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Transfección mediada por surfactantes gemini: escape diseñado desde el compartimiento endosómico
Paul C Bell1, Mark Bergsma, Igor P Dolbnya
1Contribution from the Physical Organic Chemistry Unit, Stratingh Institute, University of Groningen, 4 Nijenborgh, 9747 AG Groningen, The Netherlands.
Journal of the American Chemical Society
|February 6, 2003
Resumen
El tensoactivo gemini 1 a base de azúcar forma estructuras únicas de lipoplex. Un cambio inducido por el pH a una fase hexagonal invertida mejora la entrega de genes al interrumpir los endosomas para la liberación de ADN.
Área de la Ciencia:
- Química biofísica y bioquímica.
- Ciencia de los materiales Ciencia de los materiales.
- Sistemas de Entrega de Genes Sistemas de Entrega de Genes
Sus antecedentes:
- Los lipopléjicos, formados por ADN y tensioactivos catiónicos, son cruciales para la entrega de genes.
- Comprender la morfología del lipoplex es clave para optimizar la eficiencia de la transfección.
- Los tensioactivos gemini a base de azúcar ofrecen potencial para mejorar los vehículos de entrega de genes.
Objetivo del estudio:
- Para investigar los cambios estructurales del ADN / Gemini surfactante 1 lipoplexes a través de un rango de pH.
- Para correlacionar la morfología del lipoplex con la estructura del tensioactivo y la eficacia de la transfección.
- Para dilucidar el mecanismo de la liberación de genes inducida por el pH facilitado por el surfactante gemini 1.
Principales métodos:
- Diseminación de rayos X de ángulo pequeño (SAXS) para analizar las estructuras lipopléjicas.
- Microscopía cryoelectrónica (cryo-TEM) para imágenes de alta resolución de morfologías.
- Modelado molecular para vincular las características de los tensioactivos a las estructuras observadas.
Principales resultados:
- Se observaron tres morfologías distintas del lipoplejo: fase lamelar, fase lamelar condensada y fase hexagonal invertida.
- Se identificaron las principales características de los tensioactivos (longitud del espaciador, nitrógenos protonables, colas insaturadas, grupos de cabeza de azúcares) que influyen en la morfología.
- Se ha demostrado la transición inducida por el pH a la fase H (II) en el pH endosómico.
Conclusiones:
- El tensioactivo Gemini 1 forma lipoplajes sensibles al pH con morfologías sintonizables.
- La transición a una fase H (II) en el pH endosómico promueve la desestabilización endosómica y la liberación de ADN.
- Este mecanismo desencadenado por el pH explica la alta eficiencia de transfección del surfactante gemini 1 para la entrega de genes.
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