ИСТИНА

Photodynamic therapy (PDT) is a quickly emerging modality of treatment which employs the photochemical interaction of light, photosensitizer and oxygen. Photosensitizer localized in tumor and exposed to laser can transform molecular oxygen into highly toxic singlet state. The opacity of living body is a severe limitation of the technique. PDT is suitable only for tumors accessible to light guide. We have designed a new light-free approach of photosensitizer excitation employing energy of chemiluminescent (CL) reaction between biochemically generated hydrogen peroxide and aromatic oxalates running in a living cell. This reaction is referred to as PeroxyOxalate ChemiLuminescent (PO-CL) reaction and might be a source of singlet oxygen. 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 CL particles based on dimethylphthalate emulsion in water stabilized with Pluronic L64 and containing hematoporphyrin derivative as a photosensitizer. The active component was represented by oligooxalate synthesized via polycondensation of oxalyl chloride with oligo(propylene oxide) and bishenol A. Obtained particles possess negative zeta potential due to oxalate hydrolysis and exposition of carboxylic groups on the particles surface. To facilitate oligooxalate permeation through negatively charged cell membranes, its electrostatic complexes with poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) were prepared. Turbidimetry and dynamic light scattering studies revealed formation of electroneutral or slightly positively charged particles exhibiting high CL quantum yields. Anti-tumor activity of optimized CL formulations containing the polycation were tested in cell cultures. Acknowledgement The work was supported by the Russian Science Foundation (project 14-15-00391).