Amplification of bioorthogonal 'click-to-release' prodrugs

Bioorthogonal chemistry refers to a chemical reaction taking place within a living system, without interfering with any native, biochemical processes. Over the last 20 years, research in this area has exploded, with initial applications in protein labelling and cellular imaging expanding to include cell engineering, materials science, protein isolation and drug delivery. Bioorthogonal prodrug activation strategies that make use of the hydrolytic instability of 1,3-dipolar cycloaddition adducts following reaction of azides with TCO provide exciting possibilities for drug delivery. However, drug release in vivo was insufficient meaning further optimisation and amplification strategies are required.