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Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids
[Image: see text] Glyco-decorated spherical nucleic acids (SNAs) may be attractive delivery vehicles, emphasizing the sugar-specific effect on the outer sphere of the construct and at the same time hiding unfavorable distribution properties of the loaded oligonucleotides. As examples of such nanopar...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778632/ https://www.ncbi.nlm.nih.gov/pubmed/34985282 http://dx.doi.org/10.1021/acs.bioconjchem.1c00539 |
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author | Tähtinen, Ville Gulumkar, Vijay Maity, Sajal K. Yliperttula, Ann-Mari Siekkinen, Saara Laine, Toni Lisitsyna, Ekaterina Haapalehto, Iida Viitala, Tapani Vuorimaa-Laukkanen, Elina Yliperttula, Marjo Virta, Pasi |
author_facet | Tähtinen, Ville Gulumkar, Vijay Maity, Sajal K. Yliperttula, Ann-Mari Siekkinen, Saara Laine, Toni Lisitsyna, Ekaterina Haapalehto, Iida Viitala, Tapani Vuorimaa-Laukkanen, Elina Yliperttula, Marjo Virta, Pasi |
author_sort | Tähtinen, Ville |
collection | PubMed |
description | [Image: see text] Glyco-decorated spherical nucleic acids (SNAs) may be attractive delivery vehicles, emphasizing the sugar-specific effect on the outer sphere of the construct and at the same time hiding unfavorable distribution properties of the loaded oligonucleotides. As examples of such nanoparticles, tripodal sugar constituents of bleomycin were synthesized and conjugated with a fluorescence-labeled antisense oligonucleotide (AON(ARV7)). Successive copper(I)-catalyzed azide-alkyne and strain-promoted alkyne-nitrone cycloadditions (SPANC) were utilized for the synthesis. Then, the glyco-AON(ARV7) conjugates were hybridized with complementary strands of a C(60)-based molecular spherical nucleic acid (i.e., a hybridization-mediated carrier). The formation and stability of these assembled glyco-decorated SNAs were evaluated by polyacrylamide gel electrophoresis (PAGE), UV melting profile analysis, and time-resolved fluorescence spectroscopy. Association constants were extracted from time-resolved fluorescence data. Preliminary cellular uptake experiments of the glyco-AON(ARV7) conjugates (120 nM solutions) and of the corresponding glyco-decorated SNAs (10 nM solutions) with human prostate cancer cells (PC3) showed an efficient uptake in each case. A marked variation in intracellular distribution was observed. |
format | Online Article Text |
id | pubmed-8778632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-87786322022-01-24 Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids Tähtinen, Ville Gulumkar, Vijay Maity, Sajal K. Yliperttula, Ann-Mari Siekkinen, Saara Laine, Toni Lisitsyna, Ekaterina Haapalehto, Iida Viitala, Tapani Vuorimaa-Laukkanen, Elina Yliperttula, Marjo Virta, Pasi Bioconjug Chem [Image: see text] Glyco-decorated spherical nucleic acids (SNAs) may be attractive delivery vehicles, emphasizing the sugar-specific effect on the outer sphere of the construct and at the same time hiding unfavorable distribution properties of the loaded oligonucleotides. As examples of such nanoparticles, tripodal sugar constituents of bleomycin were synthesized and conjugated with a fluorescence-labeled antisense oligonucleotide (AON(ARV7)). Successive copper(I)-catalyzed azide-alkyne and strain-promoted alkyne-nitrone cycloadditions (SPANC) were utilized for the synthesis. Then, the glyco-AON(ARV7) conjugates were hybridized with complementary strands of a C(60)-based molecular spherical nucleic acid (i.e., a hybridization-mediated carrier). The formation and stability of these assembled glyco-decorated SNAs were evaluated by polyacrylamide gel electrophoresis (PAGE), UV melting profile analysis, and time-resolved fluorescence spectroscopy. Association constants were extracted from time-resolved fluorescence data. Preliminary cellular uptake experiments of the glyco-AON(ARV7) conjugates (120 nM solutions) and of the corresponding glyco-decorated SNAs (10 nM solutions) with human prostate cancer cells (PC3) showed an efficient uptake in each case. A marked variation in intracellular distribution was observed. American Chemical Society 2022-01-05 2022-01-19 /pmc/articles/PMC8778632/ /pubmed/34985282 http://dx.doi.org/10.1021/acs.bioconjchem.1c00539 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Tähtinen, Ville Gulumkar, Vijay Maity, Sajal K. Yliperttula, Ann-Mari Siekkinen, Saara Laine, Toni Lisitsyna, Ekaterina Haapalehto, Iida Viitala, Tapani Vuorimaa-Laukkanen, Elina Yliperttula, Marjo Virta, Pasi Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids |
title | Assembly of Bleomycin Saccharide-Decorated Spherical
Nucleic Acids |
title_full | Assembly of Bleomycin Saccharide-Decorated Spherical
Nucleic Acids |
title_fullStr | Assembly of Bleomycin Saccharide-Decorated Spherical
Nucleic Acids |
title_full_unstemmed | Assembly of Bleomycin Saccharide-Decorated Spherical
Nucleic Acids |
title_short | Assembly of Bleomycin Saccharide-Decorated Spherical
Nucleic Acids |
title_sort | assembly of bleomycin saccharide-decorated spherical
nucleic acids |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778632/ https://www.ncbi.nlm.nih.gov/pubmed/34985282 http://dx.doi.org/10.1021/acs.bioconjchem.1c00539 |
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