Preclinical Evaluation of Symmetrical iiodinated Squaraine Dye on Experimental Animal Models.

Abstract

Photodynamic therapy involves administration of a tumor localizing photosensitizing agent, followed by the activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiological processes that cause irreversible photo damage to the tumor tissue. Only a few photosensitizers have received official approval around the world. But they are with some adverse side effects. Because of these draw backs search for new photosensitizers is in progress. The dye selected in our study-Symmetric diiodinated squaraine-is one of these newly developed photosensitizers. We have examined the in vivo distribution of the dye on normal and skin tumor induced animal models to check the retention time of the dye. The mechanism of action of photosensitizers in selective killing of cancer cells involves the generation of oxidative stress whereby the malignant cells are damaged, in presence of light of appropriate wavelength. Thus we also intended to study whether there is the initiation of oxidative damage in the normal tissues in the body of dye injected mice in the absence of light. The results show that maximum amount of the dye was accumulated in the different organs of the body 4 h after the administration. The compound is tumor specific since after 24 h of injection, it was retained only in the tumor site and in the immediate surroundings of the tumor. This shows the selectivity of the dye to tumor tissue. The administration of the squaraine dye in the system induces no significant change in the level of lipid peroxidation products and activity of antioxidant enzymes when compared to the control mice. This indicates that the squaraine dye does not induce any oxidative stress to the normal tissues in the body and hence the dye can be safely used for photodynamic therapy.

Polymethine dyes for PDT: recent advances and perspectives to drive future applications

“…Since the cytochrome C release to the cytosol, due to the significant alteration of mitochondrial membrane permeability, is considered a crucial event in the mitochondria mediated pathway of apoptosis, they were able to confirm the crucial role of SQ in the induction of cell apoptosis [103,104]. At the same time, the in vivo biodistribution of the dye on normal and skin tumor induced animal models has been investigated to evaluate the retention time of the dye [101]. After 24 h of injection, the dye has been clearly detected in the tumor site and in the immediate surroundings of the tumor, while no trace of SQ has been observed in the healthy tissues, confirming the selectivity of the dye for the tumor cells compared to the normal ones and the rapid clearance from the body.…”

“…As far as squaraines are concerned, since Abraham et al [100] reported the first in vivo experiments on phloroglucinol SQ 2c as promising photosensitizers in PDT, only a limited number of works have reported the PDT potentiality of these PSs in vivo [43,101,102]. The bis(3,5-diiodo-2,4,6trihydroxyphenyl) squaraine (2c) proved the ability to reduce the tumor size after PDT in the treatment of skin cancer in experimental mice models [100,102], focusing the attention on the localization of the PS in the cellular environment.…”