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Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids

pH-sensitive lipids represent a class of lipids that can be protonated and destabilized in acidic environments, as they become positively charged in response to low-pH conditions. They can be incorporated into lipidic nanoparticles such as liposomes, which are able to change their properties and all...

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Autores principales: Lado-Touriño, Isabel, Cerpa-Naranjo, Arisbel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003205/
https://www.ncbi.nlm.nih.gov/pubmed/36902063
http://dx.doi.org/10.3390/ijms24054632
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author Lado-Touriño, Isabel
Cerpa-Naranjo, Arisbel
author_facet Lado-Touriño, Isabel
Cerpa-Naranjo, Arisbel
author_sort Lado-Touriño, Isabel
collection PubMed
description pH-sensitive lipids represent a class of lipids that can be protonated and destabilized in acidic environments, as they become positively charged in response to low-pH conditions. They can be incorporated into lipidic nanoparticles such as liposomes, which are able to change their properties and allow specific drug delivery at the acidic conditions encountered in some pathological microenvironments. In this work, we used coarse-grained molecular-dynamic simulations to study the stability of neutral and charged lipid bilayers containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and various kinds of ISUCA ((F)2-(imidazol-1-yl)succinic acid)-derived lipids, which can act as pH-sensitive molecules. In order to explore such systems, we used a MARTINI-derived forcefield, previously parameterized using all-atom simulation results. We calculated the average area per lipid, the second-rank order parameter and the lipid diffusion coefficient of both lipid bilayers made of pure components and mixtures of lipids in different proportions, under neutral or acidic conditions. The results show that the use of ISUCA-derived lipids disturbs the lipid bilayer structure, with the effect being particularly marked under acidic conditions. Although more-in depth studies on these systems must be carried out, these initial results are encouraging and the lipids designed in this research could be a good basis for developing new pH-sensitive liposomes.
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spelling pubmed-100032052023-03-11 Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids Lado-Touriño, Isabel Cerpa-Naranjo, Arisbel Int J Mol Sci Article pH-sensitive lipids represent a class of lipids that can be protonated and destabilized in acidic environments, as they become positively charged in response to low-pH conditions. They can be incorporated into lipidic nanoparticles such as liposomes, which are able to change their properties and allow specific drug delivery at the acidic conditions encountered in some pathological microenvironments. In this work, we used coarse-grained molecular-dynamic simulations to study the stability of neutral and charged lipid bilayers containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and various kinds of ISUCA ((F)2-(imidazol-1-yl)succinic acid)-derived lipids, which can act as pH-sensitive molecules. In order to explore such systems, we used a MARTINI-derived forcefield, previously parameterized using all-atom simulation results. We calculated the average area per lipid, the second-rank order parameter and the lipid diffusion coefficient of both lipid bilayers made of pure components and mixtures of lipids in different proportions, under neutral or acidic conditions. The results show that the use of ISUCA-derived lipids disturbs the lipid bilayer structure, with the effect being particularly marked under acidic conditions. Although more-in depth studies on these systems must be carried out, these initial results are encouraging and the lipids designed in this research could be a good basis for developing new pH-sensitive liposomes. MDPI 2023-02-27 /pmc/articles/PMC10003205/ /pubmed/36902063 http://dx.doi.org/10.3390/ijms24054632 Text en © 2023 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
Lado-Touriño, Isabel
Cerpa-Naranjo, Arisbel
Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids
title Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids
title_full Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids
title_fullStr Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids
title_full_unstemmed Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids
title_short Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids
title_sort coarse-grained molecular dynamics of ph-sensitive lipids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003205/
https://www.ncbi.nlm.nih.gov/pubmed/36902063
http://dx.doi.org/10.3390/ijms24054632
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