Simple procedures for Ta₂O₅ nanoparticle (NP) synthesis and surfactant-free stable hydrosol preparation were developed in order to investigate the colloidal properties, cytotoxicity, and CT contrast performance of uncoated Ta₂O₅ NPs.

Conventional methods for the detection and differentiation of Bacillus cereus group species have drawbacks mostly due to the complexity of genetic discrimination between the Bacillus cereus species. Here, we describe a simple and straightforward assay based on the detected unamplified bacterial 16S rRNA by DNA nanomachine (DNM). The assay uses a universal fluorescent reporter and four all-DNA binding fragments, three of which are responsible for “opening up” the folded rRNA while the fourth stand is responsible for detecting single nucleotide variation (SNV) with high selectivity. Binding of the DNM to 16S rRNA results in the formation of the 10–23 deoxyribozyme catalytic core that cleaves the fluorescent reporter and produces a signal, which is amplified over time due to catalytic turnover. This developed biplex assay enables the detection of B. thuringiensis 16S rRNA at fluorescein and B. mycoides at Cy5 channels with a limit of detection of 30 × 10³ and 35 × 10³ CFU/mL, respectively, after 1.5 h with a hands-on time of ~10 min. The new assay may simplify the analysis of biological RNA samples and might be useful for environmental monitoring as a simple and inexpensive alternative to amplification-based nucleic acid analysis. The DNM proposed here may become an advantageous tool for detecting SNV in clinically significant DNA or RNA samples and can easily differentiate SNV under broadly variable experimental conditions and without prior amplification.

Cancer is still one of the major diseases worldwide. The discovery of new drugs and the improvement of existing ones is one of the areas of priority in the fight against cancer. Dioxadet ([5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol) represents one of the promising 1,3,5-triazine derivatives and has cytostatic activity towards ovarian cancer. In this study, we first report the development of dioxadet-bearing nanomedicines based on block-copolymers of poly(ethylene glycol) monomethyl ether (mPEG) and poly(D,L-lactic acid) (PLA)/poly(ε-caprolactone) (PCL) and then conduct an investigation into their characteristics and properties. The preparation of narrow-sized nanoparticles with a hydrodynamic diameter of 100–120 nm was optimized using a nanoprecipitation approach. Thoughtful optimization of the preparation of nanomedicines was carried out through adjustments to the polymer’s molecular weight, the pH of the aqueous medium used for nanoprecipitation, the initial drug amount in respect to the polymer, and polymer concentration in the organic phase. Under optimized conditions, spherical-shaped nanomedicines with a hydrodynamic diameter of up to 230 nm (PDI < 0.2) containing up to 592 ± 22 μg of dioxadet per mg of polymer nanoparticles were prepared. Study of the drug’s release in a model medium revealed the release up to 64% and 46% of the drug after 8 days for mPEG-b-PLA and mPEG-b-PCL, respectively. Deep analysis of the release mechanisms was carried out with the use of a number of mathematical models. The developed nanoparticles were non-toxic towards both normal (CHO-K1) and cancer (A2780 and SK-OV-3) ovarian cells. A cell cycle study revealed lesser toxicity of nanomedicines towards normal cells and increased toxicity towards cancer cells. The IC₅₀ values determined for dioxadet nanoformulations were in the range of 0.47–4.98 μg/mL for cancer cells, which is close to the free drug’s efficacy (2.60–4.14 μg/mL). The highest cytotoxic effect was found for dioxadet loaded to mPEG-b-PCL nanoparticles.

The development of effective anti-cancer therapeutics remains one of the current pharmaceutical challenges. The joint delivery of chemotherapeutic agents and biopharmaceuticals is a cutting-edge approach to creating therapeutic agents of enhanced efficacy. In this study, amphiphilic polypeptide delivery systems capable of loading both hydrophobic drug and small interfering RNA (siRNA) were developed. The synthesis of amphiphilic polypeptides included two steps: (i) synthesis of poly-αl-lysine by ring-opening polymerization and (ii) its post-polymerization modification with hydrophobic l-amino acid and l-arginine/l-histidine. The obtained polymers were used for the preparation of single and dual delivery systems of PTX and short double-stranded nucleic acid. The obtained double component systems were quite compact and had a hydrodynamic diameter in the range of 90–200 nm depending on the polypeptide. The release of PTX from the formulations was studied, and the release profiles were approximated using a number of mathematical dissolution models to establish the most probable release mechanism. A determination of the cytotoxicity in normal (HEK 293T) and cancer (HeLa and A549) cells revealed the higher toxicity of the polypeptide particles to cancer cells. The separate evaluation of the biological activity of PTX and anti-GFP siRNA formulations testified the inhibitory efficiency of PTX formulations based on all polypeptides (IC₅₀ 4.5–6.2 ng/mL), while gene silencing was effective only for the Tyr-Arg-containing polypeptide (56–70% GFP knockdown).

The rational design of cyclin-dependent protein kinase (CDK) inhibitors presumes the development of approaches for accurate prediction of selectivity and the activity of small molecular weight anticancer drug candidates. Aiming at attenuation of general toxicity of low selectivity compounds, we herein explored the new chemotype of imidazole-4-N-acetamide substituted derivatives of the pan-CDK inhibitor PHA-793887. Newly synthesized compounds 1–4 containing an aliphatic methyl group or aromatic radicals at the periphery of the scaffold were analyzed for the prediction of relative free energies of binding to CDK1, -2, -5, and -9 using a protocol based on non-equilibrium (NEQ) thermodynamics. This methodology allows for the demonstration of a good correlation between the calculated parameters of interaction of 1–4 with individual targets and the values of inhibitory potencies in in vitro kinase assays. We provide evidence in support of NEQ thermodynamics as a time sparing, precise, and productive approach for generating chemical inhibitors of clinically relevant anticancer targets.

The search for new anticancer drugs based on biogenic metals, which have weaker side effects compared to platinum-based drugs, remains an urgent task in medicinal chemistry. Titanocene dichloride, a coordination compound of fully biocompatible titanium, has failed in pre-clinical trials but continues to attract the attention of researchers as a structural framework for the development of new cytotoxic compounds. In this study, a series of titanocene (IV) carboxylate complexes, both new and those known from the literature, was synthesized, and their structures were confirmed by a complex of physicochemical methods and X-ray diffraction analysis (including one previously unknown structure based on perfluorinated benzoic acid). The comprehensive comparison of three approaches for the synthesis of titanocene derivatives known from the literature (the nucleophilic substitution of chloride anions of titanocene dichloride with sodium and silver salts of carboxylic acids as well as the reaction of dimethyltitanocene with carboxylic acids themselves) made it possible to optimize these methods to obtain higher yields of individual target compounds, generalize the advantages and disadvantages of these techniques, and determine the substrate frames of each method. The redox potentials of all obtained titanocene derivatives were determined by cyclic voltammetry. The relationship between the structure of ligands, the reduction potentials of titanocene (IV), and their relative stability in redox processes, as obtained in this work, can be used for the design and synthesis of new effective cytotoxic titanocene complexes. The study of the stability of the carboxylate-containing derivatives of titanocene obtained in the work in aqueous media showed that they were more resistant to hydrolysis than titanocene dichloride. Preliminary tests of the cytotoxicity of the synthesised titanocene dicarboxilates on MCF7 and MCF7-10A cell lines demonstrated an IC50 ≥ 100 μM for all the obtained compounds.