Development of graphene oxide based nanomaterials for cancer therapy

Detalhes bibliográficos
Autor(a) principal: Sousa, Ana Rita Lima de
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/10400.6/9771
Resumo: Breast cancer is one of the leading causes of death in the world, affecting mostly women. The most common treatments for this disease include radio- and chemo-therapies. However, these therapeutic approaches have a sub-optimal efficacy and can induce adverse side effects to patients. In this way, there is an urgent demand for the development of novel breast cancer treatments. To improve the breast cancer treatment, researchers are developing new therapeutic approaches. In particular, photothermal therapy (PTT) mediated by nanomaterials has captured the attention of researchers and clinicians. This type of therapy takes advantage from the physicochemical and optical properties of some light-responsive nanostructures. These can accumulate preferentially in the tumor zone, and induce, after external irradiation with near infrared (NIR) light, a temperature increase that can damage cancer cells. In this thesis, reduced graphene oxide (rGO) was produced by using an environmentally-friendly method. Then rGO was functionalized with a novel hyaluronic acid (HA)-based amphiphilic polymer to be applied in targeted breast cancer PTT. HA was selected due to its hydrophilic character and targeting capacity to the CD44 receptors, which are overexpressed on breast cancer cells’ membrane. The obtained results revealed that the treatment of graphene oxide with L-ascorbic acid (3 mM) for 60 minutes at 80 °C is ideal considering the NIR absorption and the size distribution of the obtained materials. Then, rGO was functionalized with the HA-based amphiphilic polymer through non-covalent interactions. The functionalization of rGO improved its stability, cytocompatibility, and internalization by CD44 overexpressed by breast cancer cells, which indicates the targeting capacity of this nanoformulation. Furthermore, the on-demand PTT mediated by HA functionalized rGO induced cancer cells’ death, thereby confirming the potential of this nanoformulation for targeted breast cancer therapy.
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spelling Development of graphene oxide based nanomaterials for cancer therapyÁcido HialurónicoEfeito FototérmicoMateriais 2dQuímica EcológicaTerapia DirecionadaDomínio/Área Científica::Ciências Médicas::Ciências BiomédicasBreast cancer is one of the leading causes of death in the world, affecting mostly women. The most common treatments for this disease include radio- and chemo-therapies. However, these therapeutic approaches have a sub-optimal efficacy and can induce adverse side effects to patients. In this way, there is an urgent demand for the development of novel breast cancer treatments. To improve the breast cancer treatment, researchers are developing new therapeutic approaches. In particular, photothermal therapy (PTT) mediated by nanomaterials has captured the attention of researchers and clinicians. This type of therapy takes advantage from the physicochemical and optical properties of some light-responsive nanostructures. These can accumulate preferentially in the tumor zone, and induce, after external irradiation with near infrared (NIR) light, a temperature increase that can damage cancer cells. In this thesis, reduced graphene oxide (rGO) was produced by using an environmentally-friendly method. Then rGO was functionalized with a novel hyaluronic acid (HA)-based amphiphilic polymer to be applied in targeted breast cancer PTT. HA was selected due to its hydrophilic character and targeting capacity to the CD44 receptors, which are overexpressed on breast cancer cells’ membrane. The obtained results revealed that the treatment of graphene oxide with L-ascorbic acid (3 mM) for 60 minutes at 80 °C is ideal considering the NIR absorption and the size distribution of the obtained materials. Then, rGO was functionalized with the HA-based amphiphilic polymer through non-covalent interactions. The functionalization of rGO improved its stability, cytocompatibility, and internalization by CD44 overexpressed by breast cancer cells, which indicates the targeting capacity of this nanoformulation. Furthermore, the on-demand PTT mediated by HA functionalized rGO induced cancer cells’ death, thereby confirming the potential of this nanoformulation for targeted breast cancer therapy.O cancro da mama é uma das principais causas de morte em todo o mundo, afetando principalmente as mulheres. Os tratamentos mais comuns para esta doença incluem a radioterapia e a quimioterapia. No entanto, estas abordagens terapêuticas apresentam uma baixa eficácia e podem, também, induzir efeitos secundários adversos nos pacientes. Desta forma, existe uma enorme necessidade em desenvolver novos tratamentos mais eficazes para o cancro da mama. Neste contexto, diferentes investigadores estão a desenvolver novas abordagens terapêuticas. Em particular, a terapia fototérmica mediada por nanomateriais tem recebido um interesse crescente por parte dos investigadores e profissionais de saúde. Esta abordagem tira partido das propriedades físico-químicas e óticas de alguns tipos de nanomateriais. Estas nanoestruturas responsivas à luz conseguem acumular-se preferencialmente na zona tumoral e posteriormente