Laboratory of Functional Polymers and Polymeric Materials

Polymer nanoreactors are actively used to increase the efficiency of delivering photosensitizers (FS) to cells — substances capable of generating highly toxic singlet oxygen as a result of excitation by an external light source. Many porphyrins and phthalocyanines exhibit the most pronounced photosensitizing properties. This property of porphyrins is used to suppress the growth of malignant tumors. A significant limitation of this method is the low transparency of biological tissues for visible light, therefore, this method is applicable for the treatment of only superficial tumors. Overcoming this limitation requires finding approaches to excite the FS without using an external light source. As such an approach, it was proposed to use the reaction between aromatic oxalates and hydrogen peroxide (peroxyoxalate reaction, PO-reaction), which is accompanied by the splitting of oxalates with the release of energy. Compounds that catalyze the decay of a high-energy intermediate (HEI) and, as a result, pass into an excited state followed by the emission of a photon are called activators (ACT). The most active substances are polyaromatic compounds such as rubrene, pentacene, 9.10diphenylanthracene, perylene, porphyrins. In this paper, it is proposed to use a porphyrin-series photosensitizer as an activator, and thereby create nanoparticles capable of generating highly toxic singlet oxygen when exposed to an environment with an increased content of hydrogen peroxide by including reaction components in the hydrophobic microphase of polymer nanoreactors of the "core-shell" type. The reaction will be most active in cancer cells, the peculiarity of whose metabolism is an increased content of hydrogen peroxide by 1-2 orders of magnitude compared to normal tissues. The aim of this project is to create polymer nanoreactors based on a biodegradable amphiphilic polymer, biocompatible oxalate and a non-toxic photosensitizer (porphyrin).

The production of biodegradable materials is one of the most sought-after areas of polymer chemistry. The ability to degrade in biological fluids and water is the most important property of carriers for controlled drug delivery, and as a result, low-toxic and easily excreted products should be formed. Polylactides have been widely used in medicine and the food industry. However, they degrade within dozens of days. In our laboratory, it is proposed to synthesize polyoxalates – esters of oxalic acid and glycols, which are intermediate products of metabolism. The use of oxalate groups has a number of advantages. Firstly, during dissociation in the first stage, oxalic acid is a strong acid with a pKa of about 1.4. Therefore, hydrolysis of oxalates should proceed about ten times faster than hydrolysis of polylactides. Secondly, the structure of polyoxalates makes it possible to further "adjust" the rate of hydrolysis by varying the pKa and hydrophobicity of the diols used. The wide variety of structures of commercially available diols and their relatively low toxicity expands the possibilities of the approach. To synthesize these polymers, we investigate the polymerization of cyclic oxalates with the opening of the cycle.