Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/1822/56296 |
Resumo: | Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational changes from random coil to β-sheet conformation under physiological conditions. A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF hydrogels converted into β-sheet structure induced the formation of TUNEL-positive apoptotic cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment on the programed tumor cells death, by using rapidly responsive SF hydrogels as 3D in vitro tumor models. |
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Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death3D in vitro modelsApoptosisEnzymatically crosslinked hydrogelsSilk FibroinScience & TechnologyTimely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational changes from random coil to β-sheet conformation under physiological conditions. A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF hydrogels converted into β-sheet structure induced the formation of TUNEL-positive apoptotic cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment on the programed tumor cells death, by using rapidly responsive SF hydrogels as 3D in vitro tumor models.This study was funded by the Portuguese Foundation for Science and Technology (FCT; http://www.fct.pt) project PEst (PEst-C/SAU/LA0026/2013) under POFC and/or FEDER programs, attributed to RLR; Grants under the Investigator FCT program: IF/00423/2012 and IF/01285/2015 (JMO), IF/00411/2013 (ALO) and IF/00115/2015 (JSC); Postdoctoral fellows: SFRH/BPD/94277/2013 (CG), SFRH/BPD/108763/2015 (SP), SFRH/BPD/100957/2014 (HR); PhD scholarship PD/BD/113806/2015 attributed to VPR under the financial support from FCT/MCTES and FSE/POCH, PD/59/2013. An internal R&D grant of Anasys Instruments Corp provided support in the form of salary for author AR, but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the author contributions section. The remaining co-authors did not receive any funding from Anasys Instruments Corp.info:eu-repo/semantics/publishedVersionPLOSUniversidade do MinhoRibeiro, V. P.Silva-Correia, J.Gonçalves, C.Pina, S.Radhouani, HajerMontonen, ToniHyttinen, J.Roy, A.Oliveira, A. L.Reis, R. L.Oliveira, J. M.2018-042018-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/56296engRibeiro V. P., Silva-Correia J., Gonçalves C., Pina S., Radhouani H., Hyttinen J., Roy A., Oliveira A. L., Reis R. L., Oliveira J. M. Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death, PLoS ONE, Vol. 13, Issue 4, pp. e0194441, doi:10.1371/journal.pone.0194441, 20181932-620310.1371/journal.pone.019444129617395http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194441info: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:RCAAP2023-07-21T12:23:12ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
title |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
spellingShingle |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death Ribeiro, V. P. 3D in vitro models Apoptosis Enzymatically crosslinked hydrogels Silk Fibroin Science & Technology |
title_short |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
title_full |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
title_fullStr |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
title_full_unstemmed |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
title_sort |
Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death |
author |
Ribeiro, V. P. |
author_facet |
Ribeiro, V. P. Silva-Correia, J. Gonçalves, C. Pina, S. Radhouani, Hajer Montonen, Toni Hyttinen, J. Roy, A. Oliveira, A. L. Reis, R. L. Oliveira, J. M. |
author_role |
author |
author2 |
Silva-Correia, J. Gonçalves, C. Pina, S. Radhouani, Hajer Montonen, Toni Hyttinen, J. Roy, A. Oliveira, A. L. Reis, R. L. Oliveira, J. M. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Ribeiro, V. P. Silva-Correia, J. Gonçalves, C. Pina, S. Radhouani, Hajer Montonen, Toni Hyttinen, J. Roy, A. Oliveira, A. L. Reis, R. L. Oliveira, J. M. |
dc.subject.por.fl_str_mv |
3D in vitro models Apoptosis Enzymatically crosslinked hydrogels Silk Fibroin Science & Technology |
topic |
3D in vitro models Apoptosis Enzymatically crosslinked hydrogels Silk Fibroin Science & Technology |
description |
Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational changes from random coil to β-sheet conformation under physiological conditions. A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF hydrogels converted into β-sheet structure induced the formation of TUNEL-positive apoptotic cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment on the programed tumor cells death, by using rapidly responsive SF hydrogels as 3D in vitro tumor models. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-04 2018-04-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/56296 |
url |
http://hdl.handle.net/1822/56296 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ribeiro V. P., Silva-Correia J., Gonçalves C., Pina S., Radhouani H., Hyttinen J., Roy A., Oliveira A. L., Reis R. L., Oliveira J. M. Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death, PLoS ONE, Vol. 13, Issue 4, pp. e0194441, doi:10.1371/journal.pone.0194441, 2018 1932-6203 10.1371/journal.pone.0194441 29617395 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194441 |
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 |
PLOS |
publisher.none.fl_str_mv |
PLOS |
dc.source.none.fl_str_mv |
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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 |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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