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Nanocápsula con transferrina para el suministro de siRNA transcelular en tejidos profundos
Ai Kohata1, P K Hashim1, Kou Okuro1
1Department of Chemistry and Biotechnology, School of Engineering , The University of Tokyo , 7-3-1 Hongo , Bunkyo-ku , Tokyo 113-8656 , Japan.
Journal of the American Chemical Society
|February 7, 2019
Resumen
Diseñamos una nanocapsula con transferrina para la administración de siRNA en el tejido profundo, lo que permite la interferencia de ARN. Este nuevo sistema logró profundidades de penetración sin precedentes en modelos de cáncer en 3D.
Área de la Ciencia:
- Biotecnología
- La nanomedicina
- Biología molecular
Sus antecedentes:
- La transferrina (Tf) facilita la transcitosis, un proceso que incluye endocitosis y exocitosis.
- La entrega eficiente de ARN pequeño interferente (siRNA) a los tejidos profundos sigue siendo un desafío para las terapias de interferencia de ARN (RNAi).
Objetivo del estudio:
- Desarrollar una nanocapsula con transferrina (TfNCsiRNA) para la administración de siRNA en el tejido profundo.
- Para lograr una interferencia efectiva del ARN (RNAi) en entornos de tejido profundo.
Principales métodos:
- Se sintetizó un nuevo macronomer (AzGu) con grupos de guanidinium, azida y tiol protegidos.
- El siRNA se complejó con AzGu, seguido de una polimerización oxidativa para formar AzNCsiRNA.
- Se utilizaron reacciones químicas y fotoquímicas para funcionalizar el nanocaplet con dendrones bioadhesivos, benzofenona y transferrina.
Principales resultados:
- Se creó la nanocápsula reactiva con siRNA más pequeña reportada hasta la fecha.
- El nanocaplet adherido a la transferrina (TfNCsiRNA) demostró una penetración profunda en el tejido, llegando a casi 70 μm en las esferoides cancerosas.
- La transcitosis inducida por Tf fue identificada como el mecanismo para la permeación de tejidos profundos.
Conclusiones:
- El sistema TfNCsiRNA desarrollado es una plataforma prometedora para la administración de ARN terapéutico en tejidos profundos.
- Esta tecnología nanocaplet supera las limitaciones anteriores para lograr una profundidad de penetración significativa para aplicaciones de RNAi.
- El estudio destaca el potencial de la transcitosis mediada por transferrina para mejorar la administración de fármacos en modelos complejos de tejidos en 3D.
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