A light-triggerable nanoparticle library for the controlled release of non-coding RNAs

Detalhes bibliográficos
Autor(a) principal: Josephine, Blersch
Data de Publicação: 2019
Outros Autores: Vitor, Francisco, Rebelo, Catarina, Adrian, Jimenez-Balsa, Antunes, Helena, Carlo, Gonzato, Pinto, Sandra, Simões, Susana, Klaus, Liedl, Karsten, Haupt, Ferreira, Lino
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/88171
https://doi.org/10.1002/anie.201911398
Resumo: RNA-based therapies offer a wide range of therapeutic interventions including for the treatment of skin diseases; however, the strategies to deliver efficiently these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we synthesized a triggerable polymeric nanoparticle (NP) library composed by 160 formulations, presenting physico-chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500%) than commercial Lipofectamine in gene knockdown activity. These formulations had differential internalization by skin cells and the endosomal escape was rapid (minutes range) as shown by the recruitment of galectin-8. The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA-150-5p healed faster than wounds treated with scramble miRNA. Light-activatable NPs offer a new strategy to deliver topically non-coding RNAs.
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spelling A light-triggerable nanoparticle library for the controlled release of non-coding RNAsRNA-based therapies offer a wide range of therapeutic interventions including for the treatment of skin diseases; however, the strategies to deliver efficiently these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we synthesized a triggerable polymeric nanoparticle (NP) library composed by 160 formulations, presenting physico-chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500%) than commercial Lipofectamine in gene knockdown activity. These formulations had differential internalization by skin cells and the endosomal escape was rapid (minutes range) as shown by the recruitment of galectin-8. The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA-150-5p healed faster than wounds treated with scramble miRNA. Light-activatable NPs offer a new strategy to deliver topically non-coding RNAs.ERA Chair project (ERA@UC, ref:669088) through EU Horizon 2020 program, the POCI-01-0145-FEDER-016390 (acronym: CANCEL STEM) and POCI-01- 0145-FEDER-029414 (acronym: LIghtBRARY) projects through Compete 2020 and FCT programs. NMR data was collected at the UC-NMR facility which is supported in part by FEDER – European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT62- FEDER-002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN).Wiley2019-11-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/88171http://hdl.handle.net/10316/88171https://doi.org/10.1002/anie.201911398enghttps://onlinelibrary.wiley.com/doi/10.1002/anie.201911398Josephine, BlerschVitor, FranciscoRebelo, CatarinaAdrian, Jimenez-BalsaAntunes, HelenaCarlo, GonzatoPinto, SandraSimões, SusanaKlaus, LiedlKarsten, HauptFerreira, Linoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-06T10:20:11Zoai:estudogeral.uc.pt:10316/88171Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:08:56.497177Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
title A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
spellingShingle A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
Josephine, Blersch
title_short A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
title_full A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
title_fullStr A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
title_full_unstemmed A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
title_sort A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
author Josephine, Blersch
author_facet Josephine, Blersch
Vitor, Francisco
Rebelo, Catarina
Adrian, Jimenez-Balsa
Antunes, Helena
Carlo, Gonzato
Pinto, Sandra
Simões, Susana
Klaus, Liedl
Karsten, Haupt
Ferreira, Lino
author_role author
author2 Vitor, Francisco
Rebelo, Catarina
Adrian, Jimenez-Balsa
Antunes, Helena
Carlo, Gonzato
Pinto, Sandra
Simões, Susana
Klaus, Liedl
Karsten, Haupt
Ferreira, Lino
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Josephine, Blersch
Vitor, Francisco
Rebelo, Catarina
Adrian, Jimenez-Balsa
Antunes, Helena
Carlo, Gonzato
Pinto, Sandra
Simões, Susana
Klaus, Liedl
Karsten, Haupt
Ferreira, Lino
description RNA-based therapies offer a wide range of therapeutic interventions including for the treatment of skin diseases; however, the strategies to deliver efficiently these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we synthesized a triggerable polymeric nanoparticle (NP) library composed by 160 formulations, presenting physico-chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500%) than commercial Lipofectamine in gene knockdown activity. These formulations had differential internalization by skin cells and the endosomal escape was rapid (minutes range) as shown by the recruitment of galectin-8. The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA-150-5p healed faster than wounds treated with scramble miRNA. Light-activatable NPs offer a new strategy to deliver topically non-coding RNAs.
publishDate 2019
dc.date.none.fl_str_mv 2019-11-14
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/88171
http://hdl.handle.net/10316/88171
https://doi.org/10.1002/anie.201911398
url http://hdl.handle.net/10316/88171
https://doi.org/10.1002/anie.201911398
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://onlinelibrary.wiley.com/doi/10.1002/anie.201911398
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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