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Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs

The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polyme...

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Autores principales: Gomes dos Reis, Larissa, Lee, Wing-Hin, Svolos, Maree, Moir, Lyn Margaret, Jaber, Rima, Windhab, Norbert, Young, Paul Michael, Traini, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359528/
https://www.ncbi.nlm.nih.gov/pubmed/30609825
http://dx.doi.org/10.3390/pharmaceutics11010012
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author Gomes dos Reis, Larissa
Lee, Wing-Hin
Svolos, Maree
Moir, Lyn Margaret
Jaber, Rima
Windhab, Norbert
Young, Paul Michael
Traini, Daniela
author_facet Gomes dos Reis, Larissa
Lee, Wing-Hin
Svolos, Maree
Moir, Lyn Margaret
Jaber, Rima
Windhab, Norbert
Young, Paul Michael
Traini, Daniela
author_sort Gomes dos Reis, Larissa
collection PubMed
description The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic–co–glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs–DNA–CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%–15%) after 24 h of incubation and increase in autophagy, induced by NPs–DNA–CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs–DNA–CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs.
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spelling pubmed-63595282019-02-14 Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs Gomes dos Reis, Larissa Lee, Wing-Hin Svolos, Maree Moir, Lyn Margaret Jaber, Rima Windhab, Norbert Young, Paul Michael Traini, Daniela Pharmaceutics Article The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic–co–glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs–DNA–CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%–15%) after 24 h of incubation and increase in autophagy, induced by NPs–DNA–CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs–DNA–CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs. MDPI 2019-01-03 /pmc/articles/PMC6359528/ /pubmed/30609825 http://dx.doi.org/10.3390/pharmaceutics11010012 Text en © 2019 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
Gomes dos Reis, Larissa
Lee, Wing-Hin
Svolos, Maree
Moir, Lyn Margaret
Jaber, Rima
Windhab, Norbert
Young, Paul Michael
Traini, Daniela
Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
title Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
title_full Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
title_fullStr Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
title_full_unstemmed Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
title_short Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
title_sort nanotoxicologic effects of plga nanoparticles formulated with a cell-penetrating peptide: searching for a safe pdna delivery system for the lungs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359528/
https://www.ncbi.nlm.nih.gov/pubmed/30609825
http://dx.doi.org/10.3390/pharmaceutics11010012
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