Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment

Detalhes bibliográficos
Autor(a) principal: Gomes-da-Silva, Lígia C.
Data de Publicação: 2012
Outros Autores: Santos, Adriana O., Bimbo, Luís M., Moura, Vera, Ramalho, José S., Lima, Maria C. Pedroso de, Simões, Sérgio, Moreira, João N.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/21117
https://doi.org/10.1016/j.ijpharm.2012.05.018
Resumo: The present work aimed at designing a lipid-based nanocarrier for siRNA delivery towards two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non27 cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co32 localization studies between the siRNA and lysosomes. Overall, the present work represents an important contribution towards a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level.
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spelling Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironmentDual-targeted deliveryLigand-mediated targetingSNALPsiRNABreast cancerThe present work aimed at designing a lipid-based nanocarrier for siRNA delivery towards two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non27 cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co32 localization studies between the siRNA and lysosomes. Overall, the present work represents an important contribution towards a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level.Elsevier2012-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/21117http://hdl.handle.net/10316/21117https://doi.org/10.1016/j.ijpharm.2012.05.018eng0378-5173http://www.sciencedirect.com/science/article/pii/S0378517312005029Gomes-da-Silva, Lígia C.Santos, Adriana O.Bimbo, Luís M.Moura, VeraRamalho, José S.Lima, Maria C. Pedroso deSimões, SérgioMoreira, João N.info: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:RCAAP2021-09-17T11:05:02Zoai:estudogeral.uc.pt:10316/21117Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:28.513390Repositório 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 Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
title Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
spellingShingle Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
Gomes-da-Silva, Lígia C.
Dual-targeted delivery
Ligand-mediated targeting
SNALP
siRNA
Breast cancer
title_short Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
title_full Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
title_fullStr Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
title_full_unstemmed Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
title_sort Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
author Gomes-da-Silva, Lígia C.
author_facet Gomes-da-Silva, Lígia C.
Santos, Adriana O.
Bimbo, Luís M.
Moura, Vera
Ramalho, José S.
Lima, Maria C. Pedroso de
Simões, Sérgio
Moreira, João N.
author_role author
author2 Santos, Adriana O.
Bimbo, Luís M.
Moura, Vera
Ramalho, José S.
Lima, Maria C. Pedroso de
Simões, Sérgio
Moreira, João N.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Gomes-da-Silva, Lígia C.
Santos, Adriana O.
Bimbo, Luís M.
Moura, Vera
Ramalho, José S.
Lima, Maria C. Pedroso de
Simões, Sérgio
Moreira, João N.
dc.subject.por.fl_str_mv Dual-targeted delivery
Ligand-mediated targeting
SNALP
siRNA
Breast cancer
topic Dual-targeted delivery
Ligand-mediated targeting
SNALP
siRNA
Breast cancer
description The present work aimed at designing a lipid-based nanocarrier for siRNA delivery towards two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non27 cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co32 localization studies between the siRNA and lysosomes. Overall, the present work represents an important contribution towards a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level.
publishDate 2012
dc.date.none.fl_str_mv 2012-09
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/10316/21117
http://hdl.handle.net/10316/21117
https://doi.org/10.1016/j.ijpharm.2012.05.018
url http://hdl.handle.net/10316/21117
https://doi.org/10.1016/j.ijpharm.2012.05.018
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0378-5173
http://www.sciencedirect.com/science/article/pii/S0378517312005029
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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)
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