Targeted drug delivery system for doxorubicin based on a specific peptide and phospholipid nanoparticles

   
Kostryukova L.V.1, Tereshkina Y.A.1 , Korotkevich E.I.1, Prozorovsky V.N.1, Torkhovskaya T.I.1, Morozevich G.E.1, Toropygin I.Y.1, Konstantinov M.A.2, Tikhonova E.G.1

1. Institute of Biomedical Chemistry, Moscow, Russia
2. Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Medical University, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20206606464      PubMed Id: 33372904
Year: 2020  Volume: 66  Issue: 6  Pages: 464-468
Doxorubicin is one of the widely known and frequently used chemotherapy drugs for the treatment of various types of cancer, the use of which is difficult due to its high cardiotoxicity. Targeted drug delivery systems are being developed to reduce side effects. One of the promising components as vector molecules (ligands) are NGR-containing peptides that are affinity for the CD13 receptor, which is expressed on the surface of many tumor cells and tumor blood vessels. Previously, a method was developed for preparing a composition of doxorubicin embedded in phospholipid nanoparticles with a targeted fragment in the form of an ultrafine emulsion. The resulting composition was characterized by a small particle size (less than 40 nm) and a high degree of incorporation of doxorubicin (about 93%) into transport nanoparticles. When assessing the penetrating ability and the degree of binding to the surface of fibrosarcoma cells (HT-1080), it was shown that when the composition with the targeted fragment was added to the cells, the level of doxorubicin was almost 2 times higher than that of the liposomal form of doxorubicin, i.e. the drug in the system with the targeted peptide penetrated the cell better. At the same time, on the control line of breast adenocarcinoma cells (MCF-7), which do not express the CD13 receptor on the surface, there was not significant difference in the level of doxorubicin in the cells. The data obtained allow us to draw preliminary conclusions about the prospects of targeted delivery of doxorubicin to tumor cells when using a peptide conjugate containing an NGR motif and the further need for its comprehensive study.
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Keywords: phospholipid nanoparticles, doxorubicin, NGR-containing peptide, cytotoxicity, penetrating ability
Citation:

Kostryukova, L. V., Tereshkina, Y. A., Korotkevich, E. I., Prozorovsky, V. N., Torkhovskaya, T. I., Morozevich, G. E., Toropygin, I. Y., Konstantinov, M. A., Tikhonova, E. G. (2020). Targeted drug delivery system for doxorubicin based on a specific peptide and phospholipid nanoparticles. Biomeditsinskaya khimiya, 66(6), 464-468.
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