. We demonstrated that preformed vesicular structures could be successfully loaded with either hydrophilic or hydrophobic dyes.
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spelling pubmed-96096312022-10-28 Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids Dimitrov, Erik Toncheva-Moncheva, Natalia Bakardzhiev, Pavel Forys, Aleksander Doumanov, Jordan Mladenova, Kirilka Petrova, Svetla Trzebicka, Barbara Rangelov, Stanislav Nanomaterials (Basel) Communication Spherical nucleic acids (SNAs)—nanostructures, consisting of a nanoparticle core densely functionalized with a shell of short oligonucleotide strands—are a rapidly emerging class of nanoparticle-based therapeutics with unique properties and specific applications as drug and nucleic acid delivery and gene regulation materials. In this contribution, we report on the preparation of hollow SNA nanoconstructs by co-assembly of an originally synthesized nucleolipid—a hybrid biomacromolecule, composed of a lipidic residue, covalently linked to a DNA oligonucleotide strand—with other lipids. The nucleolipid was synthesized via a click chemistry approach employing initiator-free, UV light-induced thiol-ene coupling of appropriately functionalized intermediates, performed in mild conditions using a custom-made UV light-emitting device. The SNA nanoconstructs were of a vesicular structure consisting of a self-closed bilayer membrane in which the nucleolipid was intercalated via its lipid–mimetic residue. They were in the lower nanometer size range, moderately negatively charged, and were found to carry thousands of oligonucleotide strands per particle, corresponding to a grafting density comparable to that of other SNA structures. The surface density of the strands on the bilayer implied that they adopted an unextended conformation. We demonstrated that preformed vesicular structures could be successfully loaded with either hydrophilic or hydrophobic dyes. MDPI 2022-10-18 /pmc/articles/PMC9609631/ /pubmed/36296836 http://dx.doi.org/10.3390/nano12203645 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Dimitrov, Erik
Toncheva-Moncheva, Natalia
Bakardzhiev, Pavel
Forys, Aleksander
Doumanov, Jordan
Mladenova, Kirilka
Petrova, Svetla
Trzebicka, Barbara
Rangelov, Stanislav
Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids
title Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids
title_full Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids
title_fullStr Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids
title_full_unstemmed Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids
title_short Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids
title_sort original synthesis of a nucleolipid for preparation of vesicular spherical nucleic acids
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609631/
https://www.ncbi.nlm.nih.gov/pubmed/36296836
http://dx.doi.org/10.3390/nano12203645
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