Effect of an NGR Peptide on the Efficacy of the Doxorubicin Phospholipid Delivery System

Abstract

This study is a continuation of an investigation into the effect of a targeted component, a peptide with an NGR, on the properties of the previously developed doxorubicin phospholipid delivery system. The NGR peptide has an affinity for aminopeptidase N (known as the CD13 marker on the membrane surface of tumor cells) and has been extensively used to target drug delivery systems. This article presents the results of a study investigating the physical properties of the phospholipid composition with and without the peptide chain: particle size, zeta potential, stability in fluids, and dependence of doxorubicin release from nanoparticles at different pH levels (5.0, 6.5, 7.4). The cytotoxic effect of the compositions has also been shown to depend on the dose of the drug used for incubation, the presence of the targeted component in the composition, and the time of incubation time of the substances. There was a significant difference in the cytotoxic effect on HT-1080 (CD13-positive) and MCF-7 (CD13-negative) cells. Cell death pathway analysis has shown that death occurred mainly by apoptosis. We also present data on the effect of doxorubicin embedded in phospholipid nanoparticles with the targeted peptide on DNA assessed by differential pulse voltammetry, the mechanism of action being electrostatic interactions. The interactions of native dsDNA with doxorubicin encapsulated in phospholipid nanoparticles with the targeted peptide were studied electrochemically by differential pulse voltammetry. Here, we have highlighted that the targeted peptide in the doxorubicin composition moved specific interaction of the drug with dsDNA from intercalative mode to electrostatic interactions.

Pharmacogenomic Studies of Antiviral Drug Favipiravir

“…These types of DNA or RNA possess diagnostic relevance as specific markers of diseases and play a role in organism defense at the transcription/translation regulation level [ 72 , 74 , 75 , 76 , 77 ]. The detection of DNA/drug complex formation and study of the mode of interactions are the main points of pharmacogenomics [ 36 , 78 , 79 , 80 , 81 , 82 , 83 ].…”

“…It is a well-known viewpoint that the positive shift of the oxidation of heterocyclic bases peak potentials is typical for the intercalative hydrophobic mode of drugs during binding to DNA. In contrast, the negative shift is representative of the binding modes such as electrostatic interaction or groove binding [ 35 , 36 , 37 , 38 , 80 , 83 ]. In order to determine the optimum time for FAV/dsDNA complex formation, we compare the intensities of nucleic bases´ oxidation signals after the interaction of dsDNA with 500 μM in time intervals of 5 and 40 min.…”

“…To estimate the mode of interaction, the binding constants for the complex FAV/dsDNA were calculated based on the values of the oxidation current of nucleobases before and after the interaction of DNA with the drug, in accordance with an earlier-published approach for the determination of this parameter [ 54 , 72 ] ( Figure S2 ). Intercalation-based interactions are characterized by high Kb values, usually 10 4 –10 6 M −1 , while lower Kb values imply a rather weaker interaction, such as groove or electrostatic interactions [ 36 , 38 , 78 , 79 , 80 ]. The structure of FAV permits the formation of two hydrogen bonds with adenine residue.…”

“…These types of DNA or RNA possess diagnostic relevance as specific markers of diseases and play a role in organism defense at the transcription/translation regulation level [72,[74][75][76][77]. The detection of DNA/drug complex formation and study of the mode of interactions are the main points of pharmacogenomics [36,[78][79][80][81][82][83]. Electrochemical analysis of dsDNA based on direct electrochemical oxidation of guanine, adenine and thymine residues [82] was used.…”