Biodistribution and phototherapeutic properties of Zinc (II) 2,9,16,23-tetrakis (methoxy) phthalocyanine in vivo.
Photodynamic therapy (PDT) was investigated using the phthalocyanine photosensitizer Zinc (II) 2,9,16,23-tetrakis (methoxy) phthalocyanine (ZnPc(OCH(3))(4)) on BALB/c mice. Animals bearing tumor were treated with 0.2mg/kg body weight (bw) ZnPc(OCH(3))(4) and 24h later were irradiated with 70, 140 and 210 J/cm(2) of visible light from a source delivering 39 mW/cm(2). In this study, we have tested the efficiency of ZnPc(OCH(3))(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(OCH(3))(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(OCH(3))(4). In the tumor sections for biochemical studies, apoptosis was visualized by activation of caspase-3. ZnPc(OCH(3))(4)-PDT tumors showed a significant delay in growth as compared to untreated control mice. In all cases, ZnPc(OCH(3))(4)-PDT-treated tumors showed a significant regression. The results indicated a dramatic decrease of tumors size after 10 days post-irradiation with 210 J/cm(2) and no recurrence of the disease was detectable within at least 90 days. The phototherapeutic agent ZnPc(OCH(3))(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(OCH(3))(4)-PDT may be of particular importance in the treatment of accessible malignancies.
Yslas
E Inés
EI
Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro 3, X580BYA Río Cuarto, Argentina. eyslas@exa.unrc.edu.ar
Prucca
César
C
Romanini
Silvia
S
Durantini
Edgardo N
EN
Bertuzzi
Mabel
M
Rivarola
Viviana
V
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005260:Female; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D054833:Isoindoles; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D016896:Treatment Outcome; D017967:Zinc Compounds
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine