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Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome

Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to t...

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Autores principales: Sendra, Luis, Miguel, Antonio, Navarro-Plaza, M. Carmen, Herrero, María José, de la Higuera, José, Cháfer-Pericás, Consuelo, Aznar, Elena, Marcos, M. Dolores, Martínez-Máñez, Ramón, Rojas, Luis Alfonso, Alemany, Ramón, Aliño, Salvador F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353451/
https://www.ncbi.nlm.nih.gov/pubmed/32560474
http://dx.doi.org/10.3390/nano10061183
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author Sendra, Luis
Miguel, Antonio
Navarro-Plaza, M. Carmen
Herrero, María José
de la Higuera, José
Cháfer-Pericás, Consuelo
Aznar, Elena
Marcos, M. Dolores
Martínez-Máñez, Ramón
Rojas, Luis Alfonso
Alemany, Ramón
Aliño, Salvador F.
author_facet Sendra, Luis
Miguel, Antonio
Navarro-Plaza, M. Carmen
Herrero, María José
de la Higuera, José
Cháfer-Pericás, Consuelo
Aznar, Elena
Marcos, M. Dolores
Martínez-Máñez, Ramón
Rojas, Luis Alfonso
Alemany, Ramón
Aliño, Salvador F.
author_sort Sendra, Luis
collection PubMed
description Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70–80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer.
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spelling pubmed-73534512020-07-15 Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome Sendra, Luis Miguel, Antonio Navarro-Plaza, M. Carmen Herrero, María José de la Higuera, José Cháfer-Pericás, Consuelo Aznar, Elena Marcos, M. Dolores Martínez-Máñez, Ramón Rojas, Luis Alfonso Alemany, Ramón Aliño, Salvador F. Nanomaterials (Basel) Article Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70–80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer. MDPI 2020-06-17 /pmc/articles/PMC7353451/ /pubmed/32560474 http://dx.doi.org/10.3390/nano10061183 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sendra, Luis
Miguel, Antonio
Navarro-Plaza, M. Carmen
Herrero, María José
de la Higuera, José
Cháfer-Pericás, Consuelo
Aznar, Elena
Marcos, M. Dolores
Martínez-Máñez, Ramón
Rojas, Luis Alfonso
Alemany, Ramón
Aliño, Salvador F.
Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
title Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
title_full Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
title_fullStr Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
title_full_unstemmed Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
title_short Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
title_sort gold nanoparticle-assisted virus formation by means of the delivery of an oncolytic adenovirus genome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353451/
https://www.ncbi.nlm.nih.gov/pubmed/32560474
http://dx.doi.org/10.3390/nano10061183
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