Development of multifunctional IR780 based nanomaterials for cancer therapy
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/10400.6/10551 |
Resumo: | Breast cancer is a common cause of death among women. This scenario is in part explained by the limitations presented by the treatments currently used in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects. In this way, it is necessary to develop innovative strategies that propel the breast cancer therapy efficacy. Among the different therapeutic strategies under investigation, cancer photothermal therapy mediated by nanomaterials has been showing promising results. This type of therapy takes advantage from the nanomaterials’ physico-chemical properties, that enable their tumor accumulation. Subsequently, the tumor zone is irradiated with Near Infrared (NIR; 750-1000 nm) light and the tumor-homed nanomaterials absorb this energy, releasing it as heat that causes damage to cancer cells. From the plethora of nanomaterials with potential to be applied in cancer photothermal therapy, Graphene Oxide (GO) is a promising candidate due to its NIR absorption and loading capacity. However, as-synthesized GO lacks colloidal stability, i.e., it precipitates when in contact with biological fluids. On the other hand, GO displays a modest photothermal capacity, requiring the use of high doses or intense radiation to achieve the desired therapeutic effect. In the work developed during my MSc, GO was functionalized with an amphiphilic polymer containing [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) brushes and was loaded with IR780 (a NIR photoabsorber), for the first time, to improve its colloidal stability and phototherapeutic capacity, respectively. The obtained results revealed that the SBMA-functionalized GO displays a suitable size distribution, neutral surface charge and an appropriate cytocompatibility. Furthermore, the SBMA-functionalized GO exhibited an improved colloidal stability in biological relevant media (at least up to 48 h), while GO without SBMA functionalization promptly precipitated in the same conditions. By loading IR780 into the SBMA-functionalized GO, its NIR absorption increased by 2.7-fold (at 808 nm), leading to a 1.2-times higher photothermal heating. In in vitro cell studies, the conjugation of NIR irradiation with SBMA-functionalized GO could reduce breast cancer cells’ viability to 73 %. In stark contrast, by combining IR780 loaded SBMA-functionalized GO and NIR radiation, the cancer cells’ viability decreased to 20 %. Overall, the IR780 loaded SBMA-functionalized GO nanomaterials have promising properties for application in breast cancer phototherapy. |
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Development of multifunctional IR780 based nanomaterials for cancer therapyCancroIr780Óxido de GrafenoRevestimentos ZwiteriónicosTerapia FototérmicaDomínio/Área Científica::Ciências Médicas::Ciências BiomédicasBreast cancer is a common cause of death among women. This scenario is in part explained by the limitations presented by the treatments currently used in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects. In this way, it is necessary to develop innovative strategies that propel the breast cancer therapy efficacy. Among the different therapeutic strategies under investigation, cancer photothermal therapy mediated by nanomaterials has been showing promising results. This type of therapy takes advantage from the nanomaterials’ physico-chemical properties, that enable their tumor accumulation. Subsequently, the tumor zone is irradiated with Near Infrared (NIR; 750-1000 nm) light and the tumor-homed nanomaterials absorb this energy, releasing it as heat that causes damage to cancer cells. From the plethora of nanomaterials with potential to be applied in cancer photothermal therapy, Graphene Oxide (GO) is a promising candidate due to its NIR absorption and loading capacity. However, as-synthesized GO lacks colloidal stability, i.e., it precipitates when in contact with biological fluids. On the other hand, GO displays a modest photothermal capacity, requiring the use of high doses or intense radiation to achieve the desired therapeutic effect. In the work developed during my MSc, GO was functionalized with an amphiphilic polymer containing [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) brushes and was loaded with IR780 (a NIR photoabsorber), for the first time, to improve its colloidal stability and phototherapeutic capacity, respectively. The obtained