Development of multifunctional phototherapeutic nanoagents
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.6/10549 |
Resumo: | Breast cancer remains as one of the world's deadliest diseases, a fact that can be explained by the low efficacy and systemic toxicity of the therapies currently in use in the clinic. Recently, researchers have been developing new therapeutic approaches, among which the chemo-photothermal therapy mediated by nanomaterials has been showing promising results, due to its capacity to produce a spatio-temporal controlled anti-cancer effect. During the development of nanomaterials aimed for cancer chemo-photothermal therapy, their efficacy is initially assessed using monolayers of cancer cells (2D in vitro models). The best formulations screened in 2D are then evaluated in tumor bearing mice (in vivo models). However, the 2D in vitro models present some drawbacks, since they are unable to mimic the key features of the in vivo solid tumors. Due to this reason, several nanoformulations that displayed therapeutic efficacy when tested in the 2D in vitro models induce a subpar effect in vivo. To overcome this limitation, spheroids (3D in vitro models) have recently emerged for the screening of nanomedicines. In fact, spheroids are able to reproduce the main properties of the in vivo solid tumors, namely: i) their 3D architecture, ii) microenvironment (gradients of nutrients, pH and gases), iii) cellular and acellular composition, and iv) biochemical and physical resistance patterns to the therapeutics. In this Master thesis, the efficacy of the chemo-photothermal therapy mediated by nanoparticles based on bovine serum albumin functionalized with sulfobetaine methacrylate, co-encapsulating IR780 and Doxorubicin (IR+DOX/SBMA-BSA NPs) was evaluated in 2D in vitro models and spheroids. In 2D in vitro models, it was found that photothermal therapy mediated by nanoparticles loading IR780 (IR/SBMA-BSA NPs and NIR irradiation) reduced cells’ viability to about 58 %, while chemotherapy induced by nanomaterials (IR+DOX/SBMA-BSA NPs) led to a decrease in their viability to 29 %. In addition, the nanoparticles’ mediated chemo-photothermal therapy (IR+DOX/SBMA-BSA NPs and NIR irradiation) achieved a better therapeutic effect by reducing cells’ viability to 1 %. On the other hand, when the therapies were screened on 3D breast cancer models (spheroids), the photothermal therapy mediated by the nanoparticles (IR/SBMA-BSA NPs and NIR irradiation) did not induce an appreciable cytotoxic effect, while the chemotherapy mediated by the nanostructures (IR+DOX/SBMA-BSA NPs) decreased the viability of the spheroids to 42 %. In turn, the chemo-photothermal therapy mediated by the nanomaterials (IR+DOX/SBMA-BSA NPs and NIR irradiation) was able to further reduce the viability of spheroids to 16 %, revealing that this is the most promising therapeutic modality. |
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Development of multifunctional phototherapeutic nanoagentsCancroEsferóidesNanopartículasQuimioterapiaTerapia CombinatóriaTerapia FototérmicaDomínio/Área Científica::Ciências Médicas::Ciências BiomédicasBreast cancer remains as one of the world's deadliest diseases, a fact that can be explained by the low efficacy and systemic toxicity of the therapies currently in use in the clinic. Recently, researchers have been developing new therapeutic approaches, among which the chemo-photothermal therapy mediated by nanomaterials has been showing promising results, due to its capacity to produce a spatio-temporal controlled anti-cancer effect. During the development of nanomaterials aimed for cancer chemo-photothermal therapy, their efficacy is initially assessed using monolayers of cancer cells (2D in vitro models). The best formulations screened in 2D are then evaluated in tumor bearing mice (in vivo models). However, the 2D in vitro models present some drawbacks, since they are unable to mimic the key features of the in vivo solid tumors. Due to this reason, several nanoformulations that displayed therapeutic efficacy when tested in the 2D in vitro models induce a subpar effect in vivo. To overcome this limitation, spheroids (3D in vitro models) have recently emerged for the screening of nanomedicines. In fact, spheroids are able to reproduce the main properties of the in vivo solid tumors, namely: i) their 3D architecture, ii) microenvironment (gradients of nutrients, pH and gases), iii) cellular and acellular composition, and iv) biochemical and physical resistance patterns to the therapeutics. In this Master thesis, the efficacy of the chemo-photothermal therapy mediated by nanoparticles based on bovine serum albumin functionalized with sulfobetaine methacrylate, co-encapsulating IR780 and Doxorubicin (IR+DOX/SBMA-BSA NPs) was evaluated in 2D in vitro models and spheroids. In 2D in vitro models, it