Development of combined schemes for the treatment of oncological diseases is a promising strategy to improve the effectiveness of antitumor therapy. As a result of combination, an additive or synergistic effect at a reduced therapeutic dose of each individual component can be observed. The high potential was recently shown for combination of targeted therapy and photodynamic treatment (PDT). In this work, we studied the therapeutic potential of the combined action of the anticancer targeted toxin and PDT against HER2-positive breast cancer in vitro.

The human breast adenocarcinoma SK-BR-3 cells were sequential treated with recombinant HER2-targeted toxin DARPin-LoPE and then Photodithazine followed by light irradiation and the effect was compared with monotherapeutic options. Photodynamic treatment led to photoinduced cell death with IC₅₀ 0.64 µM and after incubation with the toxin for 48 h IC₅₀ was 2.8 pM. When using two therapeutic agents at IC₅₀ doses, it led to significant increase in the effectiveness; the viability of the combination-treated cell culture did not exceed 10%. To analyze the mode of the drug interaction, we compared the dose-response curves for DARPin-LoPE and Photodithazine at monotherapeutic or combined treatment. The ratio between agents’ concentrations was maintained equal (1:250), which corresponds to the IC₅₀ ratio. The calculated combination index was 0.07 indicating a significant synergistic effect of the agents. The hakf-maximal decrease in the viability of the SK-BR-3 culture was observed at concentrations of the toxin and photosensitizer that are virtually non-toxic to cells when the agents are used separately. We hypothesize that the protein synthesis arrest by DARPin-LoPE toxin is the main cause for sensitization of the cells to the subsequent PDT treatment.

This work was supported by the Russian Science Foundation projects nos. 19-14-00112 (obtaining the recombinant toxin) and 19-74-20168 (studying the efficiency of combination therapy).

Background: Polymeric nanoparticles are a promising substances for the delivery of therapeutics. Among polymeric nanoparticles, PLGA is famous because of its biodegradability, biocompatibility, stability, and sustained drug release. Poly(vinyl alcohol) and poloxamer188 are stabilizers and surfactants which are applied as nanoparticle stabilizers and targeting delivery agents, respectively. The benefits of herbal medicine in palliative therapy have been studied. Cinnamon extract has received a lot of attentions due to its significant properties such as antibacterial, antifungal, antioxidant, and even anti-cancer properties. The aim of this study was to prepare PLGA nanoparticles loaded with cinnamon extract and characterize their physiochemical properties and also their antioxidant and cytotoxicity against the C6 cell line.

Materials and methods: PLGA nanoparticles were prepared by the emulsion solvent evaporation technique. The mean diameter of nanoparticles was assayed using Dynamic Light Scattering, and Scanning Electron Microscopy. Zeta potential was measured as well. Drug loading and encapsulation efficiency were also performed. Antioxidant activity and also cytotoxicity of nanoparticles were assayed by DPPH and MTT, respectively.

Results: the mean diameter of nanoparticles was about 100 nm with the negative zeta potential. Drug loading and encapsulation efficiency were 4.2% and 51% respectively. The release profile of cinnamon extract from PLGA nanoparticles was extended until 5 days. The antioxidant activity of the cinnamon extract was partially preserved in nanoparticles and also the anticancer property of nanoparticles was confirmed via MTT assay.

Runt-related transcription factor 1 gene (RUNX1), also known as acute myeloid leukemia 1 protein (AML1), plays a critical role in the pathogenesis of AML. One of leukemia's most frequently mutated genes is RUNX1/AML1, which is related to a poor prognosis in AML. Researchers and clinicians can design personalized medicines and enhance diagnosis by identifying biomarkers linked to genetic mutations. In the current study, we used TCGA-Acute Myeloid Leukemia (AML) cohort's genomic and transcriptome data. We analyzed RUNX1 mutated AML patients to non-mutated patients using an integrated, multi-omics, multi-database analysis of exome and transcriptomics data. The mutation landscape of several genes, including RUNX1 mutations, was revealed by TCGA-AML data from multi-center high-throughput exome sequencing. Finally, we identified the gene signature associated with RUNX1 mutations, including prognostic genes that significantly impacted the overexpression of the RUNX1 pathway in RUNX1 mutated AML patients. Our findings may help diagnose AML patients with RUNX1 mutations early.