The in vitro photo-sonodynamic combinatorial therapy activity of cationic and zwitterionic phthalocyanines on MCF-7 and HeLa cancer cell lines

The syntheses and characterization studies of zwitterionic 2,9,16,23-tetrakis-(N-propane sultone-morpholino) zinc(II) (4) and 2,9,16,23-tetrakis-(2,5-dimethyl-4-(N-propane sultone-morpholinomethyl))-phenoxy zinc(II) (6) phthalocyanines are reported in this work. The photophysical properties, reactive oxygen species (ROS) generation and in vitro anticancer photodynamic (PDT), sonodynamic (SDT), and photo-sonodynamic combination (PSDT) therapy activities of the Pcs were studied and compared to their cationic counterparts: (2,9,16,23-tetrakis-(N-methyl-morpholino) Zn(II)Pc, 3), (2,9,16,23-tetrakis-(2,5-dimethyl-4-(N-methylmorpholine)-phenoxy) Zn(II)Pc, 5). The cationic Pcs maintained higher anticancer activity for all treatment types and had higher ROS generation compared to the zwitterionic Pcs. Singlet oxygen and hydroxyl radicals were generated during ultrasound and combination irradiations of the Pcs. The zwitterionic Pcs also generated carbon radicals under ultrasound and combination irradiations. The ability of the Pcs to generate ROS is essential for PDT, SDT and PSDT, thus making these Pcs potential anticancer probes for these treatment types. Furthermore, the Pcs demonstrated the ability to bind to bovine serum albumin protein.