Cargando…

Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects

Gene therapy and optogenetics are becoming promising tools for treating several nervous system pathologies. Currently, most of these approaches use viral vectors to transport the genetic material inside the cells, but viruses present some potential risks, such as marked immunogenicity, insertional m...

Descripción completa

Detalles Bibliográficos
Autores principales: Celdrán, José David, Humphreys, Lawrence, González, Desirée, Soto-Sánchez, Cristina, Martínez-Navarrete, Gema, Maldonado, Iván, Gallego, Idoia, Villate-Beitia, Ilia, Sainz-Ramos, Myriam, Puras, Gustavo, Pedraz, José Luis, Fernández, Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384779/
https://www.ncbi.nlm.nih.gov/pubmed/37514046
http://dx.doi.org/10.3390/pharmaceutics15071860
_version_ 1785081241101402112
author Celdrán, José David
Humphreys, Lawrence
González, Desirée
Soto-Sánchez, Cristina
Martínez-Navarrete, Gema
Maldonado, Iván
Gallego, Idoia
Villate-Beitia, Ilia
Sainz-Ramos, Myriam
Puras, Gustavo
Pedraz, José Luis
Fernández, Eduardo
author_facet Celdrán, José David
Humphreys, Lawrence
González, Desirée
Soto-Sánchez, Cristina
Martínez-Navarrete, Gema
Maldonado, Iván
Gallego, Idoia
Villate-Beitia, Ilia
Sainz-Ramos, Myriam
Puras, Gustavo
Pedraz, José Luis
Fernández, Eduardo
author_sort Celdrán, José David
collection PubMed
description Gene therapy and optogenetics are becoming promising tools for treating several nervous system pathologies. Currently, most of these approaches use viral vectors to transport the genetic material inside the cells, but viruses present some potential risks, such as marked immunogenicity, insertional mutagenesis, and limited insert gene size. In this framework, non-viral nanoparticles, such as niosomes, are emerging as possible alternative tools to deliver genetic material, avoiding the aforementioned problems. To determine their suitability as vectors for optogenetic therapies in this work, we tested three different niosome formulations combined with three optogenetic plasmids in rat cortical neurons in vitro. All niosomes tested successfully expressed optogenetic channels, which were dependent on the ratio of niosome to plasmid, with higher concentrations yielding higher expression rates. However, we found changes in the dendritic morphology and electrophysiological properties of transfected cells, especially when we used higher concentrations of niosomes. Our results highlight the potential use of niosomes for optogenetic applications and suggest that special care must be taken to achieve an optimal balance of niosomes and nucleic acids to achieve the therapeutic effects envisioned by these technologies.
format Online
Article
Text
id pubmed-10384779
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103847792023-07-30 Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects Celdrán, José David Humphreys, Lawrence González, Desirée Soto-Sánchez, Cristina Martínez-Navarrete, Gema Maldonado, Iván Gallego, Idoia Villate-Beitia, Ilia Sainz-Ramos, Myriam Puras, Gustavo Pedraz, José Luis Fernández, Eduardo Pharmaceutics Article Gene therapy and optogenetics are becoming promising tools for treating several nervous system pathologies. Currently, most of these approaches use viral vectors to transport the genetic material inside the cells, but viruses present some potential risks, such as marked immunogenicity, insertional mutagenesis, and limited insert gene size. In this framework, non-viral nanoparticles, such as niosomes, are emerging as possible alternative tools to deliver genetic material, avoiding the aforementioned problems. To determine their suitability as vectors for optogenetic therapies in this work, we tested three different niosome formulations combined with three optogenetic plasmids in rat cortical neurons in vitro. All niosomes tested successfully expressed optogenetic channels, which were dependent on the ratio of niosome to plasmid, with higher concentrations yielding higher expression rates. However, we found changes in the dendritic morphology and electrophysiological properties of transfected cells, especially when we used higher concentrations of niosomes. Our results highlight the potential use of niosomes for optogenetic applications and suggest that special care must be taken to achieve an optimal balance of niosomes and nucleic acids to achieve the therapeutic effects envisioned by these technologies. MDPI 2023-07-01 /pmc/articles/PMC10384779/ /pubmed/37514046 http://dx.doi.org/10.3390/pharmaceutics15071860 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
Celdrán, José David
Humphreys, Lawrence
González, Desirée
Soto-Sánchez, Cristina
Martínez-Navarrete, Gema
Maldonado, Iván
Gallego, Idoia
Villate-Beitia, Ilia
Sainz-Ramos, Myriam
Puras, Gustavo
Pedraz, José Luis
Fernández, Eduardo
Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
title Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
title_full Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
title_fullStr Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
title_full_unstemmed Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
title_short Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
title_sort assessment of different niosome formulations for optogenetic applications: morphological and electrophysiological effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384779/
https://www.ncbi.nlm.nih.gov/pubmed/37514046
http://dx.doi.org/10.3390/pharmaceutics15071860
work_keys_str_mv AT celdranjosedavid assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT humphreyslawrence assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT gonzalezdesiree assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT sotosanchezcristina assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT martineznavarretegema assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT maldonadoivan assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT gallegoidoia assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT villatebeitiailia assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT sainzramosmyriam assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT purasgustavo assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT pedrazjoseluis assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects
AT fernandezeduardo assessmentofdifferentniosomeformulationsforoptogeneticapplicationsmorphologicalandelectrophysiologicaleffects