Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.6/9860 |
Resumo: | Breast cancer is a leading cause of death among women. This reality is in part owed to the sub-optimal efficacy and non-specific toxicity of the currently available treatments. In this way, there is an urge need to develop innovative therapies for breast cancer. In the recent years, phototherapies mediated by nanomaterials have been showing promising results in cancer treatment. This type of therapy takes advantage from the ability of nanostructures to accumulate preferentially in the tumor zone. Afterwards, this site is irradiated with near infrared light (NIR) and nanomaterials upon interaction with NIR light, induce a temperature increase (photothermal therapy) or the formation of reactive oxygen species (photodynamic therapy), which can cause damage on cancer cells. Furthermore, nanostructures’ core can also accommodate chemotherapeutic drugs, enabling their application in cancer chemo-phototherapy. Some nanostructures can also emit fluorescence upon exposure to NIR light, thus being promising for imaging applications. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was synthesized and explored for the preparation of polymeric micelles aimed to be used for targeted breast cancer chemo-phototherapy. For such, Doxorubicin (chemotherapeutic agent, DOX) and IR780 (NIR-responsive photothermal agent, photosensitizer and imaging dye) were encapsulated in the micelles’ core. The results revealed that HA-based micelles (HPM) were able to successfully encapsulate IR780 (IR-HPM) and the IR780-DOX combination (IR/DOX-HPM). Furthermore, the encapsulation of IR780 in HPM improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential as well as its cytocompatibility. In the in vitro uptake studies, the fluorescence signals emitted by HPM were explored for cell imaging and the acquired data demonstrated that the nanostructures were preferentially internalized by breast cancer cells. These findings highlight the potential of these nanoformulations for CD44 targeting and cancer diagnosis. Moreover, IR-HPM alone did not induce any noticeable cytotoxicity to breast cancer cells. However, when this formulation was irradiated with NIR light a reduction on cancer cells’ viability was obtained. The combined effect of IR/DOX-HPM and NIR light further decreased cancer cells’ viability. Overall, based on the results obtained we can state that HPM are promising nanoplatforms for targeted chemo-phototherapy and imaging. |
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Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancroCancroMicelas DirecionadasQuimioterapiaTerapia CombinatóriaTerapia FototérmicaDomínio/Área Científica::Ciências Médicas::Ciências BiomédicasBreast cancer is a leading cause of death among women. This reality is in part owed to the sub-optimal efficacy and non-specific toxicity of the currently available treatments. In this way, there is an urge need to develop innovative therapies for breast cancer. In the recent years, phototherapies mediated by nanomaterials have been showing promising results in cancer treatment. This type of therapy takes advantage from the ability of nanostructures to accumulate preferentially in the tumor zone. Afterwards, this site is irradiated with near infrared light (NIR) and nanomaterials upon interaction with NIR light, induce a temperature increase (photothermal therapy) or the formation of reactive oxygen species (photodynamic therapy), which can cause damage on cancer cells. Furthermore, nanostructures’ core can also accommodate chemotherapeutic drugs, enabling their application in cancer chemo-phototherapy. Some nanostructures can also emit fluorescence upon exposure to NIR light, thus being promising for imaging applications. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was synthesized and explored for the preparation of polymeric micelles aimed to be used for targeted breast cancer chemo-phototherapy. For such, Doxorubicin (chemotherapeutic agent, DOX) and IR780 (NIR-responsive photothermal agent, photosensitizer and imaging dye) were encapsulated in the micelles’ core. The results revealed that HA-based micelles (HPM) were able to successfully encapsulate IR780 (IR-HPM) and the IR780-DOX combination (IR/DOX-HPM). Furthermore, the encapsulation of IR780 in HPM improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential as well as its cytocompatibility. In the in vitro uptake studies, the fluorescence signals emitted by HPM were explored for cell imaging and the acquired data demonstrated that the nanostructures were preferentially internalized by breast cancer cells. These findings highlight the potential of these nanoformulations for CD44 targeting and cancer diagnosis. Moreover, IR-HPM alone did not induce any noticeable cytotoxicity to breast cancer cells. However, when this formulation was irradiated with NIR light a reduction on cancer cells’ viability was obtained. The combined effect of IR/DOX-HPM and NIR light further decreased cancer cells’ viability. Overall, based on the results obtained we can state that HPM are promising nanoplatforms for targeted chemo-phototherapy and imaging.O cancro da mama é uma das principais causas de morte nas mulheres em todo o mundo. Esta realidade deve-se em parte às limitações dos tratamentos usados na clínica, os quais apresentam baixa eficácia e induzem toxicidade não específica. Deste modo, existe uma necessidade crescente de desenvolver terapias inovadoras para o cancro. Nos últimos anos, as fototerapias mediadas por nanomateriais têm demonstrado resultados promissores no tratamento do cancro. Este tipo de terapias tira proveito da capacidade das nanoestruturas para se acumularem preferencialmente na zona do tumor e posteriormente, ao serem irradiadas com luz com um comprimento de onda na zona do infravermelho próximo (NIR), produzirem um aumento de temperatura (terapia fototérmica) ou espécies reativas de oxigénio (terapia fotodinâmica), os quais podem induzir danos nas células cancerígenas. Para além disto, é também possível encapsular fármacos quimioterapêuticos no interior deste tipo de nanoestruturas, permitindo a sua utilização como agentes de quimio-fototerapia. Algumas nanoestruturas, após interação com a luz NIR, apresentam capacidade de emitir fluorescência, o que permite equacionar a sua utilização em imagiologia. Na presente tese, desenvolveu-se um polímero anfifílico baseado em ácido hialurónico (HA) para formular