Development of multifunctional graphene oxide based nanomaterials for cancer therapy

Detalhes bibliográficos
Autor(a) principal: Melo, Bruna Daniela Lopes
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/10400.6/10801
Resumo: Breast cancer remains as one of the deadliest diseases affecting the worldwide population. The high mortality rate exhibited by this disease can be attributed to the limitations of the treatments currently in use in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects in patients. Therefore, there is an urgent demand for innovative therapeutic approaches that can enhance breast cancer survival rates. Recently, nanomaterials’ mediated Photothermal Therapy (PTT) has been showing promising results for cancer treatment. This therapeutic modality employs nanostructures that, due to their specific set of physicochemical characteristics, can accumulate at the tumor site. Afterwards, this zone is irradiated with Near Infrared (NIR) light and the tumor-homed nanomaterials induce a local temperature increase (hyperthermia) that can induce damage to cancer cells. Among the several nanomaterials with potential for cancer PTT, Graphene Oxide (GO) has been extensively investigated due to its absorption in the NIR. After interacting with this radiation, GO produces a temperature increase that can cause damage to cancer cells. In addition, this nanomaterial has an aromatic matrix that can be used to encapsulate a wide variety of compounds, thus having a great versatility. However, the direct application of GO in cancer PTT is limited by two factors: i) the low colloidal stability of GO, which causes its precipitation in biological fluids, and ii) the poor photothermal capacity of GO, which leads to the use of high doses/intense radiation in order to achieve an adequate therapeutic effect. In this MSc research work, GO was functionalized with an albumin based amphiphilic coating containing Sulfobetaine Methacrylate (SBMA) brushes (SBMA-g-BSA) and was loaded with IR780, with the intent to improve its colloidal stability and photothermal capacity, respectively. The results revealed that GO functionalized with SBMA-g-BSA (SBMA-BSA/GO) presents an adequate size distribution and cytocompatibility for cancer-related applications. When in contact with biologically relevant media, the size of the SBMA-functionalized GO derivatives only increased by 8 % after 48 h. In the same condition and period, the non-SBMA functionalized GO (BSA coated GO) suffered a 31 % increase in its size. By loading IR780 into SBMA-BSA/GO (IR/SBMA-BSA/GO), the nanomaterials’ NIR absorption increased by 5.6-fold. In this way, the IR/SBMA-BSA/GO could produce a up to 2-times higher photoinduced heat than SBMA-BSA/GO. In in vitro cell studies, the combination of NIR light with SBMA-BSA/GO did not induce photocytotoxicity on breast cancer cells. In stark contrast, the interaction of IR/SBMA-BSA/GO with NIR light caused the ablation of cancer cells (cell viability < 2 %). Overall, IR/SBMA-BSA/GO displays a greatly improved colloidal stability and phototherapeutic capacity, being a promising hybrid nanomaterial for application in the PTT of breast cancer cells.
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spelling Development of multifunctional graphene oxide based nanomaterials for cancer therapyIr780Óxido de GrafenoRevestimentos Baseados Em ProteínasRevestimentos ZwiteriónicosTerapia do CancroTerapia FototérmicaDomínio/Área Científica::Ciências Médicas::Ciências BiomédicasBreast cancer remains as one of the deadliest diseases affecting the worldwide population. The high mortality rate exhibited by this disease can be attributed to the limitations of the treatments currently in use in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects in patients. Therefore, there is an urgent demand for innovative therapeutic approaches that can enhance breast cancer survival rates. Recently, nanomaterials’ mediated Photothermal Therapy (PTT) has been showing promising results for cancer treatment. This therapeutic modality employs nanostructures that, due to their specific set of physicochemical characteristics, can accumulate at the tumor site. Afterwards, this zone is irradiated with Near Infrared (NIR) light and the tumor-homed nanomaterials induce a local temperature increase (hyperthermia) that can induce damage to cancer cells. Among the several nanomaterials with potential for cancer PTT, Graphene Oxide (GO) has been extensively investigated due to its absorption in the NIR. After interacting with this radiation, GO produces a temperature increase that can cause damage to cancer cells. In addition, this nanomaterial has an aromatic matrix that can be used to encapsulate a wide variety of compounds, thus having a great versatility. However, the direct application of GO in cancer PTT is limited by two factors: i) the low colloidal stability of GO, which causes its precipitation in biological fluids, and ii) the poor photothermal capacity of GO, which leads to the use of high doses/intense