Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells.

Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer. Described herein is a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide, and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, it is shown that the activity of histone deacetylase inhibitor largazole can be switched off when stapled, but selectively switched on within cancer cells when irradiated with non-phototoxic light.