Cargando…

In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions

In the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for in vivo gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpos...

Descripción completa

Detalles Bibliográficos
Autores principales: Messerschmidt, Victoria L., Chintapula, Uday, Bonetesta, Fabrizio, Laboy-Segarra, Samantha, Naderi, Amir, Nguyen, Kytai T., Cao, Hung, Mager, Edward, Lee, Juhyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906778/
https://www.ncbi.nlm.nih.gov/pubmed/35283767
http://dx.doi.org/10.3389/fphys.2022.819767
_version_ 1784665463148511232
author Messerschmidt, Victoria L.
Chintapula, Uday
Bonetesta, Fabrizio
Laboy-Segarra, Samantha
Naderi, Amir
Nguyen, Kytai T.
Cao, Hung
Mager, Edward
Lee, Juhyun
author_facet Messerschmidt, Victoria L.
Chintapula, Uday
Bonetesta, Fabrizio
Laboy-Segarra, Samantha
Naderi, Amir
Nguyen, Kytai T.
Cao, Hung
Mager, Edward
Lee, Juhyun
author_sort Messerschmidt, Victoria L.
collection PubMed
description In the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for in vivo gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpose of the current study was to deliver a Notch Intracellular Domain (NICD)-encoded plasmid via poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to investigate the toxic environmental side effects for an in vivo experiment. In addition, we demonstrated the target delivery to the endothelium, including the endocardial layer, which is challenging to manipulate gene expression for cardiac functions due to the beating heart and rapid blood pumping. For this study, we used a zebrafish animal model and exposed it to nanoparticles at varying concentrations to observe for specific malformations over time for toxic effects of PLGA nanoparticles as a delivery vehicle. Our nanoparticles caused significantly less malformations than the positive control, ZnO nanoparticles. Additionally, the NICD plasmid was successfully delivered by PLGA nanoparticles and significantly increased Notch signaling related genes. Furthermore, our image based deep-learning analysis approach evaluated that the antibody conjugated nanoparticles were successfully bound to the endocardium to overexpress Notch related genes and improve cardiac function such as ejection fraction, fractional shortening, and cardiac output. This research demonstrates that PLGA nanoparticle-mediated target delivery to upregulate Notch related genes which can be a potential therapeutic approach with minimum toxic effects.
format Online
Article
Text
id pubmed-8906778
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89067782022-03-10 In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions Messerschmidt, Victoria L. Chintapula, Uday Bonetesta, Fabrizio Laboy-Segarra, Samantha Naderi, Amir Nguyen, Kytai T. Cao, Hung Mager, Edward Lee, Juhyun Front Physiol Physiology In the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for in vivo gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpose of the current study was to deliver a Notch Intracellular Domain (NICD)-encoded plasmid via poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to investigate the toxic environmental side effects for an in vivo experiment. In addition, we demonstrated the target delivery to the endothelium, including the endocardial layer, which is challenging to manipulate gene expression for cardiac functions due to the beating heart and rapid blood pumping. For this study, we used a zebrafish animal model and exposed it to nanoparticles at varying concentrations to observe for specific malformations over time for toxic effects of PLGA nanoparticles as a delivery vehicle. Our nanoparticles caused significantly less malformations than the positive control, ZnO nanoparticles. Additionally, the NICD plasmid was successfully delivered by PLGA nanoparticles and significantly increased Notch signaling related genes. Furthermore, our image based deep-learning analysis approach evaluated that the antibody conjugated nanoparticles were successfully bound to the endocardium to overexpress Notch related genes and improve cardiac function such as ejection fraction, fractional shortening, and cardiac output. This research demonstrates that PLGA nanoparticle-mediated target delivery to upregulate Notch related genes which can be a potential therapeutic approach with minimum toxic effects. Frontiers Media S.A. 2022-02-23 /pmc/articles/PMC8906778/ /pubmed/35283767 http://dx.doi.org/10.3389/fphys.2022.819767 Text en Copyright © 2022 Messerschmidt, Chintapula, Bonetesta, Laboy-Segarra, Naderi, Nguyen, Cao, Mager and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Messerschmidt, Victoria L.
Chintapula, Uday
Bonetesta, Fabrizio
Laboy-Segarra, Samantha
Naderi, Amir
Nguyen, Kytai T.
Cao, Hung
Mager, Edward
Lee, Juhyun
In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions
title In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions
title_full In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions
title_fullStr In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions
title_full_unstemmed In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions
title_short In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions
title_sort in vivo evaluation of non-viral nicd plasmid-loaded plga nanoparticles in developing zebrafish to improve cardiac functions
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906778/
https://www.ncbi.nlm.nih.gov/pubmed/35283767
http://dx.doi.org/10.3389/fphys.2022.819767
work_keys_str_mv AT messerschmidtvictorial invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT chintapulauday invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT bonetestafabrizio invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT laboysegarrasamantha invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT naderiamir invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT nguyenkytait invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT caohung invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT mageredward invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions
AT leejuhyun invivoevaluationofnonviralnicdplasmidloadedplgananoparticlesindevelopingzebrafishtoimprovecardiacfunctions