Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer

Detalhes bibliográficos
Autor(a) principal: Leite, João Maria Silva Pinto
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10773/30892
Resumo: Biopolymeric nanobeads stand out as being biocompatible, biodegradable, and chemically versatile nanomaterials for several biomedical applications. In this context, cellulose has shown an increasing potential in this field due to its abundance of hydroxyl groups and consequent ability to be functionalized. Therefore, the objective of the present dissertation consists in the preparation and characterization of multifunctional cellulose-based nanobeads for potential application in cancer diagnosis and treatment. Spherical cellulose-based nanobeads were produced by nanoprecipitation and functionalized with gold nanoparticles (AuNPs) that will play the dual role of cell imaging and therapeutic agent. The cellulose nanobeads were prepared using cellulose acetate (CA) as the starting raw material instead of directly using cellulose because of its high insolubility in most common solvents. So, CA nanobeads were obtained by nanoprecipitation through CA dissolution and regeneration, followed by alkaline hydrolysis to obtain the cellulose nanobeads. Subsequently, cellulose nanobeads/AuNPs hybrid systems were developed by two distinct methodologies, namely by CA regeneration in the presence of AuNPs and subsequent alkaline hydrolysis, or by the in situ reduction of the gold salt in the presence of the cellulose nanobeads. The cellulose nanobeads/AuNPs hybrids were then characterized by scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, and ultraviolet-visible spectroscopy (UV-vis). Overall, the production of the cellulose nanobeads was achieved by dissolving CA in acetone and subsequent regeneration using water as the non-solvent, followed by alkaline hydrolysis. The success of the hydrolysis was confirmed by ATR-FTIR spectroscopy and SEM, while the synthesis of AuNPs was corroborated by UV-vis spectroscopy and STEM. The morphology and size of the hybrid systems were evaluated by SEM and STEM, which confirmed the production of the cellulose nanobeads/AuNPs hybrids with an average size of 415±187 nm for the cellulose nanobeads and 15±3 nm for the AuNPs. Moreover, the in vitro cytotoxicity of the cellulose nanobeads/AuNPs hybrids towards the pigmented human melanoma (MNT-1) cell line was evaluated for 24 h. The resultant data showed that the hybrid system exhibits a dose dependent cellular toxicity, reaching 81.6±4.5% of cell viability for 39.0 μg mL–1 of hybrid system. Thus, a higher dose will most definitely translate into a higher cytotoxic effect towards the tumor cells. All the obtained results revealed that the cellulose nanobeads/AuNPs hybrids have potential for application in the diagnosis and therapy of cancer.
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spelling Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancerCellulose acetateNanoprecipitationFunctional cellulose nanobeadsGold nanoparticlesCancer therapy and diagnosticsBiopolymeric nanobeads stand out as being biocompatible, biodegradable, and chemically versatile nanomaterials for several biomedical applications. In this context, cellulose has shown an increasing potential in this field due to its abundance of hydroxyl groups and consequent ability to be functionalized. Therefore, the objective of the present dissertation consists in the preparation and characterization of multifunctional cellulose-based nanobeads for potential application in cancer diagnosis and treatment. Spherical cellulose-based nanobeads were produced by nanoprecipitation and functionalized with gold nanoparticles (AuNPs) that will play the dual role of cell imaging and therapeutic agent. The cellulose nanobeads were prepared using cellulose acetate (CA) as the starting raw material instead of directly using cellulose because of its high insolubility in most common solvents. So, CA nanobeads were obtained by nanoprecipitation through CA dissolution and regeneration, followed by alkaline hydrolysis to obtain the cellulose nanobeads. Subsequently, cellulose nanobeads/AuNPs hybrid systems were developed by two distinct methodologies, namely by CA regeneration in the presence of AuNPs and subsequent alkaline