was found that photothermal therapy mediated by nanoparticles loading IR780 (IR/SBMA-BSA NPs and NIR irradiation) reduced cells’ viability to about 58 %, while chemotherapy induced by nanomaterials (IR+DOX/SBMA-BSA NPs) led to a decrease in their viability to 29 %. In addition, the nanoparticles’ mediated chemo-photothermal therapy (IR+DOX/SBMA-BSA NPs and NIR irradiation) achieved a better therapeutic effect by reducing cells’ viability to 1 %. On the other hand, when the therapies were screened on 3D breast cancer models (spheroids), the photothermal therapy mediated by the nanoparticles (IR/SBMA-BSA NPs and NIR irradiation) did not induce an appreciable cytotoxic effect, while the chemotherapy mediated by the nanostructures (IR+DOX/SBMA-BSA NPs) decreased the viability of the spheroids to 42 %. In turn, the chemo-photothermal therapy mediated by the nanomaterials (IR+DOX/SBMA-BSA NPs and NIR irradiation) was able to further reduce the viability of spheroids to 16 %, revealing that this is the most promising therapeutic modality.O cancro de mama prevalece como uma das doenças com maior taxa de mortalidade associada, um facto que pode ser explicado pela baixa eficácia e toxicidade sistémica das terapias usadas presentemente em meio clínico. Recentemente, novas abordagens terapêuticas têm sido desenvolvidas, e entre elas a terapia quimio-fototérmica mediada por nanomateriais tem revelado resultados promissores no tratamento do cancro, devido à sua capacidade para produzir um efeito anticancerígeno controlado no espaço e no tempo. A eficácia terapêutica dos nanomateriais para a quimio-fototermia do cancro tem sido avaliada, até ao momento, usando monocamadas de células cancerígenas (modelo in vitro 2D). A formulação que obteve os melhores resultados in vitro é posteriormente testada em modelos animais portadores de tumor (modelo in vivo). Contudo, os modelos in vitro 2D não mimetizam as principais características dos tumores sólidos encontrados in vivo. Tal facto, faz com que determinadas nanoformulações que exibem eficácia terapêutica in vitro, revelem uma diminuta eficácia in vivo. Para ultrapassar as limitações dos modelos 2D foram desenvolvidos modelos in vitro 3D, conhecidos por esferóides, que têm sido usados na triagem de nanomateriais. Os esferóides são capazes de mimetizar as principais propriedades dos tumores sólidos in vivo, como sejam: i) a sua arquitetura 3D; ii) microambiente tumoral (os gradientes de nutrientes, pH e gases); iii) a composição celular e acelular; e iv) padrões bioquímicos e físicos de resistência às terapias. Nesta dissertação, a eficácia anticancerígena da terapia quimio-fototérmica mediada por nanopartículas à base de albumina de soro bovino funcionalizadas com sulfobetaína metacrilato, co-encapsulando IR780 e Doxorrubicina (IR+DOX/SBMA-BSA NPs) foi avaliada em modelos in vitro 2D e em esferóides. Os resultados obtidos revelaram que a terapia fototérmica mediada pelas nanopartículas encapsulando IR780 (IR/SBMA-BSA NPs irradiadas com luz na região do infravermelho próximo (NIR)) reduziu a viabilidade das células para cerca de 58 %, enquanto que a quimioterapia induzida pelos nanomateriais (IR+DOX/SBMA-BSA NPs) levou a uma diminuição na viabilidade para 29 % nos modelos in vitro 2D. A terapia quimio-fototérmica mediada pelas nanopartículas (IR+DOX/SBMA-BSA NPs e radiação NIR) alcançou o maior efeito terapêutico, tendo reduzido a viabilidade das células cancerígenas para 1 %. Por outro lado, quando estas terapias foram avaliadas em modelos 3D de cancro de mama (esferóides), a terapia fototérmica mediada pelas nanopartículas (IR/SBMA-BSA NPs e radiação NIR) não teve um efeito citotóxico relevante para as células no interior dos esferóides, enquanto que a quimioterapia mediada pelas nanoestruturas (IR+DOX/SBMA-BSA NPs) diminuiu a viabilidade das células presentes nos esferóides para 42 %. Por sua vez, a terapia quimiofototérmica mediada pelos nanomateriais (IR+DOX/SBMA-BSA NPs irradiados com NIR) conseguiu reduzir a viabilidade celular no interior dos esferóides para 16 %. Estes resultados enfatizam que esta última modalidade terapêutica é a mais promissora para futura aplicação em meio clínico. Em suma, os resultados obtidos nesta dissertação demonstraram que os esferóides poderão ter um papel fundamental na triagem de nanomateriais para aplicações terapêuticas. Por outro lado, os esferóides também permitirão reduzir o número de animais usados em experimentação animal, assim como reduzir custos e acelerar o processo de desenvolvimento de novas abordagens terapêuticas.Correia, Ilídio Joaquim SobreiraDiogo, Duarte Miguel de MeloSousa, Ana Rita LimauBibliorumMó, Inês Martins Dias da2023-06-29T00:30:22Z2020-07-162020-06-302020-07-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/10549TID:202545814enginfo: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:RCAAP2023-12-15T09:52:27Zoai:ubibliorum.ubi.pt:10400.6/10549Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:50:28.790594Repositório 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 |
