Cell-derived nanoplatforms for cancer therapy
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | eng |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da USP |
Texto Completo: | https://www.teses.usp.br/teses/disponiveis/76/76132/tde-03092021-114705/ |
Resumo: | Nanomaterials are promising platforms for cancer therapy due to their innate passive targeting. The success of nanomaterials into the clinics depends on their blood circulation time and accumulation in the target tissue, factors related with their ability to evade the immune system. Cell-derived nanoplatforms are an emerging technology to enhance the delivery by active targeting the tumor site, without the perks of chemical conjugations. In this thesis we report the development of biomimetic novel platforms using the cell-derived technology and their in vitro interaction in cells from tumor microenvironment. To understand of the cell-derived nanoplatforms, two different nanomaterials were synthesized and further coated with extracellular vesicles and cell membrane extract from two different cell lines. First, gold nanorods (AuNRs) were coated with two macrophage derived vesicles, cell membrane extract and extracellular vesicles. Cell membrane-coated AuNRs interacted more with the metastatic cancer cells and the extracellular vesicles interacted more with the source cells. The main difference evaluated among the coatings was the presence of the tetraspanin CD47, an immunosuppressive marker for phagocytosis. Furthermore, we developed a paclitaxel-loaded polymeric nanoparticle carrier coated with metastatic breast cancer cell membrane. All cell lines showed a preferential uptake for the nanoparticles coated with the cell membrane, with stronger interaction with the source cell and the fibroblasts. Our results pointed to the role of adhesion molecules in the homotypic bind to cancer cells and the interaction with stroma cells as a heritage of the tumor progression pathways. As a consequence of the enhanced interaction of the nanocarriers with fibroblasts, the nanoparticles were significantly cytotoxic. We also explored the tunability of the plasmonic band in relation to their composition and size and evaluated basic culture parameters for extracellular vesicles isolation by means of size distribution and concentration. |
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Cell-derived nanoplatforms for cancer therapyNanoplataformas derivadas de células para o tratamento de câncerCancer therapyCell-derivedDerivado de célulasNanomaterialsNanoplataformasTratamento de câncerNanomaterials are promising platforms for cancer therapy due to their innate passive targeting. The success of nanomaterials into the clinics depends on their blood circulation time and accumulation in the target tissue, factors related with their ability to evade the immune system. Cell-derived nanoplatforms are an emerging technology to enhance the delivery by active targeting the tumor site, without the perks of chemical conjugations. In this thesis we report the development of biomimetic novel platforms using the cell-derived technology and their in vitro interaction in cells from tumor microenvironment. To understand of the cell-derived nanoplatforms, two different nanomaterials were synthesized and further coated with extracellular vesicles and cell membrane extract from two different cell lines. First, gold nanorods (AuNRs) were coated with two macrophage derived vesicles, cell membrane extract and extracellular vesicles. Cell membrane-coated AuNRs interacted more with the metastatic cancer cells and the extracellular vesicles interacted more with the source cells. The main difference evaluated among the coatings was the presence of the tetraspanin CD47, an immunosuppressive marker for phagocytosis. Furthermore, we developed a paclitaxel-loaded polymeric nanoparticle carrier coated with metastatic breast cancer cell membrane. All cell lines showed a preferential uptake for the nanoparticles coated with the cell membrane, with stronger interaction with the source cell and the fibroblasts. Our results pointed to the role of adhesion molecules in the homotypic bind to cancer cells and the interaction with stroma cells as a heritage of the tumor progression pathways. As a consequence of the enhanced interaction of the nanocarriers with fibroblasts, the nanoparticles were significantly cytotoxic. We also explored the tunability of the plasmonic band in relation to their composition and size and evaluated basic culture parameters for extracellular vesicles isolation by means of size distribution and concentration.Os nanomateriais são plataformas promissoras para a terapia do câncer devido ao seu inato acúmulo passivo em tumores. O sucesso dos mesmos na clinica depende do seu tempo dentro da circulação sanguínea e da sua acumulação no tecido alvo, fatores relacionados com a capacidade de escapar ao sistema imunológico. As nanoplataformas derivadas de células são uma tecnologia emergente para melhorar estas propriedades através do acúmulo ativo no local do tumor. Nesta tese relatamos o desenvolvimento de plataformas biomiméticas inovadoras avaliando suas interações in vitro em células modelo do microambiente tumoral. Para compreendermos melhor as nanoplataformas derivadas de células, dois nanomateriais diferentes foram sintetizados e posteriormente revestidos. Inicialmente, os nanorods de ouro (AuNRs) foram revestidos com duas vesículas derivadas de macrófagos, vesículas de membrana celular e vesículas extracelulares. Os AuNRs revestidos de membrana celular interagiram mais com a linha celular metastática de câncer e as vesículas extracelulares interagiram com a célula de origem (macrofágos). A