Selective Ablation of β-Galactosidase-Expressing Cells with a Rationally Designed Activatable Photosensitizer

We have developed an activatable photosensitizer capable of specifically inducing the death of beta-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing beta-galactoside as a targeting substituent, we designed and synthesized HMDESeR-beta Gal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, beta-galactosidase efficiently converted HMDESeR-beta Gal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible-wavelength absorption and the ability to generate singlet oxygen (O-1(2)). When HMDESeR-beta Gal was applied to larval Drosophila melanogaster wing disks, which express beta-galactosidase only in the posterior region, photoirradiation induced cell death in the beta-galactosidase-expressing region with high specificity.