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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-9609631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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