Thermally-Activated Delayed Fluorescence Nanoparticle Assemblies for Photodynamic Therapy

Photodynamic Therapy (PDT) is a non-invasive cancer treatment that uses light-activated, photosensitising dyes to generate highly reactive oxygen species (ROS) within a localised biological environment, leading to the destruction of cancer cells, while sparing surrounding healthy tissue. The PDT process comprises two stages: administration of a dye, followed by irradiation with light. Since ROS is only generated at the light-activated sites, tissue destruction is highly localised and side effects are significantly reduced. The potential for PDT is clear. However, for all this potential, widespread adoption has stagnated: only three dyes have been approved for cancer treatment globally, while the dye most commonly studied in clinical trials - Photofrin - is a statistical mixture of oligomeric porphyrins. Dye design for many years has focussed on porphyrins derived from Photofrin, and more recently phosphorescent ruthenium(II) polypyridyl complexes. However, in this proposal, a new design strategy is proposed: thermally-activated delayed fluorescence (TADF) dyes are the targets of interest. These are all-organic compounds that have small singlet-triplet energy gaps, which causes them to undergo rapid intersystem crossing and reverse intersystem crossing between the singlet and triplet states. By accessing the triplet state, they can readily generate singlet oxygen, which is one form of ROS, marking their potential for PDT. These compounds have been widely used organic device applications, but their uses in biological applications such as imaging and particularly PDT are much less. This proposal addresses this gap, using novel, cationic, near-IR emitting, TADF dyes. Their delivery to cells will be achieved using biocompatible, Extracellular Vesicles (EVs), which have been shown to be improved PDT delivery agents over other methods.