Phenylthio-substituted phthalocyanines as new photosensitizers for photodynamic therapy

Abstract

Current work is devoted to investigation of tetra-3-phenylthio-tetra-5-t-butylphthalocyanine [(PhS)₄(t-Bu)₄PcH₂], aluminium hydroxyde tetra-3-phenylthiophthalocyanine [(PhS)₄PcAlOH] and zinc tetra-3-phenylthiophthalocyanine [(PhS)₄PcZn] as potential photosensitizers of near-infrared range. Investigations were performed on F₁ mice bearing Erlich tumor. Photosensitizers were administered intravenously in liposomal form at doses of 4-10 mg/kg. Dynamic and selectivity of sensitizers' accumulation in tumor were estimated in vivo from fluorescence and absorption spectra of sensitized tissue. Photosensitizers have shown high selectivity of accumulation in tumor comparing to normal tissue of mice. Maxima of selectivity for (PhS)₄(t-Bu)₄PcH₂, (PhS)₄PcZn and (PhS)₄PcAlOH achieve the values up to 2.5:1, 5:1 and 8:1 respectively. All photosensitizers completely clear from the normal tissue in 7-8 days. For PDT investigations tumors were irradiated using 732 nm laser with power density of 100-500 mW/cm² and light dose density up to 400 J/cm². The photodynamic efficiency was estimated using the parameter of tumor growth inhibition (TGI). All photosensitizers had shown high photodynamic efficiency of relatively large tumors. PDT using (PhS)₄PcAlOH and (PhS)₄(t-Bu)₄PcH₂ caused pronounced TGI exceeding 80%. Using (PhS)₄PcZn caused moderate TGI of 60%. Investigations have shown that liposomal forms of phenylthiosubstituted phthalocyanine derivatives may be used to develop new efficient photosensitizers for PDT.