Avanços recentes das abordagens nanotecnológicas para diagnóstico e tratamento do cancro colorretal
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2021
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O cancro colorretal (CCR) é o terceiro cancro mais comum do mundo e a quarta principal causa de morte associada ao cancro. A quimioterapia convencional apresenta enormes desvantagens, devido à sua baixa especificidade e aos consequentes efeitos adversos. O CCR é também uma das maiores preocupações a nível mundial devido ao seu diagnóstico invasivo e tardio. A endoscopia é a técnica de diagnóstico mais frequente e está associada a desconforto e a várias complicações, que levam o paciente a evitar este tipo de exames. Com a finalidade de melhorar o diagnóstico e a terapêutica do cancro, a nanomedicina tem suscitado interesse crescente no âmbito da oncologia. Esta área centra-se no desenvolvimento de nanoformulações direcionadas, de forma a alcançar uma terapia mais eficaz, mais segura e/ou um diagnóstico mais eficiente.
Neste contexto, esta dissertação tem como objetivo compilar os avanços recentes das abordagens nanotecnológicas para diagnóstico, tratamento e teranóstico do CCR. Para tal, foram recolhidas informações quanto a estudos pré-clínicos entre 2015-2021 e a ensaios clínicos entre 2006-2021. Por último, os resultados obtidos foram discutidos quanto ao tipo de nanopartícula mais utilizada, ao tipo de fármaco encapsulado e à estratégia de funcionalização empregue.
No geral, as nanopartículas mais exploradas para o tratamento do CCR foram as à base de lípidos e as poliméricas, enquanto as nanopartículas metálicas e de sílica foram mais exploradas para diagnóstico e teranóstico. Relativamente aos fármacos veiculados, os estudos pré-clínicos têm-se dedicado a veicular essencialmente 5-Fluorouracilo (5-FU), curcumina (CUR) e doxorrubicina (DOX), enquanto que nos ensaios clínicos, as nanoformulações veiculam maioritariamente o irinotecano (IRI), o SN-38 e a DOX. Relativamente à funcionalização das nanopartículas, a maioria dos estudos pré-clínicos foram realizados com nanossistemas sem funcionalização. Ainda assim, os ligandos mais utilizados foram: ácido fólico (AF), aptâmeros, ácido hialurónico e anticorpos.
Até ao momento, os estudos pré-clínicos e os ensaios clínicos recentes quanto à aplicação da nanomedicina no diagnóstico e na terapêutica do CCR indicam que esta é uma abordagem bastante promissora, que poderá ser uma mais-valia para ultrapassar as limitações do diagnóstico e do tratamento convencional do CCR.
Colorectal cancer (CCR) is the third most common type of cancer worldwide and is also the fourth main cause of death associated to cancer. Conventional chemotherapy has enormous disadvantages, due to the lack of specificity and the resulting adverse effects. CCR is also one of the main concerns around the world because of the invasive and late diagnosis. The usual technique for CCR diagnosis is the endoscopy, which is associated to discomfort and several complications, that leads the patients to avoid this type of exam. There has been a raising interest in nanomedicine in the field of oncology with the purpose of improving diagnosis and therapeutics of cancer. This field focuses on the development of targeting nanoformulations to develop safer and more efficacious therapies and/or more efficient diagnosis. In this context, this dissertation’s main goal is to collect the recent advances in the nanotechnological approaches for diagnosis, treatment, and theranostic of CCR. For this, information about pre-clinical studies between 2015-2021 and clinical trials between 2006-2021 were gathered. Lastly, the results obtained were discussed regarding the types of nanoparticles used, the type of encapsulated compounds used and the strategies for targeting employed. Overall, for the treatment of CCR, the nanoparticles (NPs) more explored were lipid-based and polymeric NPs and for the diagnosis and theranostic, were the metallic and silica ones. Concerning the delivery of encapsulated drugs, pre-clinical studies have been focusing on 5-flourouracil (5-FU), curcumin and doxorubicin, while clinical trials have been centred in delivering irinotecan (IRI), SN-38 and doxorubicin. Regarding the targeting of nanoparticles, the majority of pre-clinical studies report studies on nanosystems without functionalization. Nevertheless, the most used ligands were folic acid, aptamers, hyaluronic acid, and antibodies. Up to now, recent pre-clinical studies and clinical trials about the application of nanomedicine in the diagnosis and therapeutics of CCR show that this approach is very promising and may contribute to overcome the limitations of the conventional CCR diagnosis and therapeutics.
Colorectal cancer (CCR) is the third most common type of cancer worldwide and is also the fourth main cause of death associated to cancer. Conventional chemotherapy has enormous disadvantages, due to the lack of specificity and the resulting adverse effects. CCR is also one of the main concerns around the world because of the invasive and late diagnosis. The usual technique for CCR diagnosis is the endoscopy, which is associated to discomfort and several complications, that leads the patients to avoid this type of exam. There has been a raising interest in nanomedicine in the field of oncology with the purpose of improving diagnosis and therapeutics of cancer. This field focuses on the development of targeting nanoformulations to develop safer and more efficacious therapies and/or more efficient diagnosis. In this context, this dissertation’s main goal is to collect the recent advances in the nanotechnological approaches for diagnosis, treatment, and theranostic of CCR. For this, information about pre-clinical studies between 2015-2021 and clinical trials between 2006-2021 were gathered. Lastly, the results obtained were discussed regarding the types of nanoparticles used, the type of encapsulated compounds used and the strategies for targeting employed. Overall, for the treatment of CCR, the nanoparticles (NPs) more explored were lipid-based and polymeric NPs and for the diagnosis and theranostic, were the metallic and silica ones. Concerning the delivery of encapsulated drugs, pre-clinical studies have been focusing on 5-flourouracil (5-FU), curcumin and doxorubicin, while clinical trials have been centred in delivering irinotecan (IRI), SN-38 and doxorubicin. Regarding the targeting of nanoparticles, the majority of pre-clinical studies report studies on nanosystems without functionalization. Nevertheless, the most used ligands were folic acid, aptamers, hyaluronic acid, and antibodies. Up to now, recent pre-clinical studies and clinical trials about the application of nanomedicine in the diagnosis and therapeutics of CCR show that this approach is very promising and may contribute to overcome the limitations of the conventional CCR diagnosis and therapeutics.
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Orientação: Catarina Pereira Leite
Palavras-chave
MESTRADO INTEGRADO EM CIÊNCIAS FARMACÊUTICAS, CIÊNCIAS FARMACÊUTICAS, CANCRO COLORRETAL, NANOPARTÍCULAS, TRATAMENTOS FARMACOLÓGICOS, PHARMACEUTICAL SCIENCES, COLORECTAL CANCER, NANOPARTICLES, PHARMACOLOGICAL TREATMENTS, DIAGNOSES, DIAGNÓSTICOS, NANOMEDICINA TERANÓSTICA, THERANOSTIC NANOMEDICINE