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

Abstract

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.

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 ].…”

“…Based on this observation, we used SPEs only for single measurements. This regimen is typical for the irreversible electrochemical process [ 40 , 41 , 73 ].…”

“…The influence of FAV was also represented as the DNA-mediated electrochemical coefficient of toxicity using Equation (2): S = (Ss/Sb) × 100% where Sb and Ss are nucleobase oxidation signals before and after interaction of the FAV with dsDNA, respectively [ 40 , 41 , 84 ]. We used this criterion such that if a drug does not have a toxic effect, S is higher than 85%; it has a moderate toxic effect if the S parameter is between 50 and 85%, and has a toxic effect if S is below 50% [ 83 ].…”

“…The next focus of our experiments will be the investigation of the pharmacogenomic properties of favipiravir in the process of drug/DNA complex formation. Electrochemistry, as a modern and sensitive platform for the analysis of drug/DNA interactions, possesses remarkable advantages, such as miniaturization, high sensitivity and broad potential window permitting registration of the drug itself and the DNA response as oxidation signals of nucleic bases [ 35 , 36 , 37 , 38 , 41 , 42 , 81 , 83 , 84 ]. This study utilizes single-use electrodes (SPE/CNT/TiO 2 /DNA) as sensing elements for the investigation of the antiviral drug favipiravir’s interaction with dsDNA.…”

“…Linear plots for 1/(I 0 − I) depending on 1/[FAV] were used for the calculation of the binding constant Kb [ 40 , 41 ] in accordance with the following equation: Kb ≈ (I 0 − I)/(I 0 × ([FAV] − (I 0 − I)).…”