Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/88570 |
Resumo: | Background: T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efcacy and relatively weak side efects. Systems that optimize the stimulation of T cells to improve therapeutic efcacy are therefore in constant demand. A way to achieve this is through artifcial antigen presenting cells that are complexes between vehicles and key molecules that target relevant T cell subpopulations, eliciting antigenspecifc T cell priming. In such T cell activator systems, the vehicles chosen to deliver and present the key molecules to the targeted cell populations are of extreme importance. In this work, a new platform for the creation of T cell activator systems based on highly tailorable nanoparticles made from the natural polymer gellan gum (GG) was developed and validated. Methods: GG nanoparticles were produced by a water in oil emulsion procedure, and characterized by dynamic light scattering, high resolution scanning electronic microscopy and water uptake. Their biocompatibility with cultured cells was assessed by a metabolic activity assay. Surface functionalization was performed with anti-CD3/ CD28 antibodies via EDC/NHS or NeutrAvidin/Biotin linkage. Functionalized particles were tested for their capacity to stimulate CD4+ T cells and trigger T cell cytotoxic responses. Results: Nanoparticles were approximately 150 nm in size, with a stable structure and no detectable cytotoxicity. Water uptake originated a weight gain of up to 3200%. The functional antibodies did efciently bind to the nanoparticles, as confrmed by SDS-PAGE, which then targeted the desired CD4+ populations, as confrmed by confocal microscopy. The developed system presented a more sustained T cell activation over time when compared to commercial alternatives. Concurrently, the expression of higher levels of key cytotoxic pathway molecules granzyme B/perforin was induced, suggesting a greater cytotoxic potential for future application in adoptive cancer therapy. Conclusions: Our results show that GG nanoparticles were successfully used as a highly tailorable T cell activator system platform capable of T cell expansion and re-education. |
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Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systemsCytotoxic T cellsGellan GumNanoparticlesT cell stimulationScience & TechnologyBackground: T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efcacy and relatively weak side efects. Systems that optimize the stimulation of T cells to improve therapeutic efcacy are therefore in constant demand. A way to achieve this is through artifcial antigen presenting cells that are complexes between vehicles and key molecules that target relevant T cell subpopulations, eliciting antigenspecifc T cell priming. In such T cell activator systems, the vehicles chosen to deliver and present the key molecules to the targeted cell populations are of extreme importance. In this work, a new platform for the creation of T cell activator systems based on highly tailorable nanoparticles made from the natural polymer gellan gum (GG) was developed and validated. Methods: GG nanoparticles were produced by a water in oil emulsion procedure, and characterized by dynamic light scattering, high resolution scanning electronic microscopy and water uptake. Their biocompatibility with cultured cells was assessed by a metabolic activity assay. Surface functionalization was performed with anti-CD3/ CD28 antibodies via EDC/NHS or NeutrAvidin/Biotin linkage. Functionalized particles were tested for their capacity to stimulate CD4+ T cells and trigger T cell cytotoxic responses. Results: Nanoparticles were approximately 150 nm in size, with a stable structure and no detectable cytotoxicity. Water uptake originated a weight gain of up to 3200%. The functional antibodies did efciently bind to the nanoparticles, as confrmed by SDS-PAGE, which then targeted the desired CD4+ populations, as confrmed by confocal microscopy. The developed system presented a more sustained T cell activation over time when compared to commercial alternatives. Concurrently, the expression of higher levels of key cytotoxic pathway molecules granzyme B/perforin was induced, suggesting a greater cytotoxic potential for future application in adoptive cancer therapy. Conclusions: Our results show that GG nanoparticles were successfully used as a highly tailorable T cell activator system platform capable of T cell expansion and re-education.Authors would like to acknowledge the fnancial support from the European Research Council through the Starting Grant “CapBed” (ERC-2018-STG-805411), FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior) through the grants SFRH/BD/119756/2016 (D.B.R.) and IF/00347/2015 (R.P.P.) and to the FSE/POCH (Fundo Social Europeu através do Programa Operacional do Capital Humano) under the scope of the PD/169/2013, NORTE-08–5369-FSE-000037 (H.R.M.).BioMed Central (BMC)Universidade do MinhoRodrigues, Daniel BarreiraMoreira, Helena R.Cerqueira, Mariana T.Marques, A. P.Castro, António G.Reis, R. L.Pirraco, Rogério P.2022-092022-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/88570engRodrigues D. B., Moreira H. R., Cerqueira M. T., Marques A. P., Castro A. G., Reis R. L., Pirraco R. P. Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems, Biomaterials Research, Vol. 26, pp. 48, doi:10.1186/s40824-022-00297-z, 20221226-46012055-712410.1186/s40824-022-00297-z48https://dx.doi.org/10.1186/s40824-022-00297-zinfo: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:RCAAP2024-02-10T01:21:00Zoai:repositorium.sdum.uminho.pt:1822/88570Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:37:17.525262Repositório 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 |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
title |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
spellingShingle |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems Rodrigues, Daniel Barreira Cytotoxic T cells Gellan Gum Nanoparticles T cell stimulation Science & Technology |
title_short |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
title_full |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
title_fullStr |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
title_full_unstemmed |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
title_sort |
Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
author |
Rodrigues, Daniel Barreira |
author_facet |
Rodrigues, Daniel Barreira Moreira, Helena R. Cerqueira, Mariana T. Marques, A. P. Castro, António G. Reis, R. L. Pirraco, Rogério P. |
author_role |
author |
author2 |
Moreira, Helena R. Cerqueira, Mariana T. Marques, A. P. Castro, António G. Reis, R. L. Pirraco, Rogério P. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Rodrigues, Daniel Barreira Moreira, Helena R. Cerqueira, Mariana T. Marques, A. P. Castro, António G. Reis, R. L. Pirraco, Rogério P. |
dc.subject.por.fl_str_mv |
Cytotoxic T cells Gellan Gum Nanoparticles T cell stimulation Science & Technology |
topic |
Cytotoxic T cells Gellan Gum Nanoparticles T cell stimulation Science & Technology |
description |
Background: T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efcacy and relatively weak side efects. Systems that optimize the stimulation of T cells to improve therapeutic efcacy are therefore in constant demand. A way to achieve this is through artifcial antigen presenting cells that are complexes between vehicles and key molecules that target relevant T cell subpopulations, eliciting antigenspecifc T cell priming. In such T cell activator systems, the vehicles chosen to deliver and present the key molecules to the targeted cell populations are of extreme importance. In this work, a new platform for the creation of T cell activator systems based on highly tailorable nanoparticles made from the natural polymer gellan gum (GG) was developed and validated. Methods: GG nanoparticles were produced by a water in oil emulsion procedure, and characterized by dynamic light scattering, high resolution scanning electronic microscopy and water uptake. Their biocompatibility with cultured cells was assessed by a metabolic activity assay. Surface functionalization was performed with anti-CD3/ CD28 antibodies via EDC/NHS or NeutrAvidin/Biotin linkage. Functionalized particles were tested for their capacity to stimulate CD4+ T cells and trigger T cell cytotoxic responses. Results: Nanoparticles were approximately 150 nm in size, with a stable structure and no detectable cytotoxicity. Water uptake originated a weight gain of up to 3200%. The functional antibodies did efciently bind to the nanoparticles, as confrmed by SDS-PAGE, which then targeted the desired CD4+ populations, as confrmed by confocal microscopy. The developed system presented a more sustained T cell activation over time when compared to commercial alternatives. Concurrently, the expression of higher levels of key cytotoxic pathway molecules granzyme B/perforin was induced, suggesting a greater cytotoxic potential for future application in adoptive cancer therapy. Conclusions: Our results show that GG nanoparticles were successfully used as a highly tailorable T cell activator system platform capable of T cell expansion and re-education. |
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/1822/88570 |
url |
https://hdl.handle.net/1822/88570 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Rodrigues D. B., Moreira H. R., Cerqueira M. T., Marques A. P., Castro A. G., Reis R. L., Pirraco R. P. Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems, Biomaterials Research, Vol. 26, pp. 48, doi:10.1186/s40824-022-00297-z, 2022 1226-4601 2055-7124 10.1186/s40824-022-00297-z 48 https://dx.doi.org/10.1186/s40824-022-00297-z |
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 |
BioMed Central (BMC) |
publisher.none.fl_str_mv |
BioMed Central (BMC) |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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