Microneedle array-Mediated Combinatorial Photodynamic Raman Nanotheranostics for simultaneous Cancer Diagnosis and Therapy

Descripción del proyecto

Un nuevo método activado por la luz para el tratamiento del cáncer de piel

El cáncer de piel es la neoplasia maligna más frecuente. Dado que se prevé un aumento de su prevalencia, existe una necesidad urgente de tratamientos más eficaces y accesibles. Una alternativa muy prometedora es la terapia fotodinámica, que utiliza moléculas activadas por la luz para destruir las células cancerosas. No obstante, su eficacia se ve limitada por la escasa penetración de la luz en la piel. En el proyecto MNA-Cancer, financiado por las acciones Marie Skłodowska-Curie, se pretende desarrollar nanopartículas que respondan a los rayos X en lugar de a la luz visible. Unas microagujas solubles permiten administrar estas nanopartículas con precisión en las zonas tumorales, generando moléculas capaces de destruir el cáncer en el interior del tejido. El método se evaluará en modelos preclínicos mediante seguimiento en tiempo real. Se prevé que mejore tanto el diagnóstico como el tratamiento del cáncer de piel.

Objetivo

Skin cancer (SC) is the most common human malignancy with rapidly increasing incidence due to numerous environmental, genetic, and metabolic reasons. Highly effective, convenient, inexpensive and widely deployable SC diagnostic and therapies are urgently needed to address this public health issue. Photodynamic Therapy (PDT) is one of the available non-invasive SC treatments that involves the combination of photosensitizer (PS), light and molecular oxygen to elicit cancer cells death by generation of reactive oxygen species (ROS). Despite its potential, PDTs effectiveness is limited by issues such as photobleaching, self-aggregation of PSs, and inadequate visible light penetration into skin tissues due to absorption by photoreceptive chromophores, necessitating further research and development.
Our proposed approach introduces a novel process using X-ray active nanotheranostic photosensitizers (NT@PS), which are developed by combining scintillators metal (e.g. Gd) with PSs (e.g. Rose Bengal) to enhance ROS production, photostability, and offer persistent luminescence properties. The outermost layer of skin limits the passive transport of PSs, therefore microneedle arrays (MNAs) technology will be used to achieve effective NT@PS delivery to deep SC sites. MNAs are an emerging drug delivery platform that addresses the limitations of conventional needle-based systems. Upon successful delivery and diffusion of NT@PS through the MNAs device, X-PDT will be assessed in-vivo using subcutaneously implanted SC cells, with real-time monitoring through Raman spectroscopy. Overall, this project aims to revolutionize skin cancer diagnosis and treatment through the development of an innovative combinatorial nanotheranostic system.
Additionally, this fellowship and mentorship from leading researcher will lay a solid foundation for the fellow independent research career, providing access to a dynamic research environment, comprehensive training and a robust collaboration network