induzir, após irradiação com luz com um comprimento de onda na região do infravermelho próximo (NIR), um aumento de temperatura que pode danificar as células cancerígenas. Nesta dissertação, materiais à base de óxido de grafeno reduzido (rGO) foram produzidos através de um método de redução ecológico e funcionalizados com um novo polímero anfifílico à base de ácido hialurónico (HA) para aplicação na terapia fototérmica do cancro da mama. O HA foi escolhido devido ao seu carácter hidrofílico e por possuir capacidade de direcionamento para os recetores CD44, que são sobreexpressos na membrana citoplasmática das células do cancro da mama. Os resultados obtidos revelaram que o tratamento do óxido de grafeno com ácido L-ascórbico (3 mM), durante 60 minutos, a 80 ºC, constituem as condições ideais de redução tendo em conta a absorção no NIR apresentada pelo rGO e a distribuição de tamanhos dos materiais obtidos. Posteriormente, a funcionalização do rGO com o polímero anfifílico à base de HA foi efetuada através de interações não-covalentes. A funcionalização melhorou a estabilidade, citocompatibilidade e internalização dos nanomateriais pelas células do cancro da mama que sobreexpressam o recetor CD44, o que confirma a capacidade de direcionamento desta nanoformulação. Adicionalmente, a terapia fototérmica mediada pelo rGO funcionalizado induziu a morte das células cancerígenas, confirmando assim o potencial desta nanoformulação para aplicação na terapia direcionada do cancro da mama.Correia, Ilídio Joaquim SobreiraDiogo, Duarte Miguel de MelouBibliorumSousa, Ana Rita Lima de2021-06-20T00:30:15Z2018-07-202018-06-202018-07-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/9771TID:202353958enginfo: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:RCAAP2023-12-20T02:30:37Zoai:ubibliorum.ubi.pt:10400.6/9771Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:49:51.360180Repositório 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 graphene oxide based nanomaterials for cancer therapy
title Development of graphene oxide based nanomaterials for cancer therapy
spellingShingle Development of graphene oxide based nanomaterials for cancer therapy
Sousa, Ana Rita Lima de
Ácido Hialurónico
Efeito Fototérmico
Materiais 2d
Química Ecológica
Terapia Direcionada
Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas
title_short Development of graphene oxide based nanomaterials for cancer therapy
title_full Development of graphene oxide based nanomaterials for cancer therapy
title_fullStr Development of graphene oxide based nanomaterials for cancer therapy
title_full_unstemmed Development of graphene oxide based nanomaterials for cancer therapy
title_sort Development of graphene oxide based nanomaterials for cancer therapy
author Sousa, Ana Rita Lima de
author_facet Sousa, Ana Rita Lima de
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 Sousa, Ana Rita Lima de
dc.subject.por.fl_str_mv Ácido Hialurónico
Efeito Fototérmico
Materiais 2d
Química Ecológica
Terapia Direcionada
Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas
topic Ácido Hialurónico
Efeito Fototérmico
Materiais 2d
Química Ecológica
Terapia Direcionada
Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas
description Breast cancer is one of the leading causes of death in the world, affecting mostly women. The most common treatments for this disease include radio- and chemo-therapies. However, these therapeutic approaches have a sub-optimal efficacy and can induce adverse side effects to patients. In this way, there is an urgent demand for the development of novel breast cancer treatments. To improve the breast cancer treatment, researchers are developing new therapeutic approaches. In particular, photothermal therapy (PTT) mediated by nanomaterials has captured the attention of researchers and clinicians. This type of therapy takes advantage from the physicochemical and optical properties of some light-responsive nanostructures. These can accumulate preferentially in the tumor zone, and induce, after external irradiation with near infrared (NIR) light, a temperature increase that can damage cancer cells. In this thesis, reduced graphene oxide (rGO) was produced by using an environmentally-friendly method. Then rGO was functionalized with a novel hyaluronic acid (HA)-based amphiphilic polymer to be applied in targeted breast cancer PTT. HA was selected due to its hydrophilic character and targeting capacity to the CD44 receptors, which are overexpressed on breast cancer cells’ membrane. The obtained results revealed that the treatment of graphene oxide with L-ascorbic acid (3 mM) for 60 minutes at 80 °C is ideal considering the NIR absorption and the size distribution of the obtained materials. Then, rGO was functionalized with the HA-based amphiphilic polymer through non-covalent interactions. The functionalization of rGO improved its stability, cytocompatibility, and internalization by CD44 overexpressed by breast cancer cells, which indicates the targeting capacity of this nanoformulation. Furthermore, the on-demand PTT mediated by HA functionalized rGO induced cancer cells’ death, thereby confirming the potential of this nanoformulation for targeted breast cancer therapy.
publishDate 2018
dc.date.none.fl_str_mv 2018-07-20
2018-06-20
2018-07-20T00:00:00Z
2021-06-20T00:30:15Z
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