hydrolysis, or by the in situ reduction of the gold salt in the presence of the cellulose nanobeads. The cellulose nanobeads/AuNPs hybrids were then characterized by scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, and ultraviolet-visible spectroscopy (UV-vis). Overall, the production of the cellulose nanobeads was achieved by dissolving CA in acetone and subsequent regeneration using water as the non-solvent, followed by alkaline hydrolysis. The success of the hydrolysis was confirmed by ATR-FTIR spectroscopy and SEM, while the synthesis of AuNPs was corroborated by UV-vis spectroscopy and STEM. The morphology and size of the hybrid systems were evaluated by SEM and STEM, which confirmed the production of the cellulose nanobeads/AuNPs hybrids with an average size of 415±187 nm for the cellulose nanobeads and 15±3 nm for the AuNPs. Moreover, the in vitro cytotoxicity of the cellulose nanobeads/AuNPs hybrids towards the pigmented human melanoma (MNT-1) cell line was evaluated for 24 h. The resultant data showed that the hybrid system exhibits a dose dependent cellular toxicity, reaching 81.6±4.5% of cell viability for 39.0 μg mL–1 of hybrid system. Thus, a higher dose will most definitely translate into a higher cytotoxic effect towards the tumor cells. All the obtained results revealed that the cellulose nanobeads/AuNPs hybrids have potential for application in the diagnosis and therapy of cancer.Nanobeads biopoliméricas destacam-se como sendo nanomateriais biocompatíveis, biodegradáveis e quimicamente versáteis para diversas aplicações biomédicas. Neste âmbito, a celulose tem demonstrado um potencial crescente para estas aplicações devido à sua abundância de grupos hidroxilo e consequente aptidão para ser funcionalizada. Neste contexto, o objetivo da presente dissertação consiste na preparação e caracterização de nanobeads multifuncionais à base de celulose para potencial aplicação no diagnóstico e tratamento do cancro. Nanobeads esféricas à base de celulose foram produzidas por nanoprecipitação e funcionalizadas com nanopartículas de ouro (AuNPs) que podem desempenhar um papel duplo como agente de contraste para imagiologia e agente terapêutico. As nanobeads de celulose foram preparadas usando acetato de celulose (CA) como matéria-prima inicial em vez de usar diretamente a celulose devido à sua insolubilidade na maioria dos solventes convencionais. Deste modo, as nanobeads de CA foram obtidas por nanoprecipitação através da dissolução e regeneração do CA, seguida de uma hidrólise alcalina para a obtenção das nanobeads de celulose. Posteriormente, desenvolveram-se sistemas híbridos de nanobeads de celulose/AuNPs seguindo duas metodologias distintas, nomeadamente, por regeneração de CA na presença de AuNPs e subsequente hidrólise alcalina, ou pela redução in situ do sal de ouro na presença das nanobeads de celulose. Os sistemas híbridos foram posteriormente caracterizados por microscopia eletrónica de varrimento (SEM), microscopia eletrónica de varrimento em modo de transmissão (STEM), espectroscopia de infravermelho com reflexão total atenuada e transformada de Fourier (ATR-FTIR), e espectroscopia de ultravioleta-visível (UV-vis). Em suma, a produção de nanobeads de celulose foi conseguida dissolvendo o CA em acetona e subsequente regeneração usando água como o anti solvente, seguida de hidrólise alcalina. O sucesso da hidrólise foi comprovado por espectroscopia de ATR-FTIR e SEM, enquanto que a síntese das AuNPs foi confirmada por espectroscopia de UV-vis e STEM. A morfologia e o tamanho dos sistemas híbridos foram avaliados por SEM e STEM, os quais confirmaram a produção de sistemas híbridos de nanobeads de celulose/AuNPs com tamanho médio de 415±187 nm para as nanobeads de celulose e 15±3 nm para as AuNPs. Adicionalmente, a citotoxicidade in vitro dos sistemas híbridos foi avaliada em células humanas pigmentadas de melanoma (MNT-1) ao fim de 24 h. Os resultados mostraram que o sistema híbrido possui uma toxicidade celular dependente da concentração, alcançando 81.6±4.5% de viabilidade celular para 39.0 μg mL–1 do híbrido. Deste modo, uma concentração mais elevada promoverá uma maior resposta citotóxica nas células cancerígenas. Todos os resultados obtidos evidenciam o potencial dos sistemas híbridos de nanobeads de celulose/AuNPs para aplicação no diagnóstico e terapia do cancro.2023-03-03T00:00:00Z2021-02-22T00:00:00Z2021-02-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/30892engLeite, João Maria Silva Pintoinfo:eu-repo/semantics/embargoedAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-06T04:30:54Zoai:ria.ua.pt:10773/30892Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T14:11:12.977926Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
title Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
spellingShingle Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
Leite, João Maria Silva Pinto
Cellulose acetate
Nanoprecipitation
Functional cellulose nanobeads
Gold nanoparticles
Cancer therapy and diagnostics
title_short Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
title_full Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
title_fullStr Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
title_full_unstemmed Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
title_sort Multifunctional cellulose nanoparticles for potential application on the diagnosis and treatment of cancer
author Leite, João Maria Silva Pinto
author_facet Leite, João Maria Silva Pinto
author_role author
dc.contributor.author.fl_str_mv Leite, João Maria Silva Pinto
dc.subject.por.fl_str_mv Cellulose acetate
Nanoprecipitation
Functional cellulose nanobeads
Gold nanoparticles
Cancer therapy and diagnostics
topic Cellulose acetate
Nanoprecipitation
Functional cellulose nanobeads
Gold nanoparticles
Cancer therapy and diagnostics
description Biopolymeric nanobeads stand out as being biocompatible, biodegradable, and chemically versatile nanomaterials for several biomedical applications. In this context, cellulose has shown an increasing potential in this field due to its abundance of hydroxyl groups and consequent ability to be functionalized. Therefore, the objective of the present dissertation consists in the preparation and characterization of multifunctional cellulose-based nanobeads for potential application in cancer diagnosis and treatment. Spherical cellulose-based nanobeads were produced by nanoprecipitation and functionalized with gold nanoparticles (AuNPs) that will play the dual role of cell imaging and therapeutic agent. The cellulose nanobeads were prepared using cellulose acetate (CA) as the starting raw material instead of directly using cellulose because of its high insolubility in most common solvents. So, CA nanobeads were obtained by nanoprecipitation through CA dissolution and regeneration, followed by alkaline hydrolysis to obtain the cellulose nanobeads. Subsequently, cellulose nanobeads/AuNPs hybrid systems were developed by two distinct methodologies, namely by CA regeneration in the presence of AuNPs and subsequent alkaline hydrolysis, or by the in situ reduction of the gold salt in the presence of the cellulose nanobeads. The cellulose nanobeads/AuNPs hybrids were then characterized by scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, and ultraviolet-visible spectroscopy (UV-vis). Overall, the production of the cellulose nanobeads was achieved by dissolving CA in acetone and subsequent regeneration using water as the non-solvent, followed by alkaline hydrolysis. The success of the hydrolysis was confirmed by ATR-FTIR spectroscopy and SEM, while the synthesis of AuNPs was corroborated by UV-vis spectroscopy and STEM. The morphology and size of the hybrid systems were evaluated by SEM and STEM, which confirmed the production of the cellulose nanobeads/AuNPs hybrids with an average size of 415±187 nm for the cellulose nanobeads and 15±3 nm for the AuNPs. Moreover, the in vitro cytotoxicity of the cellulose nanobeads/AuNPs hybrids towards the pigmented human melanoma (MNT-1) cell line was evaluated for 24 h. The resultant data showed that the hybrid system exhibits a dose dependent cellular toxicity, reaching 81.6±4.5% of cell viability for 39.0 μg mL–1 of hybrid system. Thus, a higher dose will most definitely translate into a higher cytotoxic effect towards the tumor cells. All the obtained results revealed that the cellulose nanobeads/AuNPs hybrids have potential for application in the diagnosis and therapy of cancer.
publishDate 2021
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2021-02-22
2023-03-03T00:00:00Z
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