radiation in order to achieve an adequate therapeutic effect. In this MSc research work, GO was functionalized with an albumin based amphiphilic coating containing Sulfobetaine Methacrylate (SBMA) brushes (SBMA-g-BSA) and was loaded with IR780, with the intent to improve its colloidal stability and photothermal capacity, respectively. The results revealed that GO functionalized with SBMA-g-BSA (SBMA-BSA/GO) presents an adequate size distribution and cytocompatibility for cancer-related applications. When in contact with biologically relevant media, the size of the SBMA-functionalized GO derivatives only increased by 8 % after 48 h. In the same condition and period, the non-SBMA functionalized GO (BSA coated GO) suffered a 31 % increase in its size. By loading IR780 into SBMA-BSA/GO (IR/SBMA-BSA/GO), the nanomaterials’ NIR absorption increased by 5.6-fold. In this way, the IR/SBMA-BSA/GO could produce a up to 2-times higher photoinduced heat than SBMA-BSA/GO. In in vitro cell studies, the combination of NIR light with SBMA-BSA/GO did not induce photocytotoxicity on breast cancer cells. In stark contrast, the interaction of IR/SBMA-BSA/GO with NIR light caused the ablation of cancer cells (cell viability < 2 %). Overall, IR/SBMA-BSA/GO displays a greatly improved colloidal stability and phototherapeutic capacity, being a promising hybrid nanomaterial for application in the PTT of breast cancer cells.O cancro da mama é uma das doenças com maior taxa de mortalidade associada. Este facto está relacionado com a baixa eficácia das terapias, como por exemplo a radio e a quimioterapia, usadas em meio clínico. Para ultrapassar esta baixa eficácia e os efeitos secundários associados, os investigadores têm procurado desenvolver novas abordagens para o tratamento do cancro da mama. Recentemente, a Terapia Fototérmica (do inglês Photothermal Therapy (PTT)) mediada por nanomateriais tem apresentado resultados bastante promissores. Nesta modalidade terapêutica, os nanomateriais, devido às suas características físico-químicas, conseguem acumular-se no tumor. Posteriormente, a zona tumoral é irradiada com luz com comprimento de onda na região do infravermelho próximo (do inglês Near Infrared (NIR)). A interação da luz NIR com os nanomateriais acumulados no tumor induz um aumento de temperatura local (hipertermia), que pode causar a morte das células cancerígenas. De entre os vários nanomateriais que têm sido estudados para aplicação na PTT do cancro, o Óxido de Grafeno (do inglês Graphene Oxide (GO)) tem sido amplamente explorado devido à sua absorção no NIR. Após interação com esta radiação, o GO produz um aumento de temperatura que pode causar danos celulares. Para além disto, este nanomaterial tem uma matriz aromática que lhe permite encapsular uma grande variedade de compostos, exibindo, portanto, uma grande versatilidade. No entanto, a aplicação direta do GO na PTT do cancro é limitada por dois fatores: i) a baixa estabilidade coloidal do GO, o que faz com que precipite em fluidos biológicos, e ii) a fraca capacidade fototérmica do GO, o que conduz à administração de doses elevadas/uso de radiação intensa para alcançar um efeito terapêutico adequado. No trabalho de investigação que desenvolvi durante o meu mestrado, o GO foi funcionalizado com um conjugado de Metacrilato de Sulfobetaína-Albumina de Soro Bovino (SBMA-g-BSA) e o IR780 foi encapsulado na sua estrutura, com o intuito de melhorar a sua estabilidade coloidal e capacidade fototérmica, respetivamente. Os resultados obtidos mostraram que o GO funcionalizado com SBMA-g-BSA (SBMA-BSA/GO) apresenta uma distribuição de tamanhos e citocompatibilidade adequadas para a sua aplicação na terapia do cancro. Quando o SBMA-BSA/GO foi colocado em contacto com meio com relevância biológica, o seu tamanho apenas aumentou em 5 % durante 48 h. Por outro lado, o GO revestido apenas com BSA (sem funcionalização de SBMA) teve um acréscimo de 31 % no seu tamanho neste período. Ao encapsular o IR780 na estrutura grafítica do GO, a absorção deste nanomaterial na zona do NIR aumentou em cerca de 5,6 vezes, o que permitiu duplicar a sua capacidade fototérmica. Nos estudos realizados in vitro, a viabilidade das células do cancro da mama não foi afetada pela sua incubação com SBMA-BSA/GO juntamente com radiação NIR. Por outro lado, a combinação de IR/SBMA-BSA/GO com irradiação NIR induziu a morte destas células (viabilidade celular inferior a 2 %). Assim, o IR/SBMA-BSA/GO apresenta estabilidade coloidal e capacidade fototerapêutica melhoradas, sendo um nanohíbrido promissor para a aplicação na PTT do cancro da mama.Diogo, Duarte Miguel de MeloCorreia, Ilídio Joaquim SobreiraSousa, Ana Rita LimauBibliorumMelo, Bruna Daniela Lopes2023-09-18T00:30:36Z2020-10-192020-09-172020-10-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/10801TID:202558169enginfo: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:RCAAP2024-11-27T12:35:05Zoai:ubibliorum.ubi.pt:10400.6/10801Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-27T12:35:05Repositório 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 graphene oxide based nanomaterials for cancer therapy
