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Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers

Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known c...

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Autores principales: Márquez-Miranda, Valeria, Camarada, María Belén, Araya-Durán, Ingrid, Varas-Concha, Ignacio, Almonacid, Daniel Eduardo, González-Nilo, Fernando Danilo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575034/
https://www.ncbi.nlm.nih.gov/pubmed/26382062
http://dx.doi.org/10.1371/journal.pone.0138392
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author Márquez-Miranda, Valeria
Camarada, María Belén
Araya-Durán, Ingrid
Varas-Concha, Ignacio
Almonacid, Daniel Eduardo
González-Nilo, Fernando Danilo
author_facet Márquez-Miranda, Valeria
Camarada, María Belén
Araya-Durán, Ingrid
Varas-Concha, Ignacio
Almonacid, Daniel Eduardo
González-Nilo, Fernando Danilo
author_sort Márquez-Miranda, Valeria
collection PubMed
description Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers.
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spelling pubmed-45750342015-09-25 Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers Márquez-Miranda, Valeria Camarada, María Belén Araya-Durán, Ingrid Varas-Concha, Ignacio Almonacid, Daniel Eduardo González-Nilo, Fernando Danilo PLoS One Research Article Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. Public Library of Science 2015-09-18 /pmc/articles/PMC4575034/ /pubmed/26382062 http://dx.doi.org/10.1371/journal.pone.0138392 Text en © 2015 Márquez-Miranda et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Márquez-Miranda, Valeria
Camarada, María Belén
Araya-Durán, Ingrid
Varas-Concha, Ignacio
Almonacid, Daniel Eduardo
González-Nilo, Fernando Danilo
Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers
title Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers
title_full Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers
title_fullStr Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers
title_full_unstemmed Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers
title_short Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers
title_sort biomimetics: from bioinformatics to rational design of dendrimers as gene carriers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575034/
https://www.ncbi.nlm.nih.gov/pubmed/26382062
http://dx.doi.org/10.1371/journal.pone.0138392
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