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Enzyme-boosted IONzymes for cancer theranostics
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O cancro é uma das principais causas de morte a nível mundial. Terapias convencionais tais como cirurgia, radio- e quimioterapia estão normalmente associadas a uma resposta parcial, breve e imprevisível do tumor. Assim, existe uma necessidade de melhorar a qualidade e especificidade dos tratamentos. O teranóstico de cancro é uma nova abordagem que combina diagnóstico e terapêutica com o objetivo de diminuir os atrasos nos tratamentos, melhorar a assistência ao paciente, e personalizar as abordagens. Assim, uma das plataformas mais usadas são as nanopartículas superparamagnéticas de óxido de ferro (SPIONs). Estas podem ser usadas como agentes de contraste em imagem por ressonância magnética e em hipertermia magnética devido ao aumento de temperatura nos arredores do tecido tumoral, quando um campo magnético alternado é aplicado. Além das propriedades já conhecidas das SPIONs, foi descoberto que estas nanopartículas conseguem mimetizar enzimas tais como a peroxidase e a catalase. A última converte peróxido de hidrogénio em água e oxigénio, ajudando a reverter a hipoxia presente nos tecidos tumorais. Outra forma de reforçar a atividade de catalase e, consequentemente, melhorar os resultados de hipertermia é funcionalizar as SPIONs com a enzima catalase para ultrapassar a hipoxia in situ.
As nanopartículas foram revestidas com ácido dimercaptosuccínico (DMSA) e 3-amino-propil-trietoxissilano (APTES) e amplamente caracterizadas. A atividade enzimática das nanopartículas revestidas também foi avaliada. Após esta caracterização, a catalase foi imobilizada na superfície das nanopartículas. Os complexos de imobilização foram submetidos a testes de hipertermia magnética e as variações de temperatura sob a aplicação de campo magnético alternado mostraram ser possíveis de atingir temperaturas hipertérmicas. Por fim, foi avaliada a citotoxicidade dos complexos nas linhas celulares Vero e SaOs-2, sendo o complexo de imobilização usando glutaraldeído o menos citotóxico para ambas linhas celulares. Consequentemente, as propriedades das nanopartículas magnéticas produzidas são consideradas indicadas para o seu uso como plataforma no teranóstico de cancro.
Cancer is one of the leading causes of death worldwide. Conventional therapies such as surgery, radio- and chemotherapy are usually associated with the partial, brief, and unpredictable tumor response. Thus, there is an urge to improve the quality and specificity of treatments. Cancer theranostics is a new approach that combines diagnosis and therapeutics to decrease treatment delays, improve patient care, and personalize cancer approaches. Therefore, one of the most common platforms used is superparamagnetic oxide nanoparticles (SPIONs). These can be used as a contrast agent in Magnetic Resonance Imaging and in magnetic hyperthermia due to the increase of their bulk temperature and the surroundings when an alternating magnetic field is applied. Along with the so-known properties of SPIONs, these nanoparticles can mimic enzymes such as peroxidase and catalase. The latter converts hydrogen peroxide into water and oxygen, helping overcome the hypoxia present in tumor tissues. Another way to boost catalase activity and consequently improve hyperthermia outcomes is to functionalize SPIONs with the enzyme catalase to overcome hypoxia in situ. Nanoparticles were coated with dimercaptosuccinic acid (DMSA) and 3-amino-propyltriethoxysilane (APTES) and extensively characterized. The enzyme-like activity of peroxidase and catalase of coated nanoparticles was also evaluated. After this characterization, catalase was immobilized onto the nanoparticles surface. The immobilization complexes were submitted to magnetic hyperthermia and the temperature variations under the application of an alternating magnetic field showed to be possible to reach hyperthermic temperatures. Finally, the complexes’ cytotoxicity in Vero and SaOs-2 cell lines was assessed, being the immobilization complex using glutaraldehyde less cytotoxic for both cell lines. Consequently, the properties of the produced magnetic nanoparticles are considered to represent them as a platform for application in cancer therapy and diagnostics.
Cancer is one of the leading causes of death worldwide. Conventional therapies such as surgery, radio- and chemotherapy are usually associated with the partial, brief, and unpredictable tumor response. Thus, there is an urge to improve the quality and specificity of treatments. Cancer theranostics is a new approach that combines diagnosis and therapeutics to decrease treatment delays, improve patient care, and personalize cancer approaches. Therefore, one of the most common platforms used is superparamagnetic oxide nanoparticles (SPIONs). These can be used as a contrast agent in Magnetic Resonance Imaging and in magnetic hyperthermia due to the increase of their bulk temperature and the surroundings when an alternating magnetic field is applied. Along with the so-known properties of SPIONs, these nanoparticles can mimic enzymes such as peroxidase and catalase. The latter converts hydrogen peroxide into water and oxygen, helping overcome the hypoxia present in tumor tissues. Another way to boost catalase activity and consequently improve hyperthermia outcomes is to functionalize SPIONs with the enzyme catalase to overcome hypoxia in situ. Nanoparticles were coated with dimercaptosuccinic acid (DMSA) and 3-amino-propyltriethoxysilane (APTES) and extensively characterized. The enzyme-like activity of peroxidase and catalase of coated nanoparticles was also evaluated. After this characterization, catalase was immobilized onto the nanoparticles surface. The immobilization complexes were submitted to magnetic hyperthermia and the temperature variations under the application of an alternating magnetic field showed to be possible to reach hyperthermic temperatures. Finally, the complexes’ cytotoxicity in Vero and SaOs-2 cell lines was assessed, being the immobilization complex using glutaraldehyde less cytotoxic for both cell lines. Consequently, the properties of the produced magnetic nanoparticles are considered to represent them as a platform for application in cancer therapy and diagnostics.
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Cancer Catalase Iron oxide nanoparticles IONzymes Magnetic hyperthermia Theranostic