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The interactions of dsDNA with new targeted drug delivery derivatives of doxorubicin (DOX), such as DOX embedded into phospholipid nanoparticles (NPhs) and DOX with the NGR targeted peptide-modified NPhs were studied electrochemically by differential pulse voltammetry technique. Screen-printed electrodes (SPEs), modified with stable fine dispersions of carbon nanotubes (CNTs), were used for quantitative electrochemical investigations of direct electrochemical oxidation of guanine, adenine, and thymine heterocyclic bases of dsDNA, and their changes in the presence of DOX nanoderivatives. Analysing the shifts of peak potentials of nucleobases in the presence of drug, we have shown that the doxorubicin with NGR targeted peptide changed the mode of interaction in DNA–drug complexes from intercalative to electrostatic. Binding constants (Kb) of DNA–drug complexes were calculated in accordance with adenine, guanine, and thymine oxidation signals. Based on our experiments, we have proven that the surface modification of a drug delivery system with NGR targeted peptide dramatically changed the mechanism of interaction of drug with genetic material. DNA-mediated drug toxicity was calculated based on the concentration-dependent "response" of heterocyclic nucleobases on drug influence. DOX, DOX-loaded phospholipid nanoparticles (NPhs), and DOX with NGR addressed peptide-modified NPhs were moderately toxic in the concentration range of 0.5–290 µM. [ABSTRACT FROM AUTHOR]

In the present study, the electrochemical behavior of antiviral drug umifenovir (Umi) and umifenovir encapsulated in phospholipids micelles (nanosome/umifenovir, NUmi) were investigated for the first time on screen-printed electrodes modified by carbon nanotubes. We have shown that Umi can be electro oxidized around the potential of +0.4 V in the concentration range of 50–500 µM (R2 = 0.992). Non-overlapping signatures of DNA and umifenovir (10–150 µM) permit to register interaction between umifenovir (or umifenovir encapsulated in phospholipids micelles), purine, and pyrimidine heterocyclic bases of DNA separately. The type of interaction is most likely via electrostatic interactions and groove binding in drug-DNA formed complex, as was revealed based on the values of binding constants Kb and the cathodic shifts of oxidation potentials for heterocyclic bases with increasing Umi or NUmi concentration. The negative values of Gibbs free energy (ΔG) for all nucleobases confirm the process spontaneity. This study is the first one presenting the effect of antiviral drug umifenovir and umifenovir encapsulated in phospholipids micelles on dsDNA as a target of pharmacogenomics. [ABSTRACT FROM AUTHOR]