Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse

Bibliographic Details
Main Author: Brito, Alexandra Manuela Fernandes
Publication Date: 2020
Other Authors: Pereira, P. M. R., Reis, R. L., Ulijn, R. V., Lewis, J. S., Pires, R. A., Pashkuleva, I.
Format: Article
Language: eng
Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Download full: https://hdl.handle.net/1822/66987
Summary: Spheroids recapitulate the organization, heterogeneity and microenvironment of solid tumors. Herein, we targeted spatiotemporally the accelerated metabolism of proliferative cells located on the spheroid surface that ensure structure maintenance and/or growth. We demonstrate that phosphorylated carbohydrate amphiphile acts as a potent antimetabolite due to glycolysis inhibition and to in situ formation of supramolecular net around spheroid surface where alkaline phosphatase is overexpressed. The efficiency of the treatment is higher in spheroids as compared to the conventional 2D cultures because of the 2-fold higher expression of glucose transporter 1 (GLUT1). Moreover, treated spheroids do not undergo following relapse.
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spelling Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse3D cancer modelsBiocatalytic self-assemblyChemotherapyGLUT1GlycolysisCiências Médicas::Biotecnologia MédicaScience & TechnologySpheroids recapitulate the organization, heterogeneity and microenvironment of solid tumors. Herein, we targeted spatiotemporally the accelerated metabolism of proliferative cells located on the spheroid surface that ensure structure maintenance and/or growth. We demonstrate that phosphorylated carbohydrate amphiphile acts as a potent antimetabolite due to glycolysis inhibition and to in situ formation of supramolecular net around spheroid surface where alkaline phosphatase is overexpressed. The efficiency of the treatment is higher in spheroids as compared to the conventional 2D cultures because of the 2-fold higher expression of glucose transporter 1 (GLUT1). Moreover, treated spheroids do not undergo following relapse.This work was supported by the EU's H2020 program (Forecast 668983), the Portuguese Foundation for Science and Technology (grants BD/113794/2015; PTDC/NANMAT/28468/2017 and PTDC/BTM-MAT/28327/2017), the US Army Research Laboratory and US Army Research Office (contract/grant W911NF-16-1-0113), NSF (grant 1808143), and the research infrastructure support of the NSF CREST Center IDEALS (grant 1547830). AB thanks to the Portuguese league against cancer for her fellowship. The authors also acknowledge the Radiochemistry and Molecular Imaging Probe Core which was supported by NIH grant P30 CA08748. This study was supported in part NIH NCI R35 CA232130 (to J.S. Lewis). P.M.R. Pereira acknowledges the Tow Foundation Postdoctoral Fellowship from the MSKCC Center for Molecular Imaging and Nanotechnology. The authors also acknowledge members of the MSKCC Radiochemistry and Molecular Imaging Probe Core and the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center of MSKCC. We also would like to acknowledge Komal Mandleywala for her help in the preparation of spheroid slides for immunocytochemistry.Royal Society of ChemistryUniversidade do MinhoBrito, Alexandra Manuela FernandesPereira, P. M. R.Reis, R. L.Ulijn, R. V.Lewis, J. S.Pires, R. A.Pashkuleva, I.2020-092020-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/66987engBrito A., Pereira P. M. R., Reis R. L., Ulijn R. V., Lewis J. S., Pires R. A., Pashkuleva I. Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse, Nanoscale, Vol. 12, doi:10.1039/D0NR05008C, 20202040-33642040-337210.1039/D0NR05008C32955076https://pubs.rsc.org/en/Content/ArticleLanding/2020/NR/D0NR05008C#!divAbstractinfo: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:RCAAP2023-07-21T11:55:20Zoai:repositorium.sdum.uminho.pt:1822/66987Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:44:52.588801Repositório 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 Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
title Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
spellingShingle Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
Brito, Alexandra Manuela Fernandes
3D cancer models
Biocatalytic self-assembly
Chemotherapy
GLUT1
Glycolysis
Ciências Médicas::Biotecnologia Médica
Science & Technology
title_short Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
title_full Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
title_fullStr Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
title_full_unstemmed Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
title_sort Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
author Brito, Alexandra Manuela Fernandes
author_facet Brito, Alexandra Manuela Fernandes
Pereira, P. M. R.
Reis, R. L.
Ulijn, R. V.
Lewis, J. S.
Pires, R. A.
Pashkuleva, I.
author_role author
author2 Pereira, P. M. R.
Reis, R. L.
Ulijn, R. V.
Lewis, J. S.
Pires, R. A.
Pashkuleva, I.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Brito, Alexandra Manuela Fernandes
Pereira, P. M. R.
Reis, R. L.
Ulijn, R. V.
Lewis, J. S.
Pires, R. A.
Pashkuleva, I.
dc.subject.por.fl_str_mv 3D cancer models
Biocatalytic self-assembly
Chemotherapy
GLUT1
Glycolysis
Ciências Médicas::Biotecnologia Médica
Science & Technology
topic 3D cancer models
Biocatalytic self-assembly
Chemotherapy
GLUT1
Glycolysis
Ciências Médicas::Biotecnologia Médica
Science & Technology
description Spheroids recapitulate the organization, heterogeneity and microenvironment of solid tumors. Herein, we targeted spatiotemporally the accelerated metabolism of proliferative cells located on the spheroid surface that ensure structure maintenance and/or growth. We demonstrate that phosphorylated carbohydrate amphiphile acts as a potent antimetabolite due to glycolysis inhibition and to in situ formation of supramolecular net around spheroid surface where alkaline phosphatase is overexpressed. The efficiency of the treatment is higher in spheroids as compared to the conventional 2D cultures because of the 2-fold higher expression of glucose transporter 1 (GLUT1). Moreover, treated spheroids do not undergo following relapse.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
2020-09-01T00:00:00Z
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 https://hdl.handle.net/1822/66987
url https://hdl.handle.net/1822/66987
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brito A., Pereira P. M. R., Reis R. L., Ulijn R. V., Lewis J. S., Pires R. A., Pashkuleva I. Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse, Nanoscale, Vol. 12, doi:10.1039/D0NR05008C, 2020
2040-3364
2040-3372
10.1039/D0NR05008C
32955076
https://pubs.rsc.org/en/Content/ArticleLanding/2020/NR/D0NR05008C#!divAbstract
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 Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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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