Photodynamic therapeutic efficacy of symmetrical diiodinated squaraine in in vivo skin cancer models.

BACKGROUND: Photodynamic therapy (PDT) has clinical approval for use as a minimally invasive therapeutic procedure that is able to exert selective cytotoxic activity toward malignant cells. The dye selected for our study, symmetrical diiodinated squaraine, is one of the newly developed photosensitizers. The study is designed to determine the efficacy of PDT mediated by symmetrical diiodinated squaraine in skin tumor induced Swiss albino mice. METHODS: Skin tumor was induced in mice with dimethyl benzanthracene (DMBA) and croton oil. After squaraine administration to the tumor mice, photodynamic treatment of tumors was performed using a 1000W halogen lamp corresponding to the light dose of 100J/cm2. The mice were euthanized and skin flaps and tumor tissues from the back of mice were excised for biochemical studies. The biochemical parameters analyzed include some relevant tumor markers for epithelial tissues, inflammatory markers and markers of apoptosis. The gene expression studies were done by RT-PCR. RESULTS: After two weeks of the treatment, there was significant inflammation. However at 90days after PDT, the parameters reverted to near-normal values. All marker parameters of tumor progression brought back to normal levels by PDT. Increased caspase-3 activity in PDT treated group shows that cell death might have occurred by apoptosis. The gene expression profile confirms the results. CONCLUSIONS: The results of the whole study show the therapeutic efficacy and apoptosis mediated tumor destruction by squaraine PDT.

Symmetrical diiodinated squaraine as an efficient photosensitizer for PDT applications: Evidence from photodynamic and toxicological aspects.

Photodynamic therapy (PDT) is emerging as a promising non-invasive treatment for cancers. It involves three key components; a photosensitizer, light and tissue oxygen. Even though several photosensitizers have been investigated for their use in PDT, they have several disadvantages and hence the search for more effective sensitizers has become important in recent years. The dye selected in our study - symmetrical diiodinated benzothiazolium squaraine (SQDI) - is one of the newly developed photosensitizers. The study aimed to evaluate the in vitro cytotoxicity of the dye on Ehrlich's Ascites Carcinoma (EAC) cells and to assess the in vivo toxicity on Swiss Albino mice. The EAC cells were maintained in the peritoneum of mice and used to study the dark toxicity and phototoxicity by Trypan blue dye exclusion method, estimation of Reactive Oxygen Species (ROS), caspase activity and levels of thiobarbituric acid reactive substances (TBARS). The in vitro studies revealed that the dye induces toxicity in the presence of light and mediates cell death. The in vivo part of the study, which dealt with the toxicity evaluation in the body of Swiss Albino mice, was done by analyzing the parameters like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), lactate dehydrogenase (LDH), creatine kinase (CK) and alkaline phosphatase (ALP). No significant change was observed in the above mentioned parameters in the dye administered group when compared to control. Altogether, this experiment indicates that the SQDI selected for our study may be used as an efficient photosensitizer for PDT applications and does not elicit acute toxicity to normal tissues in the absence of light.

Asymmetric squaraine dyes: spectroscopic and theoretical investigation.

A joint experimental and theoretical study is presented of two asymmetric squaraine dyes and their parent symmetric dyes. The definition of reliable essential-state models for asymmetric squaraines sheds light on the intriguing spectroscopic behavior of this class of molecules, showing inverted and normal solvatochromism in absorption and emission, respectively. This behavior is related to charge redistribution in the excited state, with important implications for optimal design of asymmetric dyes for solar cell applications.