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Las nanoestructuras autoensambladas regulan la liberación de H2S de péptidos constitucionalmente isoméricos
Yin Wang1, Kuljeet Kaur1, Samantha J Scannelli1
1Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute , Virginia Tech , Blacksburg , Virginia 24061 , United States.
Journal of the American Chemical Society
|October 30, 2018
Resumen
Los investigadores desarrollaron conjugados donantes de péptido-sulfuro de hidrógeno (H2S) que se autoensamblan en diferentes nanoestructuras. La nanocola PHDC demostró una mitigación superior de la cardiotoxicidad de la doxorrubicina, mostrando relaciones estructura-función en los biomateriales que liberan H2S.
Área de la Ciencia:
- Ciencia de los biomateriales
- Química supramolecular
- Química medicinal
Sus antecedentes:
- El sulfuro de hidrógeno (H2S) es un gas de señalización biológica con potencial terapéutico.
- El desarrollo de sistemas controlados de suministro de H2S es crucial para las aplicaciones terapéuticas.
- El autoensamblaje de péptidos ofrece una plataforma para crear nanomateriales funcionales.
Objetivo del estudio:
- Para sintetizar y caracterizar los conjugados donantes de péptido-sulfuro de hidrógeno (PHDC).
- Para investigar el comportamiento de autoensamblaje y la cinética de liberación de H2S de los PHDC.
- Evaluar la eficacia terapéutica de los PHDC para mitigar la cardiotoxicidad inducida por la doxorrubicina.
Principales métodos:
- Síntesis de tres PHDC constitucionalmente isoméricos que contienen residuos de ácido glutámico y lisina funcionalizados con S-aroiltiooximas (SATO).
- Caracterización del autoensamblaje de PHDC en diferentes morfologías (nanoribones y nanobobinas) en solución acuosa.
- Evaluación de las tasas de liberación de H2S y su dependencia de la morfología y la descomposición SATO.
- Evaluación in vitro de la mitigación de la cardiotoxicidad de la doxorrubicina por diferentes morfologías de PHDC.
Principales resultados:
- Los PHDC se autoensamblan en nanoestructuras distintas: dos nanocintas y una nanobobina.
- Las tasas de liberación de H2S variaron con la morfología; la nano bobina exhibió cinética de liberación compleja.
- El PHDC formador de nano bobinas mitigó significativamente la cardiotoxicidad de la doxorrubicina, superando el rendimiento de los isómeros de nano cinta y los donantes convencionales de H2S.
Conclusiones:
- Los PHDC pueden diseñarse para autoensamblarse en diversas nanoestructuras con liberación ajustable de H2S.
- La morfología juega un papel crítico en el perfil de liberación de H2S y la eficacia terapéutica de los PHDC.
- Este estudio presenta una nueva estrategia para desarrollar biomateriales avanzados que liberan H2S con aplicaciones terapéuticas potenciales.
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