Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations

Oligopeptide end–modified poly(β-amino ester)s (OM-pBAEs) offer a means for the effective implementation of gene therapeutics in the near future. A fine-tuning of OM-pBAEs to meet application requirements is achieved by the proportional balance of oligopeptides used and provide gene carriers with hi...

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Detalles Bibliográficos
Autores: Navalón López, María, Dols-Perez, Aurora, Grijalvo, Santiago, Fornaguera, Cristina, Borrós, Salvador
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Ramon Llull (URL)
Repositorio:DAU Arxiu Digital de la Universitat Ramon Llull
OAI Identifier:oai:dau.url.edu:20.500.14342/4673
Acceso en línea:http://hdl.handle.net/20.500.14342/4673
https://doi.org/10.1039/D2NA00800A
Access Level:acceso abierto
Palabra clave:Oligopeptide end–modified poly(β-amino ester)s
Oligopeptides
Fluorescence resonance energy transfer
Amino acids
Higher adhesion properties
Pèptid
Transmissió d'energia de ressonància
Aminoàcids
Adherència
54
620
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spelling Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulationsNavalón López, MaríaDols-Perez, AuroraGrijalvo, SantiagoFornaguera, CristinaBorrós, SalvadorOligopeptide end–modified poly(β-amino ester)sOligopeptidesFluorescence resonance energy transferAmino acidsHigher adhesion propertiesPèptidTransmissió d'energia de ressonànciaAminoàcidsAdherència54620Oligopeptide end–modified poly(β-amino ester)s (OM-pBAEs) offer a means for the effective implementation of gene therapeutics in the near future. A fine-tuning of OM-pBAEs to meet application requirements is achieved by the proportional balance of oligopeptides used and provide gene carriers with high transfection efficacy, low toxicity, precise targeting, biocompatibility, and biodegradability. Understanding the influence and conformation of each building block at molecular and biological levels is therefore pivotal for further development and improvement of these gene carriers. Herein, we unmask the role of individual OM-pBAE components and their conformation in OM-pBAE/polynucleotide nanoparticles using a combination of fluorescence resonance energy transfer, enhanced darkfield spectral microscopy, atomic force microscopy, and microscale thermophoresis. We found that modifying the pBAE backbone with three end-terminal amino acids produces unique mechanical and physical properties for each combination. Higher adhesion properties are seen with arginine and lysine-based hybrid nanoparticles, while histidine provides an advantage in terms of construct stability. Our results shed light on the high potential of OM-pBAEs as gene delivery vehicles and provide insights into the influence of the nature of surface charges and the chemical nature of the pBAE modifications on their paths towards endocytosis, endosomal escape, and transfection.info:eu-repo/semantics/publishedVersionRoyal Society of ChemistryUniversitat Ramon Llull. IQS202420242023info:eu-repo/semantics/articlep.13application/pdfhttp://hdl.handle.net/20.500.14342/4673https://doi.org/10.1039/D2NA00800Areponame:DAU Arxiu Digital de la Universitat Ramon Llullinstname:Universitat Ramon Llull (URL)InglésNanoscale Advances 2023, 7 (6)info:eu-repo/grantAgreement/MINECO/PN I+D/RTI2018-094734-B-C22info:eu-repo/grantAgreement/MCI/PN I+D/PID2019-110210GB-I00info:eu-repo/grantAgreement/MCI/PN I+D/RTC2019-007260-1info:eu-repo/grantAgreement/MCI/PN I+D/PID2021-125910OB-I00info:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 1559info:eu-repo/grantAgreement/EC/H2020/Marie Skłodowska-Curieinfo:eu-repo/grantAgreement/MCI/ISCIII/CB06© L'autor/aAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:dau.url.edu:20.500.14342/46732026-06-21T06:40:37Z
dc.title.none.fl_str_mv Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
title Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
spellingShingle Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
Navalón López, María
Oligopeptide end–modified poly(β-amino ester)s
Oligopeptides
Fluorescence resonance energy transfer
Amino acids
Higher adhesion properties
Pèptid
Transmissió d'energia de ressonància
Aminoàcids
Adherència
54
620
title_short Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
title_full Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
title_fullStr Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
title_full_unstemmed Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
title_sort Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations
dc.creator.none.fl_str_mv Navalón López, María
Dols-Perez, Aurora
Grijalvo, Santiago
Fornaguera, Cristina
Borrós, Salvador
author Navalón López, María
author_facet Navalón López, María
Dols-Perez, Aurora
Grijalvo, Santiago
Fornaguera, Cristina
Borrós, Salvador
author_role author
author2 Dols-Perez, Aurora
Grijalvo, Santiago
Fornaguera, Cristina
Borrós, Salvador
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universitat Ramon Llull. IQS
dc.subject.none.fl_str_mv Oligopeptide end–modified poly(β-amino ester)s
Oligopeptides
Fluorescence resonance energy transfer
Amino acids
Higher adhesion properties
Pèptid
Transmissió d'energia de ressonància
Aminoàcids
Adherència
54
620
topic Oligopeptide end–modified poly(β-amino ester)s
Oligopeptides
Fluorescence resonance energy transfer
Amino acids
Higher adhesion properties
Pèptid
Transmissió d'energia de ressonància
Aminoàcids
Adherència
54
620
description Oligopeptide end–modified poly(β-amino ester)s (OM-pBAEs) offer a means for the effective implementation of gene therapeutics in the near future. A fine-tuning of OM-pBAEs to meet application requirements is achieved by the proportional balance of oligopeptides used and provide gene carriers with high transfection efficacy, low toxicity, precise targeting, biocompatibility, and biodegradability. Understanding the influence and conformation of each building block at molecular and biological levels is therefore pivotal for further development and improvement of these gene carriers. Herein, we unmask the role of individual OM-pBAE components and their conformation in OM-pBAE/polynucleotide nanoparticles using a combination of fluorescence resonance energy transfer, enhanced darkfield spectral microscopy, atomic force microscopy, and microscale thermophoresis. We found that modifying the pBAE backbone with three end-terminal amino acids produces unique mechanical and physical properties for each combination. Higher adhesion properties are seen with arginine and lysine-based hybrid nanoparticles, while histidine provides an advantage in terms of construct stability. Our results shed light on the high potential of OM-pBAEs as gene delivery vehicles and provide insights into the influence of the nature of surface charges and the chemical nature of the pBAE modifications on their paths towards endocytosis, endosomal escape, and transfection.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.14342/4673
https://doi.org/10.1039/D2NA00800A
url http://hdl.handle.net/20.500.14342/4673
https://doi.org/10.1039/D2NA00800A
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nanoscale Advances 2023, 7 (6)
info:eu-repo/grantAgreement/MINECO/PN I+D/RTI2018-094734-B-C22
info:eu-repo/grantAgreement/MCI/PN I+D/PID2019-110210GB-I00
info:eu-repo/grantAgreement/MCI/PN I+D/RTC2019-007260-1
info:eu-repo/grantAgreement/MCI/PN I+D/PID2021-125910OB-I00
info:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 1559
info:eu-repo/grantAgreement/EC/H2020/Marie Skłodowska-Curie
info:eu-repo/grantAgreement/MCI/ISCIII/CB06
dc.rights.none.fl_str_mv © L'autor/a
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © L'autor/a
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv p.13
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:DAU Arxiu Digital de la Universitat Ramon Llull
instname:Universitat Ramon Llull (URL)
instname_str Universitat Ramon Llull (URL)
reponame_str DAU Arxiu Digital de la Universitat Ramon Llull
collection DAU Arxiu Digital de la Universitat Ramon Llull
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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