Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
Autor(a) principal: | |
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Data de Publicação: | 2012 |
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/10316/21117 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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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) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
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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1799133752133156864 |