Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells

Detalhes bibliográficos
Autor(a) principal: Meireis, André Miguel Forte
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/153497
Resumo: Cancer is on the verge of becoming the number one cause of deaths worldwide, despite all the efforts and numerous studies regarding the molecular mechanisms underlying carcino- genesis and the development of new approaches to cancer therapy. Current therapies still have major downsides and to overcome them it is of high importance to develop novel approaches that offer better selectivity, minimizing the death of healthy cells, and that are able to overcome the resistance of cancer cells. Autophagy is one of the main cellular mechanisms used by cancer cells to produce enough energy for tumor development and to also resist the effects from certain therapeutic drugs. This mechanism is extremely reliant on the lysosomes and if these were to be disrupted so would the mechanism. In this work we report the study of antibody functionalized gold nanoparticles as potential photothermal agents for specific photoirradiation of the lysosomes in cancer cells. Antibody functionalized gold nanoparticles for specific targeting of the lysosomal mem- brane were synthesized, and cellular uptake and phothotermia assays were performed in a colorectal cancer cell line. Cellular uptake assays revealed increased particle uptake and lyso- somal accumulation of antibody functionalized gold nanoparticles whilst cell viability studies regarding photothermia assays showed no effect on cellular viability. Results demonstrated the active targeting of lysosomes by the synthesized nanoparticles, validating their potential as targeting agents. Future work is needed to evaluate the potential of these particles as possible photothermal agents.
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spelling Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cellsCancerAutophagyGold NanoparticlesCellular UptakeLysosomesPhotothermiaDomínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e TecnologiasCancer is on the verge of becoming the number one cause of deaths worldwide, despite all the efforts and numerous studies regarding the molecular mechanisms underlying carcino- genesis and the development of new approaches to cancer therapy. Current therapies still have major downsides and to overcome them it is of high importance to develop novel approaches that offer better selectivity, minimizing the death of healthy cells, and that are able to overcome the resistance of cancer cells. Autophagy is one of the main cellular mechanisms used by cancer cells to produce enough energy for tumor development and to also resist the effects from certain therapeutic drugs. This mechanism is extremely reliant on the lysosomes and if these were to be disrupted so would the mechanism. In this work we report the study of antibody functionalized gold nanoparticles as potential photothermal agents for specific photoirradiation of the lysosomes in cancer cells. Antibody functionalized gold nanoparticles for specific targeting of the lysosomal mem- brane were synthesized, and cellular uptake and phothotermia assays were performed in a colorectal cancer cell line. Cellular uptake assays revealed increased particle uptake and lyso- somal accumulation of antibody functionalized gold nanoparticles whilst cell viability studies regarding photothermia assays showed no effect on cellular viability. Results demonstrated the active targeting of lysosomes by the synthesized nanoparticles, validating their potential as targeting agents. Future work is needed to evaluate the potential of these particles as possible photothermal agents.O cancro está prestes a tornar-se a causa número um de mortes em todo o mundo, apesar de todos os esforços e inúmeros estudos sobre os mecanismos moleculares subjacentes à carcinogénese e o desenvolvimento de novas abordagens para a terapia do cancro. As tera- pias atuais ainda apresentam grandes desvantagens e para superá-las é de grande importância desenvolver novas abordagens que ofereçam melhor seletividade, minimizando a morte de células saudáveis, e que sejam capazes de superar a resistência das células cancerígenas. A autofagia é um dos principais mecanismos celulares utilizados pelas células cancerí- genas para produzir energia suficiente para o desenvolvimento do tumor e para resistir aos efeitos de certas drogas terapêuticas. Este mecanismo é extremamente dependente dos lisos- somas e, se estes fossem rompidos, o funcionamento deste mecanismo seria afetado. Neste trabalho relatamos o estudo de nanopartículas de ouro funcionalizadas com anticorpos como potenciais agentes foto-térmicos para foto-irradiação específica dos lisossomas em células cancerígenas. Foram sintetizadas nanopartículas de ouro funcionalizadas com anticorpos para um direcionamento específico da membrana dos lisossomas e foram realizados ensaios de capta- ção celular e foto-termia numa linha celular de cancro colorretal. Os ensaios de captação ce- lular revelaram um aumento da captação das nanopartículas de ouro funcionalizadas com an- ticorpo e uma acumulação nos lisossomas, enquanto os estudos de viabilidade celular em re- lação aos ensaios de foto-termia não demonstraram nenhum efeito na viabilidade celular. Os resultados demonstraram uma acumulação preferencial das nanopartículas nos lisossomas, validando a sua capacidade de reconhecimento dos lisossomas. Trabalhos futuros são neces- sários para avaliar o potencial destas partículas como possíveis agentes foto-térmicos.Baptista, PedroFernandes, Maria AlexandraRUNMeireis, André Miguel Forte2023-06-02T18:06:34Z2022-122022-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/153497enginfo: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:RCAAP2024-03-11T05:36:04Zoai:run.unl.pt:10362/153497Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:55:19.654018Repositório 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 Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
title Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
spellingShingle Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
Meireis, André Miguel Forte
Cancer
Autophagy
Gold Nanoparticles
Cellular Uptake
Lysosomes
Photothermia
Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias
title_short Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
title_full Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
title_fullStr Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
title_full_unstemmed Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
title_sort Lysosomal targeting and photothermal effect of antibody functionalized gold nanoparticles in colorectal cancer cells
author Meireis, André Miguel Forte
author_facet Meireis, André Miguel Forte
author_role author
dc.contributor.none.fl_str_mv Baptista, Pedro
Fernandes, Maria Alexandra
RUN
dc.contributor.author.fl_str_mv Meireis, André Miguel Forte
dc.subject.por.fl_str_mv Cancer
Autophagy
Gold Nanoparticles
Cellular Uptake
Lysosomes
Photothermia
Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias
topic Cancer
Autophagy
Gold Nanoparticles
Cellular Uptake
Lysosomes
Photothermia
Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias
description Cancer is on the verge of becoming the number one cause of deaths worldwide, despite all the efforts and numerous studies regarding the molecular mechanisms underlying carcino- genesis and the development of new approaches to cancer therapy. Current therapies still have major downsides and to overcome them it is of high importance to develop novel approaches that offer better selectivity, minimizing the death of healthy cells, and that are able to overcome the resistance of cancer cells. Autophagy is one of the main cellular mechanisms used by cancer cells to produce enough energy for tumor development and to also resist the effects from certain therapeutic drugs. This mechanism is extremely reliant on the lysosomes and if these were to be disrupted so would the mechanism. In this work we report the study of antibody functionalized gold nanoparticles as potential photothermal agents for specific photoirradiation of the lysosomes in cancer cells. Antibody functionalized gold nanoparticles for specific targeting of the lysosomal mem- brane were synthesized, and cellular uptake and phothotermia assays were performed in a colorectal cancer cell line. Cellular uptake assays revealed increased particle uptake and lyso- somal accumulation of antibody functionalized gold nanoparticles whilst cell viability studies regarding photothermia assays showed no effect on cellular viability. Results demonstrated the active targeting of lysosomes by the synthesized nanoparticles, validating their potential as targeting agents. Future work is needed to evaluate the potential of these particles as possible photothermal agents.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
2022-12-01T00:00:00Z
2023-06-02T18:06:34Z
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dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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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
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