Free Radical-mediated Targeting and Immobilization of Coupled Payloads

Targeted drug delivery is a promising approach to enhance the accumulation of therapies in diseased tissues while limiting off-site effects. Ligand-receptor interactions are traditionally identified to deliver therapies, and although specific, this can be costly and often suffers from limited sensitivity. An emerging approach is to target intermediary species that modulate disease progression. Here, we propose novel methods of targeting therapies by using native free radicals as a homing signal. Elevated concentrations of free radicals are a characteristic comorbidity of many different diseases. In polymer chemistry, free radicals are frequently used to initiate crosslinking reactions. We proposed that free radicals elevated in injury sites are capable of inducing crosslinking of acrylate groups on polymer chains. Coupling payloads to the polymer then allow for specific targeting of therapies to areas with elevated free radicals. We demonstrate proof-of-principle of this approach. Reactive oxygen species (ROS) initiated crosslinking of acrylated PEGs, which immobilized a fluorescent payload within tissue mimics. The cross-linking efficiency and immobilization potential varied with the polymer chain length, suggesting that a tuneable platform can be achieved. Together these results provide promising proof-of-concept for using free radicals to specifically target and sustain nearly endless payloads to disease sites.