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Desarrollo de una nanoplataforma controlada por luz para la entrega nuclear directa de materiales moleculares y a
Ya-Xuan Zhu1, Hao-Ran Jia1, Guang-Yu Pan1
1State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering , Southeast University , 2 Sipailou Road , Nanjing 210096 , P. R. China.
Journal of the American Chemical Society
|February 7, 2018
Resumen
Los investigadores desarrollaron una nueva nanoplataforma utilizando silsesquioxano oligomérico poliédrico (POSS), polietilenglicol (PEG) y rosa bengal (RB) para la administración nuclear controlada por luz de fármacos y nanomateriales.
Área de la Ciencia:
- Ingeniería biomédica
- Nanotecnología
- Biología celular
Sus antecedentes:
- La membrana nuclear es una barrera significativa para los agentes dirigidos al núcleo debido al tamaño limitado de los poros nucleares (9-12 nm).
- La entrega nuclear efectiva es crucial para varias aplicaciones, incluida la quimioterapia y la nanomedicina.
Objetivo del estudio:
- Desarrollar una plataforma general y controlable para suministrar compuestos químicos y nanomateriales a los núcleos celulares.
- Para superar la barrera de la membrana nuclear usando un mecanismo inducible por la luz.
Principales métodos:
- Autoensamblaje de POSS, PEG y rose bengal (RB) que contienen poliaminas en nanopartículas (PPR NP).
- Utilizando la generación de oxígeno singlete inducida por la luz para interrumpir los lisosomas y facilitar la penetración de la membrana nuclear.
- Carga de agentes quimioterapéuticos y nanomateriales en PPR NPs para su administración.
Principales resultados:
- Las PPR NPs se internalizaron en las células y se localizaron en los lisosomas.
- La irradiación de luz leve desencadenó la producción de oxígeno singlete, interrumpiendo los lisosomas y haciendo que los PPR NP se acumulen en la membrana nuclear.
- Se logró una entrega nuclear exitosa controlada por luz de agentes quimioterapéuticos (10-hidroxicamptotecina, docetaxel), un tinte fluorescente (DiD) y nanomateriales (NPs azules prusianos, nanorods de oro).
- La nanoplataforma demostró aplicabilidad general y evitó modificaciones complejas del ligando.
Conclusiones:
- La plataforma PPR NP desarrollada ofrece un enfoque altamente controlable y general para la entrega nuclear.
- Esta estrategia activada por la luz evita efectivamente la barrera de la membrana nuclear tanto para las cargas útiles moleculares como para los nanomateriales.
- La nanoplataforma presenta una alternativa prometedora a los métodos tradicionales de administración nuclear, mejorando el potencial terapéutico y diagnóstico.
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