Preparation and sonodynamic activities of water-soluble tetra-α-(3-carboxyphenoxyl) zinc(II) phthalocyanine and its bovine serum albumin conjugate

• A non-covalent BSA conjugate of ZnPcC4 (ZnPcC4–BSA) was prepared.
• ZnPcC4 and ZnPcC4–BSA exhibited sonodynamic activities against HepG2 cells.
• ZnPcC4–BSA showed a higher sonodynamic activity.
• The albumin conjugates of ZnPcs can serve as promising sonosensitizers for SDT.

Sonodynamic therapy (SDT) is a new approach for cancer treatment, involving the synergistic effect of ultrasound and certain chemical compounds termed as sonosensitizers. A water-soluble phthalocyanine, namely tetra-α-(3-carboxyphenoxyl) zinc(II) phthalocyanine (ZnPcC4), has been prepared and characterized. The interactions between ZnPcC4 and bovine serum albumin (BSA) were also investigated by absorption and fluorescence spectroscopy. It was found that there were strong interactions between ZnPcC4 and BSA with a binding constant of 6.83 × 107 M−1. A non-covalent BSA conjugate of ZnPcC4 (ZnPcC4–BSA) was prepared. Both ZnPcC4 and ZnPcC4–BSA exhibited efficient sonodynamic activities against HepG2 human hepatocarcinoma cells. Compared with ZnPcC4, conjugate ZnPcC4–BSA showed a higher sonodynamic activity with an IC50 value of 7.5 μM. Upon illumination with ultrasound, ZnPcC4–BSA can induce an increase of intracellular reactive oxygen species (ROS) level, resulting in cellular apoptosis. The results suggest that the albumin conjugates of zinc(II) phthalocyanines functionalized with carboxyls can serve as promising sonosensitizers for sonodynamic therapy.