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Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation

Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymer–oligonucleotide conjugates of different arc...

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Autores principales: Kalinova, Radostina, Mladenova, Kirilka, Petrova, Svetla, Doumanov, Jordan, Dimitrov, Ivaylo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786340/
https://www.ncbi.nlm.nih.gov/pubmed/36556721
http://dx.doi.org/10.3390/ma15248917
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author Kalinova, Radostina
Mladenova, Kirilka
Petrova, Svetla
Doumanov, Jordan
Dimitrov, Ivaylo
author_facet Kalinova, Radostina
Mladenova, Kirilka
Petrova, Svetla
Doumanov, Jordan
Dimitrov, Ivaylo
author_sort Kalinova, Radostina
collection PubMed
description Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymer–oligonucleotide conjugates of different architecture and to evaluate the possibility of forming SNAs with biodegradable cores. Initially, two types of azide (multi)functional polyester-based (co)polymers were successfully synthesized and characterized. In the next step, short oligonucleotide strands were attached to the polymer chains applying the highly efficient and metal-free “click” reaction, thus forming conjugates with block or graft architecture. Both conjugates spontaneously self-assembled in aqueous media forming nanosized SNAs with a biodegradable polyester core and a surface of oligonucleotide chains as evidenced from dynamic and electrophoretic light scattering measurements. The nano-assemblies were in vitro evaluated for potential cytotoxicity. Furthermore, the interactions of the newly synthesized SNAs with membrane lipids were studied. The preliminary results indicate that both types of polymer-based SNAs are good candidates for potential application in gene therapy and that it is worth to be further evaluated.
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spelling pubmed-97863402022-12-24 Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation Kalinova, Radostina Mladenova, Kirilka Petrova, Svetla Doumanov, Jordan Dimitrov, Ivaylo Materials (Basel) Article Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymer–oligonucleotide conjugates of different architecture and to evaluate the possibility of forming SNAs with biodegradable cores. Initially, two types of azide (multi)functional polyester-based (co)polymers were successfully synthesized and characterized. In the next step, short oligonucleotide strands were attached to the polymer chains applying the highly efficient and metal-free “click” reaction, thus forming conjugates with block or graft architecture. Both conjugates spontaneously self-assembled in aqueous media forming nanosized SNAs with a biodegradable polyester core and a surface of oligonucleotide chains as evidenced from dynamic and electrophoretic light scattering measurements. The nano-assemblies were in vitro evaluated for potential cytotoxicity. Furthermore, the interactions of the newly synthesized SNAs with membrane lipids were studied. The preliminary results indicate that both types of polymer-based SNAs are good candidates for potential application in gene therapy and that it is worth to be further evaluated. MDPI 2022-12-13 /pmc/articles/PMC9786340/ /pubmed/36556721 http://dx.doi.org/10.3390/ma15248917 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 Article
Kalinova, Radostina
Mladenova, Kirilka
Petrova, Svetla
Doumanov, Jordan
Dimitrov, Ivaylo
Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
title Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
title_full Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
title_fullStr Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
title_full_unstemmed Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
title_short Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation
title_sort nanoarchitectonics of spherical nucleic acids with biodegradable polymer cores: synthesis and evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786340/
https://www.ncbi.nlm.nih.gov/pubmed/36556721
http://dx.doi.org/10.3390/ma15248917
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