Controlling the Quality of Nanodrugs According to Their New Property-Radiothermal Emission.

Previous studies have shown that complexly shaped nanoparticles (NPs) have their intrinsic radiothermal emission in the millimeter range. This article presents a method for controlling the quality of nanodrugs-immunobiological preparations (IBPs)-based on the detection of their intrinsic radiothermal emissions. The emissivity of interferon (IFN) medicals, determined without opening the primary package, is as follows (µW/m2): IFN-α2b-80 ± 9 (105 IU per package), IFN-ß1a-40 ± 5 (24 × 106 IU per package), IFN-γ-30 ± 4 (105 IU per package). The emissivity of virus-like particles (VLP), determined using vaccines Gam-VLP-multivac (120 µg) in an injection bottle (crimp cap vials), was as follows: 12 ± 1 µW/m2, Gam-VLP-rota vaccines-9 ± 1 µW/m2. This study shows the reproducibility of emissivity over the course of a year, subject to the storage conditions of the immunobiological products. It has been shown that accelerated aging and a longer shelf life are accompanied by the coagulation of active NPs, and lead to a manyfold drop in emissivity. The dependence of radiothermal emission on temperature has a complex, non-monotonic nature. The emission intensity depends on the form of dosage, but remains within the order of magnitude for IFN-α2b for intranasal aqueous solution, ointments, and suppositories. The possibility of the remote quantitative control of the first phases of the immune response (increased synthesis of IFNs) to the intranasal administration of VLP vaccines has been demonstrated in experimental animals.

Inhibitor of polyamine catabolism MDL72.527 restores the sensitivity to doxorubicin of monocytic leukemia Thp-1 cells infected with human cytomegalovirus.

Leukemic cells from different patients exhibit different sensitivity to anticancer drugs including doxorubicin (DOX). Resistance to chemotherapy decreases efficacy of the treatment and promotes cancer recurrence and metastases. One of the approaches to overcome drug resistance includes E2F1-mediated regulation of the р73 protein that belongs to the р53 family. Its ΔNp73 isoform exhibits pro-oncogenic effects, and TAp73 - anti-oncogenic effects. Human cytomegalovirus (HCMV), often found in tumors, suppresses pro-apoptotic pathways and E2F1/p73 in particular. The activity of E2F1 and p73 transcription factors is linked to metabolism of biogenic polyamines. Therefore, it could be suggested that compounds that target polyamine-metabolizing enzymes can sensitize HCMV-infected hematological malignancies to doxorubicin. Here we report that HCMV infection of ТНР-1 monocytic leukemic cells considerably elevates E2F1 levels and shifts the balance between the р73 isoforms towards ΔNp73 leading to survival of DOX-treated leukemic cells. In contrast, MDL72.527, an inhibitor of polyamine catabolism, decreases ΔNp73/ТАр73 ratio and thus restores sensitivity of the cells to DOX. Our findings indicate the combination of doxorubicin and MDL72.527 may present a novel strategy for therapy of leukemia in patients with and without HCMV infection.