Exosome-based delivery of RNAi leads to breast cancer inhibition

Detalhes bibliográficos
Autor(a) principal: Silva, Renata
Data de Publicação: 2022
Outros Autores: Ferreira, Débora, Rodrigues, L. R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/1822/80447
Resumo: Breast cancer is currently the most prevalent cancer in the world. It has been reported that hyperactivation and dysregulation of key pathways, such as PI3K/AKT/mTOR (PAM), contributes to the cell's tumorigenesis and resistance to existent therapies. Herein, we sought to uncover the potential of PAM downregulation in a panel of different breast cancer cell lines with different phenotypes, through PIK3CA silencing. This oncogene was targeted with a pre-designed small interfering RNA (siRNA) transfected onto PIK3CA wild-type MDA-MB-231cells and PIK3CA mutated MDA-MB-453cells. The results suggest that the siRNA efficiently targeted PIK3CA, triggering an efficient gene silencing and a decrease on cellular viability, as well as migration capacity. Moreover, exosome-like nanovesicles were successfully isolated, characterized and incorporated into the cells and served as excellent siRNA nanocarriers, promoting an incremented and faster onset. Altogether, the data gathered shows that the combination of the validated siRNA with these nanocarriers could be a promising targeted drug delivery system for an alternative breast cancer therapy.
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spelling Exosome-based delivery of RNAi leads to breast cancer inhibitionBreast cancerDrug delivery systemExosomesScience & TechnologyBreast cancer is currently the most prevalent cancer in the world. It has been reported that hyperactivation and dysregulation of key pathways, such as PI3K/AKT/mTOR (PAM), contributes to the cell's tumorigenesis and resistance to existent therapies. Herein, we sought to uncover the potential of PAM downregulation in a panel of different breast cancer cell lines with different phenotypes, through PIK3CA silencing. This oncogene was targeted with a pre-designed small interfering RNA (siRNA) transfected onto PIK3CA wild-type MDA-MB-231cells and PIK3CA mutated MDA-MB-453cells. The results suggest that the siRNA efficiently targeted PIK3CA, triggering an efficient gene silencing and a decrease on cellular viability, as well as migration capacity. Moreover, exosome-like nanovesicles were successfully isolated, characterized and incorporated into the cells and served as excellent siRNA nanocarriers, promoting an incremented and faster onset. Altogether, the data gathered shows that the combination of the validated siRNA with these nanocarriers could be a promising targeted drug delivery system for an alternative breast cancer therapy.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit. Débora Ferreira is recipient of a fellowship supported by a doctoral advanced training (call NORTE-69-2015-15) funded by the European Social Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Débora Ferreira also acknowledges “Liga Portuguesa contra o cancro - Núcleo Regional do Norte (LPCC-530 NRN)“ for her fellowship. The authors thank Diana Vilas Boas (CEB/University of Minho) for confocal microscopy technical support.info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoSilva, RenataFerreira, DéboraRodrigues, L. R.2022-10-312022-10-31T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/80447engSilva, Renata; Ferreira, Débora; Rodrigues, Lígia R., Exosome-based delivery of RNAi leads to breast cancer inhibition. Journal of Drug Delivery Science and Technology, No. 103931, 20221773-22472588-894310.1016/j.jddst.2022.103931103931https://www.sciencedirect.com/science/article/pii/S1773224722008425info: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:RCAAP2023-07-21T12:54:19Zoai:repositorium.sdum.uminho.pt:1822/80447Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:53:49.628778Repositório 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 Exosome-based delivery of RNAi leads to breast cancer inhibition
title Exosome-based delivery of RNAi leads to breast cancer inhibition
spellingShingle Exosome-based delivery of RNAi leads to breast cancer inhibition
Silva, Renata
Breast cancer
Drug delivery system
Exosomes
Science & Technology
title_short Exosome-based delivery of RNAi leads to breast cancer inhibition
title_full Exosome-based delivery of RNAi leads to breast cancer inhibition
title_fullStr Exosome-based delivery of RNAi leads to breast cancer inhibition
title_full_unstemmed Exosome-based delivery of RNAi leads to breast cancer inhibition
title_sort Exosome-based delivery of RNAi leads to breast cancer inhibition
author Silva, Renata
author_facet Silva, Renata
Ferreira, Débora
Rodrigues, L. R.
author_role author
author2 Ferreira, Débora
Rodrigues, L. R.
author2_role author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Silva, Renata
Ferreira, Débora
Rodrigues, L. R.
dc.subject.por.fl_str_mv Breast cancer
Drug delivery system
Exosomes
Science & Technology
topic Breast cancer
Drug delivery system
Exosomes
Science & Technology
description Breast cancer is currently the most prevalent cancer in the world. It has been reported that hyperactivation and dysregulation of key pathways, such as PI3K/AKT/mTOR (PAM), contributes to the cell's tumorigenesis and resistance to existent therapies. Herein, we sought to uncover the potential of PAM downregulation in a panel of different breast cancer cell lines with different phenotypes, through PIK3CA silencing. This oncogene was targeted with a pre-designed small interfering RNA (siRNA) transfected onto PIK3CA wild-type MDA-MB-231cells and PIK3CA mutated MDA-MB-453cells. The results suggest that the siRNA efficiently targeted PIK3CA, triggering an efficient gene silencing and a decrease on cellular viability, as well as migration capacity. Moreover, exosome-like nanovesicles were successfully isolated, characterized and incorporated into the cells and served as excellent siRNA nanocarriers, promoting an incremented and faster onset. Altogether, the data gathered shows that the combination of the validated siRNA with these nanocarriers could be a promising targeted drug delivery system for an alternative breast cancer therapy.
publishDate 2022
dc.date.none.fl_str_mv 2022-10-31
2022-10-31T00:00:00Z
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 https://hdl.handle.net/1822/80447
url https://hdl.handle.net/1822/80447
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Silva, Renata; Ferreira, Débora; Rodrigues, Lígia R., Exosome-based delivery of RNAi leads to breast cancer inhibition. Journal of Drug Delivery Science and Technology, No. 103931, 2022
1773-2247
2588-8943
10.1016/j.jddst.2022.103931
103931
https://www.sciencedirect.com/science/article/pii/S1773224722008425
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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