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Polímeros PEG-branch-azide bivalentes-botella-escobilla clictables en el núcleo por ROMP: injerto-a través y
Jeremiah A Johnson1, Ying Y Lu, Alan O Burts
1Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.
Journal of the American Chemical Society
|December 15, 2010
Resumen
Los investigadores crearon nuevas nanoestructuras ramificadas utilizando la química del clic. Estas estructuras entregan de manera eficiente el fármaco contra el cáncer doxorubicina (DOX) a las células, lo que demuestra la eficacia terapéutica después de la activación de la luz UV.
Área de la Ciencia:
- Química de Polímeros La Química de Polímeros es la química de los polímeros.
- Nanotecnología La nanotecnología es la nanotecnología.
- Entrega de drogas Envío de drogas
Sus antecedentes:
- La química de clic y las polimerizaciones eficientes permiten la síntesis de nuevas nanoestructuras.
- Desarrollar nanocarriers diseñados con precisión es crucial para la administración de fármacos dirigidos.
- Los métodos anteriores carecían de una síntesis fácil de nanoestructuras ramificadas con capacidades de conjugación de fármacos.
Objetivo del estudio:
- Para sintetizar una nueva clase de nanoestructuras ramificadas que se pueden hacer clic: polímeros de polietileno glicol (PEG) - ramificación-azida bivalente-escobillo.
- Para funcionalizar estas nanoestructuras con doxorubicina (DOX) a través de la química de clics.
- Para evaluar la eficacia terapéutica de las nanoestructuras cargadas de DOX.
Principales métodos:
- La polimerización de la metátesis de apertura de anillo a través del injerto de un macronomer de cloruro de norborneo-PEG.
- Intercambio de halidas-azidas para introducir grupos azidas.
- Cicloadición azida-alquina catalizada por cobre (CuAAC) para la conjugación DOX.
- Fotólisis UV para la liberación de fármacos y estudios in vitro de células cancerosas.
Principales resultados:
- Fácil síntesis de polímeros de cepillado bivalentes de PEG-branch-azide que se asemejan a micelas unimoleculares.
- Acoplamiento CuAAC cuantitativo de un derivado de DOX-alquino fotocleable al núcleo de azida a través de varios tamaños nanoscópicos (6-50 nm).
- Liberación inducida por UV de DOX activo de las nanoestructuras, mostrando eficacia terapéutica contra las células cancerosas humanas.
Conclusiones:
- Los polímeros bivalentes desarrollados sirven como plataformas versátiles para la síntesis de nanoestructuras y la conjugación de fármacos.
- El enfoque de la química del clic permite una carga de fármacos eficiente e independiente del tamaño.
- Estas nanoestructuras demuestran un potencial significativo para la terapia dirigida contra el cáncer con liberación de fármacos desencadenada por la luz.
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