ИСТИНА

Photodynamic therapy (PDT) is a quickly emerging modality of treatment which employs the photochemical interaction of three components: light, photosensitizer and oxygen. Photosensitizer molecules localized in tumor and exposed to laser can transform molecular oxygen into high-toxic reactive oxygen species (ROS) such as singlet oxygen. This technique permanently entered clinical practice for the treatment of superficial tumors and festering wounds. Despite tremendous progress in new technical development of all components as well as understanding of the biophysical mechanism of PDT, several limitations of PDT remain. The most severe limitation is the opacity of living body making PDT suitable only for superficial tumors or tumors accessible to light guide and hindering the treatment of solid and metastatic tumors. We have designed a new light-free approach of photosensitizer excitation employing energy of chemiluminescent reaction between biochemically generated hydrogen peroxide and aromatic oxalates running in a living cell. This reaction is usually referred to as PeroxyOxalate ChemiLuminescent (PO-CL) reaction might be a source of singlet oxygen. In the work, we have proved that this approach is successful in killing tumor cells pretreated with inducers of oxidative stress in vitro. For this purpose, we employed chemiluminescent particles based on dimethylphthalate emulsion in water stabilized with Pluronic L64 and containing hematoporphyrin derivative as a photosensitizer. The active component was represented by oligomeric oxalate synthesized via polycondensation of oxalyl chloride with the mixture of oligo(propylene oxide) and bishenol A. It was revealed that obtained particles possess negative zeta potential, probably due to oxalate hydrolysis and exposition of carboxylic groups on the particles surface. This feature can impede the particles interaction with negatively charged cell membranes. Therefore, to facilitate oligooxalate permeation through cell membranes, its electrostatic complexes with poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) were prepared. Measurements of zeta potentials revealed slow kinetics of equilibration of colloidal particles near the point of zero charge. Turbidimetry and dynamic light scattering studies revealed formation of electroneutral or slightly positively charged particles exhibiting high quantum yield of chemiluminescence. According to the results of the work polycation at high concenrations suppresses the chemiluminescence efficiency. The influence of the polycation on the oligooxalate stability in aqueous environment was investigated. Anti-tumor activity of optimized chemiluminescent formulations containing the polycation were tested in cell cultures. Acknowledgement The work was supported by the Russian Science Foundation (project 14-15-00391).