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Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

BACKGROUND: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this...

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Autores principales: Palombarini, Federica, Masciarelli, Silvia, Incocciati, Alessio, Liccardo, Francesca, Di Fabio, Elisa, Iazzetti, Antonia, Fabrizi, Giancarlo, Fazi, Francesco, Macone, Alberto, Bonamore, Alessandra, Boffi, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190868/
https://www.ncbi.nlm.nih.gov/pubmed/34107976
http://dx.doi.org/10.1186/s12951-021-00921-5
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author Palombarini, Federica
Masciarelli, Silvia
Incocciati, Alessio
Liccardo, Francesca
Di Fabio, Elisa
Iazzetti, Antonia
Fabrizi, Giancarlo
Fazi, Francesco
Macone, Alberto
Bonamore, Alessandra
Boffi, Alberto
author_facet Palombarini, Federica
Masciarelli, Silvia
Incocciati, Alessio
Liccardo, Francesca
Di Fabio, Elisa
Iazzetti, Antonia
Fabrizi, Giancarlo
Fazi, Francesco
Macone, Alberto
Bonamore, Alessandra
Boffi, Alberto
author_sort Palombarini, Federica
collection PubMed
description BACKGROUND: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. RESULTS: Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. CONCLUSION: The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00921-5.
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spelling pubmed-81908682021-06-10 Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells Palombarini, Federica Masciarelli, Silvia Incocciati, Alessio Liccardo, Francesca Di Fabio, Elisa Iazzetti, Antonia Fabrizi, Giancarlo Fazi, Francesco Macone, Alberto Bonamore, Alessandra Boffi, Alberto J Nanobiotechnology Research BACKGROUND: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. RESULTS: Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. CONCLUSION: The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00921-5. BioMed Central 2021-06-09 /pmc/articles/PMC8190868/ /pubmed/34107976 http://dx.doi.org/10.1186/s12951-021-00921-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Palombarini, Federica
Masciarelli, Silvia
Incocciati, Alessio
Liccardo, Francesca
Di Fabio, Elisa
Iazzetti, Antonia
Fabrizi, Giancarlo
Fazi, Francesco
Macone, Alberto
Bonamore, Alessandra
Boffi, Alberto
Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
title Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
title_full Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
title_fullStr Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
title_full_unstemmed Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
title_short Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
title_sort self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190868/
https://www.ncbi.nlm.nih.gov/pubmed/34107976
http://dx.doi.org/10.1186/s12951-021-00921-5
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