Photodegradation of carbonic anhydrase IX via a binding-enhanced ruthenium-based photosensitizer

Carbonic anhydrase IX (CAIX) is overexpressed in many cancer types. Herein, a CAIX targeting and binding-enhanced ruthenium-based photodegrader, Ru-dppz-CAi, is constructed by conjugating the photosensitizer with the inhibiting group via a rotatable moiety. The binding of Ru-dppz-CAi and CAIX leads to significant enhancement in the emission and photosensitizing properties. Ru-dppz-CAi can photodegrade CAIX both in vitro and in living cells, which significantly inhibits its catalytic activity. The protein photodegradation method may provide new strategies for the development of tools for protein functional studies.