Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.13/2649 |
Resumo: | Nanogels (NGs) are three dimensional networks composed of hydrophilic or amphiphilic polymer chains, allowing for effective and homogeneous encapsulation of drugs, genes or imaging contrast agents for biomedical applications. Polyethylenimine (PEI), possessing sufficient positively charged amine groups, is an ideal platform for NG development. In this study, we synthesized PEI-based NGs loaded with both MR contrast agent ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and the anticancer drug doxorubicin (DOX) for tumor theranostics. The synthesis of PEI-based NGs was first carried out by an inverse mini-emulsion (water-in-oil, W/O) crosslinking strategy. Secondly, the NGs were conjugated with ultrasmall Fe3O4 NPs which was performed via a hydrothermal method through 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. Then the amine groups of the NGs were acetylated by acetic anhydride. The formed PEI-based NGs possess good dispersibility and cytocompatibility. The drug release profile was studied, as well as the impact of the environmental pH on the release rate of DOX. Results proved that the hybrid NGs facilitated a sustained release of DOX with a higher release rate under acidic pH. Furthermore, in vitro studies showed that Fe3O4/PEI-Ac NGs had no cytotoxicity towards 4T1 tumor cells, unlike Fe3O4/PEI-Ac NGs/DOX complexes and Free DOX. The PEI-based NGs presented significantly enhanced r1 relaxivity of 2.29 mM-1s-1 when compared to free ultrasmall Fe3O4 NPs (1.15 mM-1s-1), as well as excellent drug loading efficiency (51.4%). Strikingly, the NGs presented enhanced T1 MR imaging ability and a high therapeutic efficacy towards cancer cells in vitro and a xenografted tumor model in vivo. |
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Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapyPolytheylenimineNanogelsUltrasmall ironoxide NPsDoxorubicinTheranosticsPolietileniminaNanogelNanopartículas de óxido de ferroDoxorubicinaTeranósticaNanochemistry and Nanomaterials.Faculdade de Ciências Exatas e da EngenhariaDomínio/Área Científica::Engenharia e Tecnologia::NanotecnologiaNanogels (NGs) are three dimensional networks composed of hydrophilic or amphiphilic polymer chains, allowing for effective and homogeneous encapsulation of drugs, genes or imaging contrast agents for biomedical applications. Polyethylenimine (PEI), possessing sufficient positively charged amine groups, is an ideal platform for NG development. In this study, we synthesized PEI-based NGs loaded with both MR contrast agent ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and the anticancer drug doxorubicin (DOX) for tumor theranostics. The synthesis of PEI-based NGs was first carried out by an inverse mini-emulsion (water-in-oil, W/O) crosslinking strategy. Secondly, the NGs were conjugated with ultrasmall Fe3O4 NPs which was performed via a hydrothermal method through 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. Then the amine groups of the NGs were acetylated by acetic anhydride. The formed PEI-based NGs possess good dispersibility and cytocompatibility. The drug release profile was studied, as well as the impact of the environmental pH on the release rate of DOX. Results proved that the hybrid NGs facilitated a sustained release of DOX with a higher release rate under acidic pH. Furthermore, in vitro studies showed that Fe3O4/PEI-Ac NGs had no cytotoxicity towards 4T1 tumor cells, unlike Fe3O4/PEI-Ac NGs/DOX complexes and Free DOX. The PEI-based NGs presented significantly enhanced r1 relaxivity of 2.29 mM-1s-1 when compared to free ultrasmall Fe3O4 NPs (1.15 mM-1s-1), as well as excellent drug loading efficiency (51.4%). Strikingly, the NGs presented enhanced T1 MR imaging ability and a high therapeutic efficacy towards cancer cells in vitro and a xenografted tumor model in vivo.Os nanogéis (NGs) são redes tridimensionais compostas por cadeias poliméricas, hidrofílicas ou anfifílicas, que permitem o encapsulamento efetivo e homogéneo de fármacos, genes ou agentes de contraste para aplicações biomédicas. A polietilenimina (PEI), por possuir muitos grupos amina carregados positivamente, constitui uma plataforma ideal para o desenvolvimento de NGs. Neste estudo, sintetizaram-se NGs à base de PEI, nos quais se incorporaram nanopartículas de óxido de ferro (Fe3O4) e também o fármaco anticancerígeno doxorubicina (DOX) com vista ao tratamento e simultâneo diagnóstico de tumores. Em primeiro lugar, a preparação dos NGs foi levada a cabo através de um processo de reticulação de mini-emulsão inversa (água em óleo). De seguida, os NGs foram conjugados com nanopartículas de Fe3O4 usando um método hidrotérmico e a estratégia de síntese química com base na 1-etil-3-(3-dimetilaminopropil)carbodiimida (EDC). Seguidamente, os grupos amina foram acetilados usando anidrido acético, obtendo-se os produtos finais (Fe3O4/PEI-Ac NGs). Os NGs assim formados mostraram possuir uma boa dispersibilidade e citocompatibilidade. A velocidade de libertação da DOX a