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Monitoreo in situ del proceso de apoptosis mediante un fotosensibilizador automático

Tianfu Zhang¹, Yuanyuan Li¹, Zheng Zheng¹

¹Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemical and Biological Engineering , The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon , Hong Kong , China.

Journal of the American Chemical Society

|March 29, 2019

Resumen

Un nuevo fotosensibilizador autoinformativo (PS) permite el monitoreo en tiempo real de la terapia fotodinámica (PDT) mediante el seguimiento de su migración de fluorescencia. Esto permite un control preciso de la dosis, minimizando los efectos secundarios y mejorando los resultados del tratamiento.

Área de la Ciencia:

Ingeniería biomédica
La fotoquímica
Imágenes moleculares

Sus antecedentes:

La terapia fotodinámica (PDT) es un tratamiento prometedor para el cáncer.
La sobredosis de PDT puede conducir a una fototoxicidad excesiva debido a los potentes fotosensibilizadores (PS) y a la alta intensidad de la luz.
Los métodos actuales para monitorear la respuesta terapéutica son a menudo complejos, se realizan ex situ y se retrasan.

Objetivo del estudio:

Desarrollar un fotosensibilizador catiónico (PS) de autoinformación para el monitoreo in situ y en tiempo real de la TDP.
Investigar el mecanismo de translocación de la PS durante la apoptosis inducida por PDT.
Demostrar el potencial para el control preciso de la dosis y la reducción de los efectos secundarios en la TDP.

Principales métodos:

Síntesis de un nuevo PS catiónico, TPE-4EP+, con características de emisión inducida por agregación.
Utilizando la microscopia de fluorescencia para rastrear la translocación in situ y en tiempo real de TPE-4EP+ de las mitocondrias al núcleo durante la PDT.
Empleando la ingeniería de carga molecular para dilucidar el papel de la carga positiva en la interacción y translocación del ADN.

Principales resultados:

TPE-4EP+ exhibe emisiones inducidas por agregación, lo que permite capacidades de autoinformación.
El PS se somete con éxito a la translocación de mitocondrias al núcleo durante la apoptosis inducida por PDT, visualizada por la migración de fluorescencia.
La ingeniería de carga molecular confirmó que la interacción mejorada con el ADN, debido a la carga positiva multivalente, impulsa la translocación in situ.

Conclusiones:

El TPE-4EP+ desarrollado permite el monitoreo in situ en tiempo real de la PDT a través de la migración de fluorescencia.
Este PS de autoinforme facilita un control preciso de la dosis, mitigando la fototoxicidad excesiva y los posibles efectos secundarios.
Este enfoque allana el camino para la próxima generación de fotosensibilizadores con capacidades de diagnóstico integradas para mejorar la TDP.

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