Drug delivery and bioimaging using theranostic lipid nanoparticles

Abstract

The natural compound 4-Methylesculetin (4-ME) belonging to the coumarins class has relevant results in experimental models of intestinal inflammation with potential use in the treatment of inflammatory bowel diseases and cancer. However, factors as low solubility in water and its physicochemical instability are still obstacles to consider the relevance of this compound as a new treatment product. Such characteristics require the use of adequate carriers capable of guaranteeing its therapeutic efficiency. In this context, previous study has been performed within the postdoctoral project FAPESP (number 2020/15185-0), evidencing the photophysical properties of 4-ME at relevant physiological conditions (different pH) and its interaction in biomimetic cell systems. The next step of this project, to be developed within Dr. Jonathan Brewer's group, at University of Southern Denmark, aims the use of 4-ME as a theranostic product based on its encapsulation in lipid-formed nanoparticles to be used as nanocarriers. In addition, biophotonic techniques will be explored to obtain a complete understanding of coumarin activity (comparing the application in free form and encapsulated) in tumor cells lines. The coumarin-loaded nanocarrier will provide simultaneous tumor targeting, molecular imaging of drug delivery and investigation of the therapeutic fallout. Brewer and his group are specialist in the bioimaging field and have published relevant papers, especially by using super-resolution microscopy techniques. We highlight the Stimulated Emission Depletion (STED) and Minimal Photon Fluxes (MINFLUX) microscopies, an extremely new and advanced technique that provide three-dimensional resolution at the size scale of fluorescent probes. Besides, with this BEPE project will be possible to explore the particular Spatial Transcriptomics technology named Multiplexed Error-Robust Fluorescence in Situ Hybridization (MERFISH) that can achieve the single-cell resolution, enabling the mapping of the spatial organization of the RNA profiling in cultured cells. This will provide us to understand the effect of the coumarin treatments on the cells. The collaboration with Brewer's group will be important for the progress of our research regarding the encapsulation of 4-ME and enhancing its efficiency, in addition the applicant will gain great experience in the most advanced microscopic techniques available. (AU)