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

Autor: Lyubov V. Kostryukova, Yulia A. Tereshkina, Elena G. Tikhonova, Yulia Yu. Khudoklinova, Daria V. Bobrova, Alisa M. Gisina, Galina E. Morozevich, Veronica V. Pronina, Tatiana V. Bulko, Victoria V. Shumyantseva
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nanomaterials, Vol 13, Iss 15, p 2229 (2023)
Druh dokumentu: article
ISSN: 2079-4991
DOI: 10.3390/nano13152229
Popis: 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.
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