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

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