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Nanomedicina: aplicação de anticorpos monoclonais em nanossistemas na terapêutica de cancro colorretal
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Abstract(s)
O cancro colorretal (CCR) é um cancro que se desenvolve no intestino grosso, mais especificamente no cólon que é a parte mais comprida ou no reto, que é a parte final mais reta do intestino grosso. O CCR é o 3º cancro mais comum a seguir ao cancro da mama e da próstata, com uma taxa de incidência acima dos 30 casos por 100.000 habitantes em Portugal, afetando mais os homens do que as mulheres, tendo sido diagnosticados mais de 1,3 milhões de novos casos em 2012. O risco de desenvolver CCR é multifatorial, estando associado a fatores como o tabagismo, a obesidade, a inatividade física, o consumo elevado de carne vermelha, os fatores genéticos e sendo a idade o maior fator de risco.
A quimioterapia convencional, muitas vezes não consegue eliminar subpopulações de células cancerígenas altamente agressivas e dotadas de resistência à quimioterapia, as quais possuem a capacidade de melhorar a heterogeneidade do tumor e desenvolver metástases. Uma das abordagens para contornar estes problemas é a utilização de anticorpos monoclonais, sendo que este conceito foi proposto por Paul Ehrlich há mais de um século. O desenvolvimento da tecnologia de hibridomas em 1975 permitiu a produção de anticorpos monoclonais. Juntamente com a sua especificidade para o alvo, sendo relativamente bem tolerados e apresentando uma semi-vida longa, contribuíram para o sucesso no desenvolvimento de medicamentos. Os anticorpos monoclonais melhoram significativamente o tratamento de uma variedade de doenças humanas. Os mecanismos de ação mais bem descritos de anticorpos monoclonais terapêuticos incluem citotoxicidade mediada por células dependente de anticorpos, citotoxicidade dependente do complemento, fagocitose celular dependente de anticorpos e indução da morte celular.
De forma a melhorar a adesão à terapêutica e aumentar mais a especificidade é cada vez mais comum associar anticorpos monoclonais à nanomedicina. A nanomedicina tem vindo a desenvolver-se em grande escala nos últimos anos, nas áreas de terapêutica, diagnóstico e biossensores, agentes de imagem e monitorização e reparação e engenharia tecidular. As várias aplicações indicam, que a associação de anticorpos monoclonais à nanotecnologia melhora significativamente os resultados terapêuticos, pois os anticorpos têm elevada especificidade com efeitos secundários mais reduzidos e são o foco de muitos trabalhos de investigação em doenças que necessitam de tratamento clínico ou cirúrgico intensivo.
O objetivo desta monografia é explorar a utilização de anticorpos monoclonais em nanotecnologia no tratamento do cancro colorretal, abordando-se os diferentes nanossistemas existentes e as suas potenciais vantagens, como forma de aumentar a especificidade para o CCR.
Colorectal cancer (CRC) develops in the large intestine, more specifically in the colon, which is the longest part of in the rectum, which is the straightest end of the large intestine. CRC is the 3rd most common cancer after breast and prostate cancer, with an incidence rate above 30 cases per 100,000 inhabitants in Portugal, affecting men more than women. Around 1.3 million of new cases were diagnosed in 2012. The risk of developing CRC is multifactorial, being associated with factors such as smoking, obesity, physical inactivity, high consumption of red meat, genetic factors and with age being the biggest risk factor. Conventional chemotherapy often fails to eliminate subpopulations of highly aggressive cancer cells that are resistant to chemotherapy, can improve tumor heterogeneity, develop metastasis and lack specificity. One of the approaches to solve these problems is the use of monoclonal antibodies, and this concept was proposed by Paul Ehrlich more than a century ago. The development of hybridoma technology in 1975 allowed the production of monoclonal antibodies. Together with its specificity for the target, being relatively well tolerated and presenting a long half-life, they contributed to the success in the development of medicines. Monoclonal antibodies significantly improve the treatment of a variety of human diseases. The best-described mechanisms of action of therapeutic monoclonal antibodies include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cell phagocytosis, and apoptosis. To improve adherence to therapy and increase the specificity even more, it is increasingly common to associate monoclonal antibodies to nanomedicine. Nanomedicine has been developing on a large scale in recent years, not only in the therapeutic area, where there are applications by various routes of administration (ex: topical, oral, parenteral, pulmonary, etc.), but also in diagnostic and biosensors, imaging and monitoring agents and tissue repair and engineering. This proves that nanotechnology associated with monoclonal antibodies significantly improves therapeutic results, as they have high specificity with reduced side effects and are the focus of many studies on diseases that need intensive clinical or surgical treatment. The objective of this work is to explore the use of monoclonal antibodies in nanotechnology in the treatment of CRC, addressing the different existing nanosystems and their potential advantages, as a way of increasing the specificity for CRC.
Colorectal cancer (CRC) develops in the large intestine, more specifically in the colon, which is the longest part of in the rectum, which is the straightest end of the large intestine. CRC is the 3rd most common cancer after breast and prostate cancer, with an incidence rate above 30 cases per 100,000 inhabitants in Portugal, affecting men more than women. Around 1.3 million of new cases were diagnosed in 2012. The risk of developing CRC is multifactorial, being associated with factors such as smoking, obesity, physical inactivity, high consumption of red meat, genetic factors and with age being the biggest risk factor. Conventional chemotherapy often fails to eliminate subpopulations of highly aggressive cancer cells that are resistant to chemotherapy, can improve tumor heterogeneity, develop metastasis and lack specificity. One of the approaches to solve these problems is the use of monoclonal antibodies, and this concept was proposed by Paul Ehrlich more than a century ago. The development of hybridoma technology in 1975 allowed the production of monoclonal antibodies. Together with its specificity for the target, being relatively well tolerated and presenting a long half-life, they contributed to the success in the development of medicines. Monoclonal antibodies significantly improve the treatment of a variety of human diseases. The best-described mechanisms of action of therapeutic monoclonal antibodies include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cell phagocytosis, and apoptosis. To improve adherence to therapy and increase the specificity even more, it is increasingly common to associate monoclonal antibodies to nanomedicine. Nanomedicine has been developing on a large scale in recent years, not only in the therapeutic area, where there are applications by various routes of administration (ex: topical, oral, parenteral, pulmonary, etc.), but also in diagnostic and biosensors, imaging and monitoring agents and tissue repair and engineering. This proves that nanotechnology associated with monoclonal antibodies significantly improves therapeutic results, as they have high specificity with reduced side effects and are the focus of many studies on diseases that need intensive clinical or surgical treatment. The objective of this work is to explore the use of monoclonal antibodies in nanotechnology in the treatment of CRC, addressing the different existing nanosystems and their potential advantages, as a way of increasing the specificity for CRC.
Description
Keywords
Anticorpos monoclonais Cancro colorretal Nanomedicina Nanossistemas e nanotecnologia