results revealed that the SBMA-functionalized GO displays a suitable size distribution, neutral surface charge and an appropriate cytocompatibility. Furthermore, the SBMA-functionalized GO exhibited an improved colloidal stability in biological relevant media (at least up to 48 h), while GO without SBMA functionalization promptly precipitated in the same conditions. By loading IR780 into the SBMA-functionalized GO, its NIR absorption increased by 2.7-fold (at 808 nm), leading to a 1.2-times higher photothermal heating. In in vitro cell studies, the conjugation of NIR irradiation with SBMA-functionalized GO could reduce breast cancer cells’ viability to 73 %. In stark contrast, by combining IR780 loaded SBMA-functionalized GO and NIR radiation, the cancer cells’ viability decreased to 20 %. Overall, the IR780 loaded SBMA-functionalized GO nanomaterials have promising properties for application in breast cancer phototherapy.O cancro da mama é o tipo de cancro que mais afeta as mulheres. Este cenário deve-se às limitações das terapias utilizadas em meio clínico (quimioterapia e radioterapia), as quais apresentam uma baixa eficácia e efeitos secundários associados. Desta forma, existe uma necessidade premente de desenvolver estratégias inovadoras para o tratamento deste tipo de cancro. Na atualidade, diferentes grupos de investigação estão focados no desenvolvimento de nanomateriais para aplicação na terapia fototérmica do cancro. Este tipo de abordagem terapêutica tem por base a acumulação dos nanomateriais na região tumoral e a sua posterior irradiação com luz com um comprimento de onda na zona do infravermelho próximo (em inglês: Near Infrared (NIR)). Os nanomateriais acumulados no tumor absorvem esta radiação e convertem-na em calor que causa danos nas células cancerígenas. Entre os diferentes nanomateriais desenvolvidos até ao momento, o óxido de grafeno (em inglês: Graphene Oxide (GO)) apresenta-se como um candidato bastante promissor para aplicação na terapia fototérmica do cancro devido à sua capacidade de absorção no NIR e de encapsulamento de biomoléculas. Contudo, o GO apresenta uma baixa estabilidade coloidal, i.e., precipita facilmente quando em contacto com fluídos biológicos. Para além disto, este nanomaterial possui uma baixa capacidade fototérmica, sendo preciso recorrer à administração de elevadas doses ou ao uso de radiação NIR intensa de forma a alcançar um efeito terapêutico adequado. No trabalho de investigação desenvolvido durante o meu segundo ano de mestrado, o GO foi revestido com um polímero anfifílico contendo segmentos de metacrilato de sulfobetaína (SBMA) de forma a aumentar a sua estabilidade coloidal. Posteriormente, o IR780 foi incorporado neste nanomaterial funcionalizado, com o objetivo de melhorar a sua capacidade fototérmica. Os resultados obtidos no presente estudo demonstraram que o GO funcionalizado com SBMA apresenta uma carga de superfície neutra e que é citocompatível. Para além disso, o GO funcionalizado com SBMA manteve a sua distribuição de tamanhos praticamente inalterada, pelo menos durante 48 h, quando em contacto com meio com relevância biológica, possuindo assim uma elevada estabilidade coloidal. Em contraste, os nanomateriais de GO não funcionalizados precipitaram rapidamente em meio de cultura celular. Ao encapsular o IR780 no GO funcionalizado com SBMA, a sua absorção no NIR (a 808 nm) aumentou em cerca de 2,7 vezes, o que lhe permitiu gerar um aumento de temperatura que foi 1,2 vezes maior. Nos estudos in vitro, a conjugação da luz NIR com o GO funcionalizado com SBMA apenas reduziu a viabilidade das células do cancro da mama para 73 %. Em contraste, a combinação da luz NIR com GO funcionalizado com SBMA contendo o IR780, induziu uma redução da viabilidade das células cancerígenas para 20 %. Estes resultados confirmam o potencial deste nanomaterial para aplicação na terapia fototérmica do cancro da mama.Diogo, Duarte Miguel de MeloCorreia, Ilídio Joaquim SobreiraAlves, Cátia GomesuBibliorumLeitao, Miguel Marques2023-09-14T00:30:21Z2020-10-192020-09-152020-10-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/10551TID:202545830enginfo: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:RCAAP2024-11-27T12:34:33Zoai:ubibliorum.ubi.pt:10400.6/10551Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-27T12:34:33Repositório 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 IR780 based nanomaterials for cancer therapy |
title |
Development of multifunctional IR780 based nanomaterials for cancer therapy |
