Biodistribution and phototherapeutic properties of Zinc (II) 2,9,16,23-tetrakis (methoxy) phthalocyanine in vivo

Summary 

Photodynamic therapy (PDT) was investigated using the phthalocyanine photosensitizer Zinc (II) 2,9,16,23-tetrakis (methoxy) phthalocyanine (ZnPc(OCH₃)₄) on BALB/c mice. Animals bearing tumor were treated with 0.2mg/kg body weight (bw) ZnPc(OCH₃)₄ and 24h later were irradiated with 70, 140 and 210J/cm² of visible light from a source delivering 39mW/cm². In this study, we have tested the efficiency of ZnPc(OCH₃)₄ liposomal formulation on mice. Biodistribution studies were performed in tumor-free mice and tumor-bearing mice at various time points up to 24h after ZnPc(OCH₃)₄-PDT treatment. The tumor sizes were evaluated over different period in parallel experiments. The maximal efficiency and selectivity of photosensitizer accumulation in tumor tissue take place at 24h after drug administration of 0.2mg/kg bw ZnPc(OCH₃)₄. In the tumor sections for biochemical studies, apoptosis was visualized by activation of caspase-3. ZnPc(OCH₃)₄-PDT tumors showed a significant delay in growth as compared to untreated control mice. In all cases, ZnPc(OCH₃)₄-PDT-treated tumors showed a significant regression. The results indicated a dramatic decrease of tumors size after 10 days post-irradiation with 210J/cm² and no recurrence of the disease was detectable within at least 90 days. The phototherapeutic agent ZnPc(OCH₃)₄ demonstrated preferential accumulation in tumor in comparison with skin tissues, except in the case of kidney. The ratio of tumor/skin tissues ranged a value of 8. These results suggest that ZnPc(OCH₃)₄-PDT may be of particular importance in the treatment of accessible malignancies.

Abbreviations: HE, haematoxylin-eosin, PBS, phosphate-buffered saline, Pc, phthalocyanine, PDT, photodynamic therapy, PS, photosensitizers, THF, tetrahydrofuran

Keywords: Photodynamic therapy, Photosensitizers, Phthalocyanine, Tumors, Apoptosis