A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133982523129856 |