title Development of multifunctional graphene oxide based nanomaterials for cancer therapy
spellingShingle Development of multifunctional graphene oxide based nanomaterials for cancer therapy
Melo, Bruna Daniela Lopes
Ir780
Óxido de Grafeno
Revestimentos Baseados Em Proteínas
Revestimentos Zwiteriónicos
Terapia do Cancro
Terapia Fototérmica
Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas
title_short Development of multifunctional graphene oxide based nanomaterials for cancer therapy
title_full Development of multifunctional graphene oxide based nanomaterials for cancer therapy
title_fullStr Development of multifunctional graphene oxide based nanomaterials for cancer therapy
title_full_unstemmed Development of multifunctional graphene oxide based nanomaterials for cancer therapy
title_sort Development of multifunctional graphene oxide based nanomaterials for cancer therapy
author Melo, Bruna Daniela Lopes
author_facet Melo, Bruna Daniela Lopes
author_role author
dc.contributor.none.fl_str_mv Diogo, Duarte Miguel de Melo
Correia, Ilídio Joaquim Sobreira
Sousa, Ana Rita Lima
uBibliorum
dc.contributor.author.fl_str_mv Melo, Bruna Daniela Lopes
dc.subject.por.fl_str_mv Ir780
Óxido de Grafeno
Revestimentos Baseados Em Proteínas
Revestimentos Zwiteriónicos
Terapia do Cancro
Terapia Fototérmica
Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas
topic Ir780
Óxido de Grafeno
Revestimentos Baseados Em Proteínas
Revestimentos Zwiteriónicos
Terapia do Cancro
Terapia Fototérmica
Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas
description Breast cancer remains as one of the deadliest diseases affecting the worldwide population. The high mortality rate exhibited by this disease can be attributed to the limitations of the treatments currently in use in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects in patients. Therefore, there is an urgent demand for innovative therapeutic approaches that can enhance breast cancer survival rates. Recently, nanomaterials’ mediated Photothermal Therapy (PTT) has been showing promising results for cancer treatment. This therapeutic modality employs nanostructures that, due to their specific set of physicochemical characteristics, can accumulate at the tumor site. Afterwards, this zone is irradiated with Near Infrared (NIR) light and the tumor-homed nanomaterials induce a local temperature increase (hyperthermia) that can induce damage to cancer cells. Among the several nanomaterials with potential for cancer PTT, Graphene Oxide (GO) has been extensively investigated due to its absorption in the NIR. After interacting with this radiation, GO produces a temperature increase that can cause damage to cancer cells. In addition, this nanomaterial has an aromatic matrix that can be used to encapsulate a wide variety of compounds, thus having a great versatility. However, the direct application of GO in cancer PTT is limited by two factors: i) the low colloidal stability of GO, which causes its precipitation in biological fluids, and ii) the poor photothermal capacity of GO, which leads to the use of high doses/intense radiation in order to achieve an adequate therapeutic effect. In this MSc research work, GO was functionalized with an albumin based amphiphilic coating containing Sulfobetaine Methacrylate (SBMA) brushes (SBMA-g-BSA) and was loaded with IR780, with the intent to improve its colloidal stability and photothermal capacity, respectively. The results revealed that GO functionalized with SBMA-g-BSA (SBMA-BSA/GO) presents an adequate size distribution and cytocompatibility for cancer-related applications. When in contact with biologically relevant media, the size of the SBMA-functionalized GO derivatives only increased by 8 % after 48 h. In the same condition and period, the non-SBMA functionalized GO (BSA coated GO) suffered a 31 % increase in its size. By loading IR780 into SBMA-BSA/GO (IR/SBMA-BSA/GO), the nanomaterials’ NIR absorption increased by 5.6-fold. In this way, the IR/SBMA-BSA/GO could produce a up to 2-times higher photoinduced heat than SBMA-BSA/GO. In in vitro cell studies, the combination of NIR light with SBMA-BSA/GO did not induce photocytotoxicity on breast cancer cells. In stark contrast, the interaction of IR/SBMA-BSA/GO with NIR light caused the ablation of cancer cells (cell viability < 2 %). Overall, IR/SBMA-BSA/GO displays a greatly improved colloidal stability and phototherapeutic capacity, being a promising hybrid nanomaterial for application in the PTT of breast cancer cells.
publishDate 2020
dc.date.none.fl_str_mv 2020-10-19
2020-09-17
2020-10-19T00:00:00Z
2023-09-18T00:30:36Z
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TID:202558169
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instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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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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