Development of multifunctional phototherapeutic nanoagents |
title |
Development of multifunctional phototherapeutic nanoagents |
spellingShingle |
Development of multifunctional phototherapeutic nanoagents Mó, Inês Martins Dias da Cancro Esferóides Nanopartículas Quimioterapia Terapia Combinatória Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
title_short |
Development of multifunctional phototherapeutic nanoagents |
title_full |
Development of multifunctional phototherapeutic nanoagents |
title_fullStr |
Development of multifunctional phototherapeutic nanoagents |
title_full_unstemmed |
Development of multifunctional phototherapeutic nanoagents |
title_sort |
Development of multifunctional phototherapeutic nanoagents |
author |
Mó, Inês Martins Dias da |
author_facet |
Mó, Inês Martins Dias da |
author_role |
author |
dc.contributor.none.fl_str_mv |
Correia, Ilídio Joaquim Sobreira Diogo, Duarte Miguel de Melo Sousa, Ana Rita Lima uBibliorum |
dc.contributor.author.fl_str_mv |
Mó, Inês Martins Dias da |
dc.subject.por.fl_str_mv |
Cancro Esferóides Nanopartículas Quimioterapia Terapia Combinatória Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
topic |
Cancro Esferóides Nanopartículas Quimioterapia Terapia Combinatória Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
description |
Breast cancer remains as one of the world's deadliest diseases, a fact that can be explained by the low efficacy and systemic toxicity of the therapies currently in use in the clinic. Recently, researchers have been developing new therapeutic approaches, among which the chemo-photothermal therapy mediated by nanomaterials has been showing promising results, due to its capacity to produce a spatio-temporal controlled anti-cancer effect. During the development of nanomaterials aimed for cancer chemo-photothermal therapy, their efficacy is initially assessed using monolayers of cancer cells (2D in vitro models). The best formulations screened in 2D are then evaluated in tumor bearing mice (in vivo models). However, the 2D in vitro models present some drawbacks, since they are unable to mimic the key features of the in vivo solid tumors. Due to this reason, several nanoformulations that displayed therapeutic efficacy when tested in the 2D in vitro models induce a subpar effect in vivo. To overcome this limitation, spheroids (3D in vitro models) have recently emerged for the screening of nanomedicines. In fact, spheroids are able to reproduce the main properties of the in vivo solid tumors, namely: i) their 3D architecture, ii) microenvironment (gradients of nutrients, pH and gases), iii) cellular and acellular composition, and iv) biochemical and physical resistance patterns to the therapeutics. In this Master thesis, the efficacy of the chemo-photothermal therapy mediated by nanoparticles based on bovine serum albumin functionalized with sulfobetaine methacrylate, co-encapsulating IR780 and Doxorubicin (IR+DOX/SBMA-BSA NPs) was evaluated in 2D in vitro models and spheroids. In 2D in vitro models, it was found that photothermal therapy mediated by nanoparticles loading IR780 (IR/SBMA-BSA NPs and NIR irradiation) reduced cells’ viability to about 58 %, while chemotherapy induced by nanomaterials (IR+DOX/SBMA-BSA NPs) led to a decrease in their viability to 29 %. In addition, the nanoparticles’ mediated chemo-photothermal therapy (IR+DOX/SBMA-BSA NPs and NIR irradiation) achieved a better therapeutic effect by reducing cells’ viability to 1 %. On the other hand, when the therapies were screened on 3D breast cancer models (spheroids), the photothermal therapy mediated by the nanoparticles (IR/SBMA-BSA NPs and NIR irradiation) did not induce an appreciable cytotoxic effect, while the chemotherapy mediated by the nanostructures (IR+DOX/SBMA-BSA NPs) decreased the viability of the spheroids to 42 %. In turn, the chemo-photothermal therapy mediated by the nanomaterials (IR+DOX/SBMA-BSA NPs and NIR irradiation) was able to further reduce the viability of spheroids to 16 %, revealing that this is the most promising therapeutic modality. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-07-16 2020-06-30 2020-07-16T00:00:00Z 2023-06-29T00:30:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
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http://hdl.handle.net/10400.6/10549 TID:202545814 |
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eng |
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openAccess |
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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) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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