Nitric oxide (NO) is an important signaling molecule that plays a key role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs) generating NO are widely used to treat cardiovascular diseases. However, the involvement of DNICs in the metabolic processes of the cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and rat cardiomyocytes. Moreover, DNICs demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in rat cardiomyocytes (H9c2 cells). Data revealed that the DNICs compounds modulate the mitochondria function by decreasing the mitochondrial membrane potential (ΔΨm). Results of flow cytometry showed that DNICs were not affected the proliferation, growth of fibroblasts. In addition, this study showed that DNICs did not affect glutathione levels and the formation of reactive oxygen species in cells. Moreover, results indicated that DNICs maintained the ATP equilibrium in cells. Taken together, these findings show that DNICs have protective properties in vitro. It was further suggested that DNICs may be uncouplers of oxidative phosphorylation in mitochondria and protective mechanism is mainly provided by the leakage of excess charge through the mitochondrial membrane. It is assumed that the DNICs have the therapeutic potential for treating cardiovascular diseases and for decreasing of chemotherapy-induced cardiotoxicity in cancer survivors.

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Nanoparticles from chitosan and hyaluronic acid were obtained using ionotropic gelation technology. The size of the nanoparticles was investigated using electron microscopy and dynamic light scattering. Nanoparticles were obtained of an optimal size of ∼ 100 nm. A physical association method has been developed of encapsulating nanoparticles with doxorubicin, a well-known antitumor drug, and dinitrosyl iron complex (donor of nitric oxide). The surface potential of nanoparticles was determined by dynamic light scattering. It was shown that HA-DOX: CS {6: 1} nanoparticles were stable and had a potential of -45.6 meV. The localization of nanoparticles in the cancer cells has been studied by confocal and FLIM microscopy. It was found that nanoparticles with doxorubicin are located in the cell near and inside the nucleus. It was shown that the encapsulation of DNIC in the composition of nanoparticles significantly increases the stability of DNIC, prolongs the formation and increases the yield of nitric oxide. A unique nano-system has been created for the delivery of anticancer drugs into the cell.

The effect of synthetic analogues of dinitrosyl mononuclear iron complexes (DNICs) with functional sulfur-containing ligands (NO donors) on the activity of myeloperoxidase (MPO) was studied, and their efficiency was evaluated. It was shown that the enzyme MPO is the molecular target of DNICs. It was found that six DNICs inhibited the activity of MPO and one compound potentiated it. The evaluation of their efficiency showed that two DNICs effectively inhibited the activity of MPO by 50% at IC = 2 × 10 M and IC = 5 × 10 M.