Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells

Detalhes bibliográficos
Autor(a) principal: Carvalho, A. M.
Data de Publicação: 2022
Outros Autores: Valcarcel, J., Costa, Diana Pereira Soares, Gomes, M., Vázquez, J. A., Reis, R. L., Novoa-Carballal, Ramon, Pashkuleva, I.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/1822/79409
Resumo: We report on the synthesis of hyaluronan (HA) brush-like copolymers and their application as antagonists of tumorigenic CD44-HA interactions. HA (4.8 kDa, ca. 24 saccharides) was grafted on 2-hydrohyethyl methacrylate (HEMA) by end-on oxime ligation. The obtained copolymers were compared with low and high molecular weight HA in terms of hydrolysis kinetics in the presence of hyaluronidase (isothermal titration calorimetry) and interactions with CD44 (surface plasmon resonance). The results evidenced that the high molecular weight HA and HA-g-HEMA have a much higher affinity to CD44 than low molecular weight HA. Additionally, slower enzymatic degradation was observed for the copolymer, making it an excellent candidate for active targeting of tumorigenic CD44-HA interactions. We, therefore, investigated the effect of the copolymer on cancer cell lines with different expression of CD44 and observed an efficient declustering of CD44 that is usually associated with reduction of metastasis and drug resistance.
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spelling Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cellsCancer therapyCD44 antagonistend-on modificationHyaluronic acidHyaluronidaseIsothermal titration calorimetryoxime ligationsurface plasmon resonanceScience & TechnologyWe report on the synthesis of hyaluronan (HA) brush-like copolymers and their application as antagonists of tumorigenic CD44-HA interactions. HA (4.8 kDa, ca. 24 saccharides) was grafted on 2-hydrohyethyl methacrylate (HEMA) by end-on oxime ligation. The obtained copolymers were compared with low and high molecular weight HA in terms of hydrolysis kinetics in the presence of hyaluronidase (isothermal titration calorimetry) and interactions with CD44 (surface plasmon resonance). The results evidenced that the high molecular weight HA and HA-g-HEMA have a much higher affinity to CD44 than low molecular weight HA. Additionally, slower enzymatic degradation was observed for the copolymer, making it an excellent candidate for active targeting of tumorigenic CD44-HA interactions. We, therefore, investigated the effect of the copolymer on cancer cell lines with different expression of CD44 and observed an efficient declustering of CD44 that is usually associated with reduction of metastasis and drug resistance.The authors thank the Portuguese Foundation for Science and Technology (FCT) for funding (Grants. SFRH/BD/114847/2016, PTDC/QUI-POL/28117/2017, and CEECIND/00814/2017). R.N.C. thanks K. Loos, A. J. Woortman, and Stephan Cairns (MALVERN) for a fruitful discussion on GPC data and R. Pacheco for discussion on ITC data.American Chemical SocietyUniversidade do MinhoCarvalho, A. M.Valcarcel, J.Costa, Diana Pereira SoaresGomes, M.Vázquez, J. A.Reis, R. L.Novoa-Carballal, RamonPashkuleva, I.2022-092022-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/79409engCarvalho A. M., Valcarcel J., Soares da Costa D., Gomes M., Vázquez J. A., Reis R. L., Novoa-Carballal R., Pashkuleva I. Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells, Acs Applied Materials & Interfaces, doi:10.1021/acsami.2c11864, 20221944-825210.1021/acsami.2c1186436053163https://doi.org/10.1021/acsami.2c11864info: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:RCAAP2023-12-02T01:20:03Zoai:repositorium.sdum.uminho.pt:1822/79409Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:29:06.011832Repositório 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 Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
title Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
spellingShingle Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
Carvalho, A. M.
Cancer therapy
CD44 antagonist
end-on modification
Hyaluronic acid
Hyaluronidase
Isothermal titration calorimetry
oxime ligation
surface plasmon resonance
Science & Technology
title_short Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
title_full Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
title_fullStr Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
title_full_unstemmed Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
title_sort Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells
author Carvalho, A. M.
author_facet Carvalho, A. M.
Valcarcel, J.
Costa, Diana Pereira Soares
Gomes, M.
Vázquez, J. A.
Reis, R. L.
Novoa-Carballal, Ramon
Pashkuleva, I.
author_role author
author2 Valcarcel, J.
Costa, Diana Pereira Soares
Gomes, M.
Vázquez, J. A.
Reis, R. L.
Novoa-Carballal, Ramon
Pashkuleva, I.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Carvalho, A. M.
Valcarcel, J.
Costa, Diana Pereira Soares
Gomes, M.
Vázquez, J. A.
Reis, R. L.
Novoa-Carballal, Ramon
Pashkuleva, I.
dc.subject.por.fl_str_mv Cancer therapy
CD44 antagonist
end-on modification
Hyaluronic acid
Hyaluronidase
Isothermal titration calorimetry
oxime ligation
surface plasmon resonance
Science & Technology
topic Cancer therapy
CD44 antagonist
end-on modification
Hyaluronic acid
Hyaluronidase
Isothermal titration calorimetry
oxime ligation
surface plasmon resonance
Science & Technology
description We report on the synthesis of hyaluronan (HA) brush-like copolymers and their application as antagonists of tumorigenic CD44-HA interactions. HA (4.8 kDa, ca. 24 saccharides) was grafted on 2-hydrohyethyl methacrylate (HEMA) by end-on oxime ligation. The obtained copolymers were compared with low and high molecular weight HA in terms of hydrolysis kinetics in the presence of hyaluronidase (isothermal titration calorimetry) and interactions with CD44 (surface plasmon resonance). The results evidenced that the high molecular weight HA and HA-g-HEMA have a much higher affinity to CD44 than low molecular weight HA. Additionally, slower enzymatic degradation was observed for the copolymer, making it an excellent candidate for active targeting of tumorigenic CD44-HA interactions. We, therefore, investigated the effect of the copolymer on cancer cell lines with different expression of CD44 and observed an efficient declustering of CD44 that is usually associated with reduction of metastasis and drug resistance.
publishDate 2022
dc.date.none.fl_str_mv 2022-09
2022-09-01T00:00:00Z
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/1822/79409
url https://hdl.handle.net/1822/79409
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Carvalho A. M., Valcarcel J., Soares da Costa D., Gomes M., Vázquez J. A., Reis R. L., Novoa-Carballal R., Pashkuleva I. Hyaluronan brush-like copolymers promote CD44 declustering in breast cancer cells, Acs Applied Materials & Interfaces, doi:10.1021/acsami.2c11864, 2022
1944-8252
10.1021/acsami.2c11864
36053163
https://doi.org/10.1021/acsami.2c11864
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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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