spellingShingle |
Development of multifunctional IR780 based nanomaterials for cancer therapy Leitao, Miguel Marques Cancro Ir780 Óxido de Grafeno Revestimentos Zwiteriónicos Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
title_short |
Development of multifunctional IR780 based nanomaterials for cancer therapy |
title_full |
Development of multifunctional IR780 based nanomaterials for cancer therapy |
title_fullStr |
Development of multifunctional IR780 based nanomaterials for cancer therapy |
title_full_unstemmed |
Development of multifunctional IR780 based nanomaterials for cancer therapy |
title_sort |
Development of multifunctional IR780 based nanomaterials for cancer therapy |
author |
Leitao, Miguel Marques |
author_facet |
Leitao, Miguel Marques |
author_role |
author |
dc.contributor.none.fl_str_mv |
Diogo, Duarte Miguel de Melo Correia, Ilídio Joaquim Sobreira Alves, Cátia Gomes uBibliorum |
dc.contributor.author.fl_str_mv |
Leitao, Miguel Marques |
dc.subject.por.fl_str_mv |
Cancro Ir780 Óxido de Grafeno Revestimentos Zwiteriónicos Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
topic |
Cancro Ir780 Óxido de Grafeno Revestimentos Zwiteriónicos Terapia Fototérmica Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas |
description |
Breast cancer is a common cause of death among women. This scenario is in part explained by the limitations presented by the treatments currently used in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects. In this way, it is necessary to develop innovative strategies that propel the breast cancer therapy efficacy. Among the different therapeutic strategies under investigation, cancer photothermal therapy mediated by nanomaterials has been showing promising results. This type of therapy takes advantage from the nanomaterials’ physico-chemical properties, that enable their tumor accumulation. Subsequently, the tumor zone is irradiated with Near Infrared (NIR; 750-1000 nm) light and the tumor-homed nanomaterials absorb this energy, releasing it as heat that causes damage to cancer cells. From the plethora of nanomaterials with potential to be applied in cancer photothermal therapy, Graphene Oxide (GO) is a promising candidate due to its NIR absorption and loading capacity. However, as-synthesized GO lacks colloidal stability, i.e., it precipitates when in contact with biological fluids. On the other hand, GO displays a modest photothermal capacity, requiring the use of high doses or intense radiation to achieve the desired therapeutic effect. In the work developed during my MSc, GO was functionalized with an amphiphilic polymer containing [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) brushes and was loaded with IR780 (a NIR photoabsorber), for the first time, to improve its colloidal stability and phototherapeutic capacity, respectively. The obtained results revealed that the SBMA-functionalized GO displays a suitable size distribution, neutral surface charge and an appropriate cytocompatibility. Furthermore, the SBMA-functionalized GO exhibited an improved colloidal stability in biological relevant media (at least up to 48 h), while GO without SBMA functionalization promptly precipitated in the same conditions. By loading IR780 into the SBMA-functionalized GO, its NIR absorption increased by 2.7-fold (at 808 nm), leading to a 1.2-times higher photothermal heating. In in vitro cell studies, the conjugation of NIR irradiation with SBMA-functionalized GO could reduce breast cancer cells’ viability to 73 %. In stark contrast, by combining IR780 loaded SBMA-functionalized GO and NIR radiation, the cancer cells’ viability decreased to 20 %. Overall, the IR780 loaded SBMA-functionalized GO nanomaterials have promising properties for application in breast cancer phototherapy. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-10-19 2020-09-15 2020-10-19T00:00:00Z 2023-09-14T00:30:21Z |
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/10400.6/10551 TID:202545830 |
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http://hdl.handle.net/10400.6/10551 |
identifier_str_mv |
TID:202545830 |
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 |
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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) |
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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 |
repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
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1817549651274891264 |