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Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
Published on: November 21, 2013
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El pH y la estructura anfifílica dirigen el comportamiento supramolecular en conjuntos biofuncionales.
Tyson J Moyer1, Joel A Finbloom, Feng Chen
1Institute for BioNanotechnology in Medicine and ∥Department of Medicine, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
Journal of the American Chemical Society
|October 14, 2014
Resumen
Los investigadores diseñaron péptidos anfífilos sensibles al pH que se autoensamblan en nanofibras o esferas. Estas nanoestructuras cambian de forma en ambientes tumorales ácidos, mejorando la encapsulación de fármacos y la administración para la nanomedicina del cáncer.
Área de la Ciencia:
- Se trata de una química supramolecular.
- Ciencia de los materiales ciencia de los materiales.
- Nanotecnología La nanotecnología es la nanotecnología.
Sus antecedentes:
- El autoensamblaje supramolecular permite el control de la morfología de la nanoestructura y la respuesta a los estímulos.
- El desarrollo de sistemas de respuesta a estímulos es crucial para la administración de fármacos dirigidos.
Objetivo del estudio:
- Diseñar péptidos anfífilos sensibles al pH (PAs) que controlen la forma de la nanoestructura en respuesta a los microambientes tumorales.
- Evaluar el impacto de las transiciones morfológicas inducidas por el pH en la encapsulación de fármacos y la acumulación de tumores.
Principales métodos:
- Sintetizó dos péptidos anfífilos (PAs) que incorporan una secuencia H6 de oligo-histidina.
- Autoensamblaje investigado en nanofibras o micelas esféricas basadas en la colocación alifática de la cola.
- Desmontaje evaluado dependiente del pH y cambios morfológicos reversibles entre pH 6.0 y 6.5.
- Evaluación de la eficiencia de encapsulación de la camptotecina (CPT) en diferentes nanoestructuras.
- Acumulación tumoral cuantificada de nanofibras sensibles al pH en comparación con los controles.
Principales resultados:
- Los PAs formaron morfologías distintas a nanoescala (nanofibras o micelas esféricas) controladas por la posición alifática de la cola.
- Ambos tipos de PA exhibieron desmontaje reversible en condiciones ácidas (pH 6.0-6.5) debido a la protonación de histidina.
- Las nanofibras basadas en H6 lograron hasta un 60% de eficiencia de encapsulación de camptotecina, un aumento de siete veces en comparación con las micelas esféricas.
- Las nanofibras sensibles al pH demostraron una mayor acumulación de tumores en comparación con las micelas esféricas y las nanofibras que no cambian la morfología.
Conclusiones:
- Las transiciones morfológicas de las nanoestructuras supramoleculares provocadas por cambios en el pH impactan significativamente en la encapsulación de fármacos y la acumulación de tumores.
- El diseño molecular del autoensamblaje supramolecular se puede ajustar para mejorar las propiedades farmacológicas de los nanomedicamentos.
- Los péptidos anfífilos sensibles al pH ofrecen una plataforma prometedora para el desarrollo de nanoterapéuticas de cáncer avanzado.
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