Activatable Photosensitizer for Targeted Ablation of lacZ-Positive Cells with Single-Cell Resolution

[Image: see text] To achieve highly selective ablation of lacZ-positive cells in a biological milieu in vivo, we developed an activatable photosensitizer, SPiDER-killer-βGal, targeted to β-galactosidase encoded by the lacZ reporter gene. Hydrolysis of SPiDER-killer-βGal by β-galactosidase simultaneously activates both its photosensitizing ability and its reactivity to nucleophiles, so that the phototoxic products generated by light irradiation are trapped inside the lacZ-positive cells. The combination of SPiDER-killer-βGal and light irradiation specifically killed lacZ-positive cells in coculture with cells without lacZ expression. Furthermore, β-galactosidase-expressing cells in the posterior region of cultured Drosophila wing discs and in pupal notum of live Drosophila pupae were selectively killed with single-cell resolution. This photosensitizer should be useful for specific ablation of targeted cells in living organisms, for example, to investigate cellular functions in complex networks.