ABSTRACT
The efficiency of photodynamic therapy with photosensitizer Tiosens (Russia) was evaluated in mono- and combined therapy of rats with malignant gliomas (glioblastoma 101/8, oligodendroglioma 14-4-9, and C6 glioma). The efficiency of photodynamic monotherapy was not high: the animals died from brain edema developing in tumor tissue and in the adjacent normal cerebral tissue. Pathomorphological studies of tumor tissue detected necrosis and apoptosis, destruction of vessels with hemorrhages, and vascular thrombosis. Combined therapy for malignant gliomas including Tiosens photodynamic therapy and subsequent temodal or lysomustine chemotherapy, was the most effective. In glioblastoma 101/8, combined therapy with lysomustine or temodal led to prolongation of the lifespan by 127 %; 62.5 and 50 % rats were cured, respectively; in oligodendroglioma 14-4-9, animal lifespan was prolonged by 80 and 60 %, with 43 and 45 % rats cured, respectively. Glioma C6 was least sensitive to therapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Oligodendroglioma/drug therapy , Photochemotherapy , Animals , Animals, Outbred Strains , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Drug Screening Assays, Antitumor , Humans , Indoles/administration & dosage , Neoplasm Transplantation , Nitrosourea Compounds/administration & dosage , Organometallic Compounds/administration & dosage , Photosensitizing Agents/administration & dosage , Rats, Wistar , TemozolomideABSTRACT
We studied the possibility of using liposomal forms of hydroxyaluminium tetra-3-phenylthiophthalocyanine as a near infrared band photosensitizer. Experiments on mice with solid Ehrlich tumor and subcutaneously transplanted P-388 leukemia revealed high selectivity of accumulation of the photosensitizer in tumors in comparison with normal tissues and high photodynamic activity of the preparation. This photosensitizer can be used as the basis for creating an effective preparation for photodynamic therapy and fluorescent diagnosis.
Subject(s)
Carcinoma, Ehrlich Tumor/drug therapy , Indoles/therapeutic use , Leukemia P388/drug therapy , Organometallic Compounds/therapeutic use , Photochemotherapy , Photosensitizing Agents/therapeutic use , Animals , Carcinoma, Ehrlich Tumor/diagnosis , Leukemia P388/diagnosis , Mice , Neoplasm TransplantationABSTRACT
Comparative studies of oxygen consumption, changes of photosensitizer fluorescence, and photodestruction of erythrocytes, and photodestruction of oxygen transport protein hemoglobin were performed during photodynamic reaction in whole and hemolyzed blood with phthalocyanines, chlorines, porphyrins, and methylene blue photosensitizers in vitro and in selected cases in vivo. The present work deals with the investigation of blood oxygen saturation SO2 and photosensitizer fluorescence during and immediately after light irradiation in the photodynamic therapy process. It has been observed that SO2 behavior strongly correlates with the type of photosensitizer. The decrease of photosensitizer fluorescence (photobleaching) during light irradiation can be followed by the recovery of the photosensitizer fluorescence immediately after interruption of the irradiation within 6-8 min. The levels of photodestruction of erythrocytes in whole blood and photodestruction of hemoglobin in hemolyzed blood in combination with the above photosensitizers reveal the influence of photodynamic reactions upon the ability of blood to transport oxygen. Maximal photohemolysis activity has been found with chlorine p6 photosensitizers.
Subject(s)
Blood/radiation effects , Carcinoma, Ehrlich Tumor/blood , Heart Diseases/blood , Photochemotherapy , Photosensitizing Agents/administration & dosage , Absorption , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Erythrocytes/drug effects , Erythrocytes/metabolism , Erythrocytes/radiation effects , Female , Fluorescence , Heart Diseases/drug therapy , Humans , Injections, Intravenous , Light , Mice , Mice, Inbred C57BL , Oxygen Consumption/radiation effects , Photosensitizing Agents/pharmacokineticsABSTRACT
Covalently bound conjugates of alpha-fetoprotein (AFP) and epidermal growth factor (EGF) with photoheme (PH), 3-desvinyl-3-formylchlorine p6 (Chl p6), chlorine e6 (Chl e6), aluminum disulfochloride phthalocyanine (PC(Al)), and cobalt octa-4,5-carboxyphthalocyanine (teraphthal, TP(Co)) were synthesized. Their molar ratios were 1:4 for AFP-cytotoxin conjugates (cf. 1:10 for AFP-TP(Co)) and 1:2 for EGF conjugates (cf. 1:1 for EGF-PC(Al)). Dark toxicity of both protein conjugates with PH, chlorines, and PC(Al) was much lower than their phototoxicity. Studies on phototoxicity demonstrated that PC(Al) conjugates with AFP and EGF and also EGF-Chl p6 were the most effective. The cytotoxic activity (CTA) of AFP-PC(Al) and EGF-Chl p6 was 80% and of EGF-PC(Al) 64% higher than the CTA of the free drugs. Conjugates with TP(Co) were much more toxic on their activation with ascorbic acid (AA): in the presence of AA the CTA of AFP-TP(Co) and of EGF-TP(Co) was 19 and 61.1% higher, respectively, than the CTA of the free TP(Co).
