Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles

Detalhes bibliográficos
Autor(a) principal: Carvalho, Suzana [UNESP]
Data de Publicação: 2023
Outros Autores: Silveira, Maria José, Domingues, Mariana, Ferreira, Bárbara, Pereira, Catarina Leite, Gremião, Maria Palmira [UNESP], Sarmento, Bruno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1002/adtp.202200282
http://hdl.handle.net/11449/246703
Resumo: The encapsulation of bevacizumab (BVZ), angiogenesis inhibitor antibody, into nanocarriers is explored aiming at enhancing its efficacy in colorectal cancer (CRC) treatment while eliminating potential side effects. Still, the translation of such nanomedicines into clinics is not straightforward owing to their preclinical screening in simplistic models, that do not mimic the complexity and heterogeneity of the CRC microenvironment. Herein, the development of a multicellular spheroid of CRC as an advanced preclinical model of CRC capable of screening the antiangiogenic potential of novel nanomedicines is proposed. For that, a quadruple co-culture is established through the combination of HCT116 cells, human pulmonary microvascular endothelial cell (HPMEC), fibroblasts, and macrophages. It is demonstrated that the developed model displays intrinsic CRC features, such as the organization of cells, expression of tumor microenvironment, extracellular matrix, and the formation of a necrotic core. Moreover, the model is shown to be composed mostly of HCT116 (93%), followed by hypoxia-inducible factor (3%), HPMEC (3%), and macrophages (1%). Gellan gum/chitosan nanoparticles encapsulating BVZ exhibit superior antiangiogenic properties when compared to free BVZ. Overall, the developed nanoparticles can further be explored as a promising approach in CRC treatment.
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spelling Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticlesangiogenesisbevacizumabcolorectal cancerdrug deliverymulticellular tumor spheroidspolymeric nanoparticlestumor microenvironmentThe encapsulation of bevacizumab (BVZ), angiogenesis inhibitor antibody, into nanocarriers is explored aiming at enhancing its efficacy in colorectal cancer (CRC) treatment while eliminating potential side effects. Still, the translation of such nanomedicines into clinics is not straightforward owing to their preclinical screening in simplistic models, that do not mimic the complexity and heterogeneity of the CRC microenvironment. Herein, the development of a multicellular spheroid of CRC as an advanced preclinical model of CRC capable of screening the antiangiogenic potential of novel nanomedicines is proposed. For that, a quadruple co-culture is established through the combination of HCT116 cells, human pulmonary microvascular endothelial cell (HPMEC), fibroblasts, and macrophages. It is demonstrated that the developed model displays intrinsic CRC features, such as the organization of cells, expression of tumor microenvironment, extracellular matrix, and the formation of a necrotic core. Moreover, the model is shown to be composed mostly of HCT116 (93%), followed by hypoxia-inducible factor (3%), HPMEC (3%), and macrophages (1%). Gellan gum/chitosan nanoparticles encapsulating BVZ exhibit superior antiangiogenic properties when compared to free BVZ. Overall, the developed nanoparticles can further be explored as a promising approach in CRC treatment.School of Pharmaceutical Sciences São Paulo State University (UNESP), SPi3S – Instituto de Investigação e Inovação em Saúde University of PortoINEB – Instituto de Engenharia Biomédica University of PortoCESPU IUCSSchool of Pharmaceutical Sciences São Paulo State University (UNESP), SPUniversidade Estadual Paulista (UNESP)University of PortoIUCSCarvalho, Suzana [UNESP]Silveira, Maria JoséDomingues, MarianaFerreira, BárbaraPereira, Catarina LeiteGremião, Maria Palmira [UNESP]Sarmento, Bruno2023-07-29T12:48:11Z2023-07-29T12:48:11Z2023-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/adtp.202200282Advanced Therapeutics, v. 6, n. 4, 2023.2366-3987http://hdl.handle.net/11449/24670310.1002/adtp.2022002822-s2.0-85146728365Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAdvanced Therapeuticsinfo:eu-repo/semantics/openAccess2023-07-29T12:48:11Zoai:repositorio.unesp.br:11449/246703Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:00:44.552147Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
title Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
spellingShingle Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
Carvalho, Suzana [UNESP]
angiogenesis
bevacizumab
colorectal cancer
drug delivery
multicellular tumor spheroids
polymeric nanoparticles
tumor microenvironment
title_short Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
title_full Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
title_fullStr Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
title_full_unstemmed Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
title_sort Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles
author Carvalho, Suzana [UNESP]
author_facet Carvalho, Suzana [UNESP]
Silveira, Maria José
Domingues, Mariana
Ferreira, Bárbara
Pereira, Catarina Leite
Gremião, Maria Palmira [UNESP]
Sarmento, Bruno
author_role author
author2 Silveira, Maria José
Domingues, Mariana
Ferreira, Bárbara
Pereira, Catarina Leite
Gremião, Maria Palmira [UNESP]
Sarmento, Bruno
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
University of Porto
IUCS
dc.contributor.author.fl_str_mv Carvalho, Suzana [UNESP]
Silveira, Maria José
Domingues, Mariana
Ferreira, Bárbara
Pereira, Catarina Leite
Gremião, Maria Palmira [UNESP]
Sarmento, Bruno
dc.subject.por.fl_str_mv angiogenesis
bevacizumab
colorectal cancer
drug delivery
multicellular tumor spheroids
polymeric nanoparticles
tumor microenvironment
topic angiogenesis
bevacizumab
colorectal cancer
drug delivery
multicellular tumor spheroids
polymeric nanoparticles
tumor microenvironment
description The encapsulation of bevacizumab (BVZ), angiogenesis inhibitor antibody, into nanocarriers is explored aiming at enhancing its efficacy in colorectal cancer (CRC) treatment while eliminating potential side effects. Still, the translation of such nanomedicines into clinics is not straightforward owing to their preclinical screening in simplistic models, that do not mimic the complexity and heterogeneity of the CRC microenvironment. Herein, the development of a multicellular spheroid of CRC as an advanced preclinical model of CRC capable of screening the antiangiogenic potential of novel nanomedicines is proposed. For that, a quadruple co-culture is established through the combination of HCT116 cells, human pulmonary microvascular endothelial cell (HPMEC), fibroblasts, and macrophages. It is demonstrated that the developed model displays intrinsic CRC features, such as the organization of cells, expression of tumor microenvironment, extracellular matrix, and the formation of a necrotic core. Moreover, the model is shown to be composed mostly of HCT116 (93%), followed by hypoxia-inducible factor (3%), HPMEC (3%), and macrophages (1%). Gellan gum/chitosan nanoparticles encapsulating BVZ exhibit superior antiangiogenic properties when compared to free BVZ. Overall, the developed nanoparticles can further be explored as a promising approach in CRC treatment.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T12:48:11Z
2023-07-29T12:48:11Z
2023-04-01
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://dx.doi.org/10.1002/adtp.202200282
Advanced Therapeutics, v. 6, n. 4, 2023.
2366-3987
http://hdl.handle.net/11449/246703
10.1002/adtp.202200282
2-s2.0-85146728365
url http://dx.doi.org/10.1002/adtp.202200282
http://hdl.handle.net/11449/246703
identifier_str_mv Advanced Therapeutics, v. 6, n. 4, 2023.
2366-3987
10.1002/adtp.202200282
2-s2.0-85146728365
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Advanced Therapeutics
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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