Photosensitizer chlorophyllin in the treatment of oncopathologies

The antitumor effect of photodynamic therapy (PDT) consists of a combination of direct toxic damage to tumor cells with indirect mechanisms of suppression of tumor vascularization and activation of the immune response. The combination of a photosensitizer (PS) and light in the presence of oxygen leads not only to selective tissue destruction, but also to long-term control over the first cell proliferation. The presence and severity of the above elements of selective destruction largely depends on the properties of the PS. One of the most important directions for increasing the efficiency of PDT is the synthesis of PSs with increased selectivity of accumulation in the pathological site. It has been shown that PSs of the chlorin series have similar selectivity for target cells, low toxicity, and good photophysical properties. Currently, the drug Photoditazin is used for PDT for oncological diseases. Chlorophyll (phytolesterified magnesium porphyrin) is similar in action to bilirubin, which is a candidate molecule responsible for the body's antioxidant defenses.

In this study, it was shown that chlorophyllin is able to accumulate in pathological tissues and influence to the P450 cytochrome. The prooxidative and antiproliferative effects of chlorophyllin as a component of a drug «OXYChlorophyll» was studied in the models «in vitro» and «in vivo». Chlorophyllin provides good absorption, digestibility, stability and accurate transport to target cells. It has been shown to produce antiproliferative effects in Ehrlich's ascites carcinoma (EAC) to the cell line in a dose-dependent manner. Chlorophyllin have been observed to increase the production of reactive oxygen species (ROS) and enzymatic activity of EAC cells, including the production of mitochondrial/whole-cell ROS, and alter the ratio of reduced-to-oxidized glutathione. Importantly that «Chlorophyll OXY»-mediated suppression of EAC cell viability has been replicated in «in vivo» experiments, where its administration a resulted in the reduction of tumor size in mice. In conclusion, this data suggests that chlorophyllin mediated changes on the redox status of cancer cells leads to a decrease in its proliferation.

Funding: The reported study was funded by RFBR, project number 20-33-90185.