micelas poliméricas concebidas para aplicação na quimio-fototerapia direcionada para o cancro da mama. Durante o processo de produção das micelas, a Doxorrubicina (agente quimioterapêutico) e o IR780 (agente responsivo à luz NIR com capacidade fototérmica, de fotossensibilização e de contaste de imagiologia) foram encapsulados no núcleo da micela. Os resultados obtidos revelaram que as micelas baseadas em HA (HPM) conseguem encapsular o IR780 (IR-HPM) e ainda permitem efetuar a co-encapsulação de IR780-Doxorrubicina (IR/DOX-HPM). Para além disto, verificou-se que a encapsulação do IR780 nas HPM aumenta a sua absorção (a 808 nm), em cerca de 2,2 vezes, comparativamente com o IR780 livre (não encapsulado), o que permite incrementar o potencial fototérmico das HPM. Por outro lado, a encapsulação do IR780 nos nanotransportadores também melhorou a sua citocompatibilidade. Nos ensaios de internalização in vitro, a fluorescência emitida pelas HPM foi utilizada para visualizar as células, tendo-se verificado que as HPM foram preferencialmente internalizadas pelas células do cancro da mama comparativamente com as células saudáveis. Estes resultados evidenciam o potencial destas nanoformulações para diagnóstico de cancro, bem como a sua capacidade de serem reconhecidas pelos recetores CD44 sobreexpressos na superfície das células cancerígenas. Nos ensaios de eficácia terapêutica, observou-se que as IR-HPM não causam efeitos citotóxicos consideráveis nas células do cancro da mama, enquanto a sua combinação com luz NIR induz uma redução da viabilidade celular. Por outro lado, a aplicação combinada das IR/DOX-HPM e luz NIR provocou uma diminuição ainda mais acentuada da viabilidade celular. Em suma, as HPM são nanoplataformas que apresentam propriedades promissoras para a sua aplicação na quimio-fototerapia direcionada para o cancro da mama e imagiologia.Correia, Ilídio Joaquim SobreiraDiogo, Duarte Miguel de MelouBibliorumAlves, Cátia Gomes2021-06-20T00:30:16Z2018-07-202018-06-202018-07-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/9860TID:202354016enginfo: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:RCAAP2024-11-27T12:32:52Zoai:ubibliorum.ubi.pt:10400.6/9860Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-27T12:32:52Repositório 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 |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
title |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
spellingShingle |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro Alves, Cátia Gomes Cancro Micelas Direcionadas Quimioterapia Terapia Combinatória Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
title_short |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
title_full |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
title_fullStr |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
title_full_unstemmed |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
title_sort |
Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro |
author |
Alves, Cátia Gomes |
author_facet |
Alves, Cátia Gomes |
author_role |
author |
dc.contributor.none.fl_str_mv |
Correia, Ilídio Joaquim Sobreira Diogo, Duarte Miguel de Melo uBibliorum |
dc.contributor.author.fl_str_mv |
Alves, Cátia Gomes |
dc.subject.por.fl_str_mv |
Cancro Micelas Direcionadas Quimioterapia Terapia Combinatória Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
topic |
Cancro Micelas Direcionadas Quimioterapia Terapia Combinatória Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
description |
Breast cancer is a leading cause of death among women. This reality is in part owed to the sub-optimal efficacy and non-specific toxicity of the currently available treatments. In this way, there is an urge need to develop innovative therapies for breast cancer. In the recent years, phototherapies mediated by nanomaterials have been showing promising results in cancer treatment. This type of therapy takes advantage from the ability of nanostructures to accumulate preferentially in the tumor zone. Afterwards, this site is irradiated with near infrared light (NIR) and nanomaterials upon interaction with NIR light, induce a temperature increase (photothermal therapy) or the formation of reactive oxygen species (photodynamic therapy), which can cause damage on cancer cells. Furthermore, nanostructures’ core can also accommodate chemotherapeutic drugs, enabling their application in cancer chemo-phototherapy. Some nanostructures can also emit fluorescence upon exposure to NIR light, thus being promising for imaging applications. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was synthesized and explored for the preparation of polymeric micelles aimed to be used for targeted breast cancer chemo-phototherapy. For such, Doxorubicin (chemotherapeutic agent, DOX) and IR780 (NIR-responsive photothermal agent, photosensitizer and imaging dye) were encapsulated in the micelles’ core. The results revealed that HA-based micelles (HPM) were able to successfully encapsulate IR780 (IR-HPM) and the IR780-DOX combination (IR/DOX-HPM). Furthermore, the encapsulation of IR780 in HPM improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential as well as its cytocompatibility. In the in vitro uptake studies, the fluorescence signals emitted by HPM were explored for cell imaging and the acquired data demonstrated that the nanostructures were preferentially internalized by breast cancer cells. These findings highlight the potential of these nanoformulations for CD44 targeting and cancer diagnosis. Moreover, IR-HPM alone did not induce any noticeable cytotoxicity to breast cancer cells. However, when this formulation was irradiated with NIR light a reduction on cancer cells’ viability was obtained. The combined effect of IR/DOX-HPM and NIR light further decreased cancer cells’ viability. Overall, based on the results obtained we can state that HPM are promising nanoplatforms for targeted chemo-phototherapy and imaging. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-07-20 2018-06-20 2018-07-20T00:00:00Z 2021-06-20T00:30:16Z |
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/10400.6/9860 TID:202354016 |
url |
http://hdl.handle.net/10400.6/9860 |
identifier_str_mv |
TID:202354016 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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.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 |
mluisa.alvim@gmail.com |
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1817549645139673088 |