partir dos NGs foi estudada, assim como o impacto do pH nesse processo. Os resultados mostraram haver uma libertação sustentada do fármaco que atinge velocidades superiores a valores ácidos de pH. Adicionalmente, estudos realizados in vitro com a linha celular tumoral 4T1 mostraram que os Fe3O4/PEI-Ac NGs não são citotóxicos, ao contrário do que acontece com os complexos Fe3O4/PEI-Ac NGs/DOX e a DOX livre. Os NGs preparados apresentam uma relaxividade r1 significativamente aumentada (2.29 mM-1s-1) comparativamente com as nanopartículas de Fe3O4 livres (1.15 mM-1s-1), bem como uma excelente eficiência de encapsulamento de DOX (51.4%). Surpreendentemente, os nanogéis apresentam uma capacidade aumentada para imagiologia de ressonância magnética T1 e uma elevada eficácia terapêutica, quer in vitro usando células tumorais, quer num modelo de tumor (xenoenxerto) in vivo.Shi, XiangyangTómás, Helena Maria Pires GasparDigitUMaZou, Yu2021-03-16T01:30:13Z2019-09-262019-09-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.13/2649TID:202339742enginfo: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:RCAAP2023-03-26T03:38:04Zoai:digituma.uma.pt:10400.13/2649Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:05:25.998634Repositório 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 |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
title |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
spellingShingle |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy Zou, Yu Polytheylenimine Nanogels Ultrasmall ironoxide NPs Doxorubicin Theranostics Polietilenimina Nanogel Nanopartículas de óxido de ferro Doxorubicina Teranóstica Nanochemistry and Nanomaterials . Faculdade de Ciências Exatas e da Engenharia Domínio/Área Científica::Engenharia e Tecnologia::Nanotecnologia |
title_short |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
title_full |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
title_fullStr |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
title_full_unstemmed |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
title_sort |
Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy |
author |
Zou, Yu |
author_facet |
Zou, Yu |
author_role |
author |
dc.contributor.none.fl_str_mv |
Shi, Xiangyang Tómás, Helena Maria Pires Gaspar DigitUMa |
dc.contributor.author.fl_str_mv |
Zou, Yu |
dc.subject.por.fl_str_mv |
Polytheylenimine Nanogels Ultrasmall ironoxide NPs Doxorubicin Theranostics Polietilenimina Nanogel Nanopartículas de óxido de ferro Doxorubicina Teranóstica Nanochemistry and Nanomaterials . Faculdade de Ciências Exatas e da Engenharia Domínio/Área Científica::Engenharia e Tecnologia::Nanotecnologia |
topic |
Polytheylenimine Nanogels Ultrasmall ironoxide NPs Doxorubicin Theranostics Polietilenimina Nanogel Nanopartículas de óxido de ferro Doxorubicina Teranóstica Nanochemistry and Nanomaterials . Faculdade de Ciências Exatas e da Engenharia Domínio/Área Científica::Engenharia e Tecnologia::Nanotecnologia |
description |
Nanogels (NGs) are three dimensional networks composed of hydrophilic or amphiphilic polymer chains, allowing for effective and homogeneous encapsulation of drugs, genes or imaging contrast agents for biomedical applications. Polyethylenimine (PEI), possessing sufficient positively charged amine groups, is an ideal platform for NG development. In this study, we synthesized PEI-based NGs loaded with both MR contrast agent ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and the anticancer drug doxorubicin (DOX) for tumor theranostics. The synthesis of PEI-based NGs was first carried out by an inverse mini-emulsion (water-in-oil, W/O) crosslinking strategy. Secondly, the NGs were conjugated with ultrasmall Fe3O4 NPs which was performed via a hydrothermal method through 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. Then the amine groups of the NGs were acetylated by acetic anhydride. The formed PEI-based NGs possess good dispersibility and cytocompatibility. The drug release profile was studied, as well as the impact of the environmental pH on the release rate of DOX. Results proved that the hybrid NGs facilitated a sustained release of DOX with a higher release rate under acidic pH. Furthermore, in vitro studies showed that Fe3O4/PEI-Ac NGs had no cytotoxicity towards 4T1 tumor cells, unlike Fe3O4/PEI-Ac NGs/DOX complexes and Free DOX. The PEI-based NGs presented significantly enhanced r1 relaxivity of 2.29 mM-1s-1 when compared to free ultrasmall Fe3O4 NPs (1.15 mM-1s-1), as well as excellent drug loading efficiency (51.4%). Strikingly, the NGs presented enhanced T1 MR imaging ability and a high therapeutic efficacy towards cancer cells in vitro and a xenografted tumor model in vivo. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-09-26 2019-09-26T00:00:00Z 2021-03-16T01:30:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.13/2649 TID:202339742 |
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http://hdl.handle.net/10400.13/2649 |
identifier_str_mv |
TID:202339742 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799129925210341376 |