Enhanced Photodynamic Efficacy of Zinc Phthalocyanine by Conjugating to Heptalysine

Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of <i>Pc</i> ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)_<i>n</i> (<i>n</i> = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive <i>in situ</i> method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)₇ has the highest photodynamic efficacy compared to the other conjugates investigated