Development of carbonic anhydrase IX-targeting molecular-targeted photodynamic therapy.

The efficacy of molecular-targeted photodynamic therapy (MT-PDT) targeting carbonic anhydrase (CA) IX, a cancer-specific molecule, was demonstrated. CA ligand-directed photosensitizers 1-3 were evaluated for their ability to deactivate CAIX protein in cells. Compounds 2 and 3 selectively deactivated CAIX protein under 540 nm light without affecting internal standard proteins. Mechanistic studies revealed that compound 3 not only induced CAIX-selective light inactivation via singlet oxygen but also induced cell membrane damage, resulting in an anti-tumor effect. In vivo studies of CAIX-targeting MT-PDT revealed that treatment with compound 3 followed by light irradiation exhibited remarkable anti-tumor activity, leading to tumor degeneration and necrosis.