Electrochemical Studies of the Interaction of Phospholipid Nanoparticles with dsDNA

Abstract

The effect of phospholipid nanoparticles with different contents of phosphatidylcholine (PhNP80 and PhNP100) on dsDNA was studied by means of the electrochemical method. Changes in the electrochemical behavior of heterocyclic bases guanine, adenine and thymine in the range of potentials of 0.2–1.2 V in the presence of PhNPs were used for the assessment of the binding mechanism of the ligand–DNA interaction. Comparative analysis of the effect of PhNPs with different contents of phosphatidylcholine showed a more pronounced effect on the dsDNA of the PhNP100 nanosystem. From the obtained experimental data on the decrease in the amplitude of the nucleobases' electrochemical oxidation currents, the electrochemical coefficient of the toxic effect was calculated as the ratio of the electrooxidation currents of dsDNA and dsDNA in the presence of phospholipid nanoparticles. PhNP80/100 (up to 11.4 mg/mL) does not influence dsDNA, PhNP80/100 (14.3–28.5 mg/mL) has a moderate toxic effect on dsDNA, PhNP80/100 at concentrations above 28.5 mg/mL already have a toxic effect, significantly reducing the maximum amplitude of the heterocyclic bases’ electrochemical oxidation current. Peak potentials of electrochemical oxidation of nucleobases did not shift in the presence of PhNP80 and PhNP100 (in the concentration range of 2.3–42.2 mg/mL), which could be possible through a groove-binding mode of phospholipid nanoparticle interaction with dsDNA.

Pharmacogenomic Studies of Antiviral Drug Favipiravir

“…Earlier, we showed that electrochemical oxidation of dsDNA was successfully achieved on SPE/CNT after dsDNA immobilization by physical entrapment/absorption on the surface of the modified electrodes. Modification of SPEswith CNT stabilized with carboxymethylcellulose (SPE/CNT) allowed the registering of electrochemical oxidation of guanine, adenine and thymine in the immobilized dsDNA [ 40 , 41 , 71 ]. Adding nanosized titanium (IV) oxide TiO 2 improved the sensitivity of electrodes for the registration of dsDNA ( Figure 4 a,b), as in the case of protein registration [ 43 ].…”

“…DPV of the first (black line) and second (red line) scan of dsDNA (1.5 mg/mL) on SPE/CNT/TiO 2 demonstrated the irreversible nature of the electrochemical process and fouling of the electrode by means of DNA or FAV oxidation products ( Figure 4 c) [ 71 , 72 ]. Based on this observation, we used SPEs only for single measurements.…”

“…FAV itself demonstrated a DPV oxidation signal at around + 0.96 ÷+1 V, in the region of non-overlapping potentials with nucleobases oxidation potentials. Therefore, the investigation of binding of FAV with dsDNA via electrochemical methods was more effective in comparison with the spectrophotometric technique by means of the observation of changes DPV of the first (black line) and second (red line) scan of dsDNA (1.5 mg/mL) on SPE/CNT/TiO2 demonstrated the irreversible nature of the electrochemical process and fouling of the electrode by means of DNA or FAV oxidation products (Figure 4c) [71,72]. Based on this observation, we used SPEs only for single measurements.…”

Interaction of Doxorubicin Embedded into Phospholipid Nanoparticles and Targeted Peptide-Modified Phospholipid Nanoparticles with DNA

“…Differential pulse voltammetry (DPV) possesses high sensitivity, which permits to register heterocyclic bases separately for the detailed study of drug–DNA interactions ( Scheme 3 ). Intensive research was carried out in recent years to study the mechanisms of complex formation of the DNA–drug, such as, for example, rifampicin and nanosome/rifampicin (rifampicin embedded into lipid nanoparticles) [ 27 ], abiraterone acetate [ 28 ], and phospholipid nanoparticles with different contents of phosphatidylcholine [ 29 ]. There are also extensive studies in this area, in the form of review articles [ 12 , 30 , 31 , 32 ], as we have cited.…”

“…The aim of this study is to discover the effects of DOX, or DOX as nanoformulated forms (DOX-loaded NPhs and DOX with the NGR targeted peptide), onto DNA as a model molecule in pharmacogenomics. To assess the mechanism of interaction of medications with DNA, we used electrochemical techniques, which possess high sensitivity, selectivity, and registration of a concentration-dependent “response” of heterocyclic nucleobases on drug influence [ 12 , 21 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”