Cellular inactivation and antitumor efficacy of a new zinc phthalocyanine with potential use in photodynamic therapy.
The aim of the present study was to evaluate the photodynamic efficacy of a novel phthalocyanine derivate 2,3,9,10,16,17,23,24-octakis[(N,N-dimethylamino) ethylsulfanyl]phthalocyaninatozinc(II) (referred here as S1) using MCF-7c3 human breast cancer cells and the LM2 adenocarcinoma subcutaneously implanted in Balb/c mice as experimental models. The S1-l-alpha-dimyristoyl-phosphatidylcholine liposome was selected as the best delivery system because it showed greater internalization into cells (35 nmol/10(6) cells), relative to other liposomes. After 3 h incubation S1 was partially localized in lysosomes, the compartment that represented its primary photodamage site. The S1 treated cultures also revealed a degree of mitochondrial morphology alteration. Indeed, S1 leads to photokilling of the cells with different efficacies indicating that cell photoinactivation was dependent on both the phthalocyanine concentration and the light dose applied. Analyses of morphology and nuclear condensation level indicated that some of the cells exposed to photodynamic therapy were undergoing apoptosis within 8h after treatment. To assess the in vivo effectiveness of S1, animals bearing tumors were treated with 0.2mg/kg S1 followed 24h later by 108 J cm(-2) light at 600-800 nm and 60 mW cm(-2),while other animals served as controls (no treatment, light alone, or S1 alone). All S1 treated tumors and none of the controls exhibited complete or partial responses, and these responses continued for the entire observation period of 12 days. Evaluation of tumor size showed that the treatment effectively delayed tumor growth. Light microscopy investigations of irradiated tumor specimens showed that S1 causes an early direct damage of malignant cells, largely via processes leading to random necrotic pathways.
Vittar
Natalia B Rumie
NB
Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal N(ro) 3, 5800 Río Cuarto, Córdoba, Argentina.
Prucca
Cesar G
CG
Strassert
Cristian
C
Awruch
Josefina
J
Rivarola
Viviana A
VA
D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D003470:Culture Media; D003624:Darkness; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D042541:Intracellular Space / Q000378:metabolism; D054833:Isoindoles; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D010778:Photochemotherapy / Q000379:methods*; D012996:Solutions; D013050:Spectrometry, Fluorescence; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D017967:Zinc Compounds
D003470:Culture Media; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D012996:Solutions; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine