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

Abstract

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.

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

“…Doxorubicin (DOX) is an antineoplastic antibiotic with wide pharmacological activity [ 2 , 3 , 7 , 24 , 31 , 34 , 35 , 36 , 37 , 38 ]. Analysis of DOX levels is an important task for the determination of this medication in body fluids for the individualization of drug dosage, and for the investigation and evaluation of the mechanism of drug–biomolecule(s) interactions [ 12 , 39 , 40 , 41 ].…”

“…The NGR peptide has affinity for aminopeptidase N (known as the CD13 marker on the membrane surface of tumor cells). It was shown that the new doxorubicin derivative with NGR peptide (NPh-DOX-NGR) is able to penetrate and internalize to a greater extent in HT-1080 (CD13-positive) cells [ 24 ]. NGR peptide did not reduce anticancer activity of DOX [ 56 , 57 ].…”

“…Liposomes and lipid nanocarriers are often employed in drug delivery due to precise targeting of different tissues [ 8 , 24 ]. The developed compositions of DOX, a targeted CD13-directed peptide, have shown their effectiveness in vitro [ 24 ].…”

Targeting Engineered Nanoparticles for Breast Cancer Therapy

“…Several methods and tools are presently accessible to shield NPs for the active targeting of BC cells. Previously, monoclonal antibodies were employed to target epitopes on the cell surface; however, the widespread screening of peptide and aptamer archives has significantly extended the number of ligands available for targeted BC therapy [177]. Various ligands are presently employed, viz., antibodies, peptides, aptamers, oligosaccharides, and small molecules, and can precisely identify and attach to an overexpressed target on the surface of the cell [76,175,176,178].…”

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

“…The inclusion of Dox in phospholipid nanoparticles contributed to its accumulation in the tumor and led to an increase in its specific activity. In subsequent experiments, the resulting Dox phospholipid composition was constructed using a targeted NGR peptide (NPh-Dox-NGR) [32]. This work is a comprehensive study of the physical properties of the Dox phospholipid composition with and without the To increase bioavailability and reduce side effects, NPs are modified with various targeted molecules: peptides [14][15][16], aptamers [17][18][19], small molecules [20][21][22], and antibodies [23,24].…”