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Triggered Rapid Degradation of Nanoparticles for Gene Delivery

Effective gene delivery tools offer the possibility of addressing multiple diseases; current strategies rely on viruses or polyplexes. Encapsulation of DNA within nanoparticles is an attractive alternative method for gene delivery. We investigated the use of our recently developed Logic Gate Nanopar...

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Autores principales: Morachis, José M., Mahmoud, Enas A., Sankaranarayanan, Jagadis, Almutairi, Adah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388356/
https://www.ncbi.nlm.nih.gov/pubmed/22778965
http://dx.doi.org/10.1155/2012/291219
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author Morachis, José M.
Mahmoud, Enas A.
Sankaranarayanan, Jagadis
Almutairi, Adah
author_facet Morachis, José M.
Mahmoud, Enas A.
Sankaranarayanan, Jagadis
Almutairi, Adah
author_sort Morachis, José M.
collection PubMed
description Effective gene delivery tools offer the possibility of addressing multiple diseases; current strategies rely on viruses or polyplexes. Encapsulation of DNA within nanoparticles is an attractive alternative method for gene delivery. We investigated the use of our recently developed Logic Gate Nanoparticle for gene delivery. The nanoparticles, composed of a dual pH response random copolymer (poly-β-aminoester ketal-2), can undergo a two-step “in series” response to endosomal pH. The first sep is a hydrophobic-hydrophilic switch, which is followed immediately by rapid degradation. Rapid fragmentation is known to increase cytoplasmic delivery from nanoparticles. Therefore, we hypothesized that our Logic Gate Nanoparticles would enable increased gene delivery and expression relative to nanoparticles that degrade more slowly such as PLGA-based nanoparticles. Passive nanoparticle entry into cells was demonstrated by delivering Cy5-labeled pDNA encoding EGFP into HCT116, a colon carcinoma cell line. Flow cytometry analysis showed that cells are positive for Cy5-DNA-nanoparticles and produced EGFP expression superior to PLGA nanoparticles. Inhibition of V-ATPases using bafilomycin A1 demonstrates that expression of EGFP is dependent on low endosomal pH. The advanced Logic Gate Nanoparticles offer new therapeutic possibilities in gene delivery and other applications where rapid release is important.
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spelling pubmed-33883562012-07-09 Triggered Rapid Degradation of Nanoparticles for Gene Delivery Morachis, José M. Mahmoud, Enas A. Sankaranarayanan, Jagadis Almutairi, Adah J Drug Deliv Research Article Effective gene delivery tools offer the possibility of addressing multiple diseases; current strategies rely on viruses or polyplexes. Encapsulation of DNA within nanoparticles is an attractive alternative method for gene delivery. We investigated the use of our recently developed Logic Gate Nanoparticle for gene delivery. The nanoparticles, composed of a dual pH response random copolymer (poly-β-aminoester ketal-2), can undergo a two-step “in series” response to endosomal pH. The first sep is a hydrophobic-hydrophilic switch, which is followed immediately by rapid degradation. Rapid fragmentation is known to increase cytoplasmic delivery from nanoparticles. Therefore, we hypothesized that our Logic Gate Nanoparticles would enable increased gene delivery and expression relative to nanoparticles that degrade more slowly such as PLGA-based nanoparticles. Passive nanoparticle entry into cells was demonstrated by delivering Cy5-labeled pDNA encoding EGFP into HCT116, a colon carcinoma cell line. Flow cytometry analysis showed that cells are positive for Cy5-DNA-nanoparticles and produced EGFP expression superior to PLGA nanoparticles. Inhibition of V-ATPases using bafilomycin A1 demonstrates that expression of EGFP is dependent on low endosomal pH. The advanced Logic Gate Nanoparticles offer new therapeutic possibilities in gene delivery and other applications where rapid release is important. Hindawi Publishing Corporation 2012 2012-06-19 /pmc/articles/PMC3388356/ /pubmed/22778965 http://dx.doi.org/10.1155/2012/291219 Text en Copyright © 2012 José M. Morachis et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Morachis, José M.
Mahmoud, Enas A.
Sankaranarayanan, Jagadis
Almutairi, Adah
Triggered Rapid Degradation of Nanoparticles for Gene Delivery
title Triggered Rapid Degradation of Nanoparticles for Gene Delivery
title_full Triggered Rapid Degradation of Nanoparticles for Gene Delivery
title_fullStr Triggered Rapid Degradation of Nanoparticles for Gene Delivery
title_full_unstemmed Triggered Rapid Degradation of Nanoparticles for Gene Delivery
title_short Triggered Rapid Degradation of Nanoparticles for Gene Delivery
title_sort triggered rapid degradation of nanoparticles for gene delivery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388356/
https://www.ncbi.nlm.nih.gov/pubmed/22778965
http://dx.doi.org/10.1155/2012/291219
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