Photodynamic effects of silicon phthalocyanines in model cells and tumors (Invited Paper)

A series of silicon and aluminum phthalocyanines is being investigated in this laboratory for their potential as photosensitizers for photodynamic tumor therapy (PDT). Of these, one of the silicon phthalocyanines [SiPc(OH)OSi(CH 3 ) 2 (CH 2 ) 3 N(CH 3 ) 2 ] (Pc IV) has proven to be highly efficient in a series of in vitro assays and in PDT in vivo. When compared to sulfonated or non-sulfonated aluminum phthalocyanine and/or Photofrin II, Pc IV produced greater effects at lower concentrations in a clonogenic assay with V79 cells, and in photoenhancement of lipid peroxidation in human erythrocyte membranes. Physiological responses of treated cells in vitro appeared similar to those produced by PDT with other sensitizers; however, the responses, such as the induction of apoptosis in murine lymphoma, occurred with greater efficiency when Pc IV served as photosensitizer. In order to evaluate the efficacy of Pc IV in vivo, the dye was suspended in corn oil or incorporated into liposomes and injected intraperitoneally into C3H mice bearing RIF-1 tumors. Pharmacokinetic studies showed efficient uptake of Pc IV into the tumor, as well as into liver and kidney. For PDT, tumors were irradiated with 675 nm light from an argon-pumped dye laser. Treatment of tumors up to 100 mm 3 with 1.0 mg/kg Pc IV and 135 J/cm 2 produced ablation of the tumor within 48 hours. Tumors > 200 mm 3 could be ablated with 2.0 mg/kg Pc IV. The data suggest that Pc IV may be a highly efficient photosensitizer for tumor PDT.