principal diferença avaliada entre os revestimentos foi a presença da tetraspanina CD47, imunossupressor para a fagocitose. Além disso, desenvolvemos nanopartículas poliméricas com paclitaxel, revestidas com membrana celular metastática de câncer da mama. Todas as linhagens celulares mostraram uma interação preferencial para as nanopartículas revestidas com membrana celular, tendo uma interação mais pronunciada com a célula de origem e os fibroblastos. Este resultado indica o papel das moléculas de adesão nas interações homotípicas das nanopartículas às células cancerosas, além da herança da interação da célula tumoral com as células do estroma para a progressão do tumor. Como consequência, para uma maior interação com os fibroblastos, as nanopartículas foram significativamente citotóxicas. Os resultados da tese mostram como estas novas classes de nanomateriais são desenvolvidas e as suas interações com o microambiente tumoral. Além disso, estudamos mudanças na banda plasmonica dos nanorods de ouro em relação à sua composição e tamanho. Por fim, avaliamos os parâmetros de isolamento das vesículas extracelulares por distribuição de tamanho e concentração.Biblioteca Digitais de Teses e Dissertações da USPZucolotto, ValtencirLins, Paula Maria Pincela2021-03-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/76/76132/tde-03092021-114705/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2021-09-13T19:59:01Zoai:teses.usp.br:tde-03092021-114705Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212021-09-13T19:59:01Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Cell-derived nanoplatforms for cancer therapy Nanoplataformas derivadas de células para o tratamento de câncer |
title |
Cell-derived nanoplatforms for cancer therapy |
spellingShingle |
Cell-derived nanoplatforms for cancer therapy Lins, Paula Maria Pincela Cancer therapy Cell-derived Derivado de células Nanomaterials Nanoplataformas Tratamento de câncer |
title_short |
Cell-derived nanoplatforms for cancer therapy |
title_full |
Cell-derived nanoplatforms for cancer therapy |
title_fullStr |
Cell-derived nanoplatforms for cancer therapy |
title_full_unstemmed |
Cell-derived nanoplatforms for cancer therapy |
title_sort |
Cell-derived nanoplatforms for cancer therapy |
author |
Lins, Paula Maria Pincela |
author_facet |
Lins, Paula Maria Pincela |
author_role |
author |
dc.contributor.none.fl_str_mv |
Zucolotto, Valtencir |
dc.contributor.author.fl_str_mv |
Lins, Paula Maria Pincela |
dc.subject.por.fl_str_mv |
Cancer therapy Cell-derived Derivado de células Nanomaterials Nanoplataformas Tratamento de câncer |
topic |
Cancer therapy Cell-derived Derivado de células Nanomaterials Nanoplataformas Tratamento de câncer |
description |
Nanomaterials are promising platforms for cancer therapy due to their innate passive targeting. The success of nanomaterials into the clinics depends on their blood circulation time and accumulation in the target tissue, factors related with their ability to evade the immune system. Cell-derived nanoplatforms are an emerging technology to enhance the delivery by active targeting the tumor site, without the perks of chemical conjugations. In this thesis we report the development of biomimetic novel platforms using the cell-derived technology and their in vitro interaction in cells from tumor microenvironment. To understand of the cell-derived nanoplatforms, two different nanomaterials were synthesized and further coated with extracellular vesicles and cell membrane extract from two different cell lines. First, gold nanorods (AuNRs) were coated with two macrophage derived vesicles, cell membrane extract and extracellular vesicles. Cell membrane-coated AuNRs interacted more with the metastatic cancer cells and the extracellular vesicles interacted more with the source cells. The main difference evaluated among the coatings was the presence of the tetraspanin CD47, an immunosuppressive marker for phagocytosis. Furthermore, we developed a paclitaxel-loaded polymeric nanoparticle carrier coated with metastatic breast cancer cell membrane. All cell lines showed a preferential uptake for the nanoparticles coated with the cell membrane, with stronger interaction with the source cell and the fibroblasts. Our results pointed to the role of adhesion molecules in the homotypic bind to cancer cells and the interaction with stroma cells as a heritage of the tumor progression pathways. As a consequence of the enhanced interaction of the nanocarriers with fibroblasts, the nanoparticles were significantly cytotoxic. We also explored the tunability of the plasmonic band in relation to their composition and size and evaluated basic culture parameters for extracellular vesicles isolation by means of size distribution and concentration. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-03-26 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.teses.usp.br/teses/disponiveis/76/76132/tde-03092021-114705/ |
url |
https://www.teses.usp.br/teses/disponiveis/76/76132/tde-03092021-114705/ |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
|
dc.rights.driver.fl_str_mv |
Liberar o conteúdo para acesso público. info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Liberar o conteúdo para acesso público. |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.coverage.none.fl_str_mv |
|
dc.publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da USP instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Biblioteca Digital de Teses e Dissertações da USP |
collection |
Biblioteca Digital de Teses e Dissertações da USP |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br |
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1809090347716837376 |