Uma equipe de pesquisadores canadenses da Université de Montréal projetou e validou uma nova classe de transportadores de drogas feitos de DNA que são 20.000 vezes menores que um cabelo humano e que podem melhorar o tratamento de câncer...
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)
O nanotransportador baseado em DNA desenvolvido por Alexis Vallée-Bélisle e sua equipe pode transportar e fornecer concentrações precisas de medicamentos: nesta foto, a doxorrubicina, um medicamento quimioterápico. Esses nanotransportadores também podem ser acoplados a biomoléculas específicas para otimizar a distribuição de medicamentos. Aqui, vemos um nanotransportador (branco) ligado à albumina (rosa) para manter a doxorrubina (azul claro) na circulação sanguínea. Crédito: Monney Medical Media / Caitlin Monney
Uma equipe de pesquisadores canadenses da Université de Montréal projetou e validou uma nova classe de transportadores de drogas feitos de DNA que são 20.000 vezes menores que um cabelo humano e que podem melhorar o tratamento de câncer e outras doenças
Relatado em um novo estudo na Nature Communications , esses transportadores moleculares podem ser programados quimicamente para fornecer a concentração ideal de medicamentos, tornando-os mais eficientes do que os métodos atuais.
Dosagem ideal em todos os momentos: um desafio médico
Uma das principais maneiras de tratar com sucesso a doença é fornecer e manter uma dosagem terapêutica do medicamento durante todo o tratamento. A exposição terapêutica abaixo do ideal reduz a eficiência e normalmente leva à resistência aos medicamentos , enquanto a superexposição aumenta os efeitos colaterais.
Manter uma concentração ótima de drogas no sangue continua sendo um grande desafio na medicina moderna. Como a maioria dos medicamentos sofre degradação rápida, os pacientes são forçados a (e muitas vezes se esquecem) de tomar doses múltiplas em intervalos regulares. E como cada paciente tem um perfil farmacocinético distinto, a concentração dos medicamentos no sangue varia significativamente.
Observando que apenas cerca de 50% dos pacientes com câncer obtêm uma dosagem ideal de medicamento durante certa quimioterapia, o professor associado de química da UdeM, Alexis Vallée-Bélisle, especialista em nanotecnologias bioinspiradas, começou a explorar como os sistemas biológicos controlam e mantêm a concentração de biomoléculas.
"Descobrimos que os organismos vivos empregam transportadores de proteínas que são programados para manter a concentração precisa de moléculas-chave, como os hormônios da tireóide , e que a força da interação entre esses transportadores e suas moléculas dita a concentração precisa da molécula livre", disse ele. .
Essa ideia simples levou Valléé-Belisle – que detém uma cadeira de pesquisa do Canadá em bioengenharia e bionanotecnologia – e sua equipe de pesquisa a começar a desenvolver transportadores artificiais de drogas que imitam o efeito natural de manter uma concentração precisa de uma droga durante o tratamento.
UdeM Ph.D. O estudante Arnaud Desrosiers, primeiro autor do estudo, inicialmente identificou e desenvolveu dois transportadores de DNA: um para a quinina, um antimalárico, e outro para a doxorrubicina, medicamento comumente usado no tratamento de câncer de mama e leucemia.
Ele então demonstrou que esses transportadores artificiais poderiam ser prontamente programados para entregar e manter qualquer concentração específica de droga.
"O mais interessante é que também descobrimos que esses nanotransportadores também podem ser empregados como reservatório de drogas para prolongar o efeito da droga e minimizar sua dosagem durante o tratamento", disse Desrosiers.
"Outra característica impressionante desses nanotransportadores", acrescentou, "é que eles podem ser direcionados para partes específicas do corpo onde a droga é mais necessária - e isso, em princípio, deve reduzir a maioria dos efeitos colaterais".
Camundongos nanotratados: cardiotoxicidade reduzida
Para demonstrar a eficácia desses nanotransportadores, os pesquisadores se uniram a Jeanne Leblond-Chain, farmacêutica da Université de Bordeaux, na França; Luc DesGroseillers, bioquímico da UdeM; Jérémie Berdugo, patologista da UdeM; Céline Fiset, farmacêutica do Montreal Heart Institute; e Vincent De Guire, bioquímico clínico do Hospital Maisonneuve-Rosemont, afiliado à UdeM.
Usando o novo transportador de drogas desenvolvido para a doxorrubicina, a equipe demonstrou que uma formulação específica do transportador de drogas permite que a doxorrubicina seja mantida no sangue e reduz drasticamente sua difusão para órgãos-chave, como coração, pulmões e pâncreas.
Nos camundongos tratados com esta formulação, a doxorrubicina foi mantida 18 vezes mais no sangue e a cardiotoxicidade também foi reduzida, mantendo os camundongos mais saudáveis, como evidenciado pelo ganho de peso normal.
"Outra grande propriedade de nossos nanotransportadores é sua alta versatilidade", disse Vallée-Bélisle.
"Por enquanto, demonstramos o princípio de funcionamento desses nanotransportadores para duas drogas diferentes. Mas graças à alta programabilidade do DNA e das proteínas químicas, agora é possível projetar esses transportadores para entregar com precisão uma ampla gama de moléculas terapêuticas".
E, acrescentou, "além disso, esses transportadores também podem ser combinados com transportadores lipossômicos projetados por humanos que agora estão sendo empregados para fornecer medicamentos em várias taxas".
Um estudo clínico para câncer de sangue?
Os pesquisadores agora estão ansiosos para validar a eficiência clínica de sua descoberta. Como o nanotransportador de doxorrubicina está programado para manter o medicamento na circulação sanguínea de maneira ideal, pode ser ideal para tratar cânceres no sangue, eles acreditam.
"Prevemos que nanotransportadores semelhantes também possam ser desenvolvidos para entregar drogas a outros locais específicos do corpo e maximizar a presença da droga em locais de tumor", disse Vallée-Bélisle. "Isso melhoraria drasticamente a eficiência dos medicamentos, bem como diminuiria seus efeitos colaterais".