1. Chlorin e6 embedded in phospholipid nanoparticles equipped with specific peptides: Interaction with tumor cells with different aminopeptidase N expression.
- Author
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Torkhovskaya TI, Kostryukova LV, Tereshkina YA, Tikhonova EG, Morozevich GE, Plutinskaya AD, Lupatov AY, and Pankratov AA
- Subjects
- Breast Neoplasms enzymology, Breast Neoplasms pathology, Carcinoma, Hepatocellular enzymology, Carcinoma, Hepatocellular pathology, Cell Survival drug effects, Cell-Penetrating Peptides chemistry, Chlorophyllides, Drug Compounding, Hep G2 Cells, Humans, Liver Neoplasms enzymology, Liver Neoplasms physiopathology, MCF-7 Cells, Oligopeptides chemistry, Oligopeptides metabolism, Photosensitizing Agents chemistry, Photosensitizing Agents metabolism, Porphyrins chemistry, Porphyrins metabolism, Breast Neoplasms drug therapy, CD13 Antigens metabolism, Carcinoma, Hepatocellular drug therapy, Cell-Penetrating Peptides metabolism, Drug Carriers, Liver Neoplasms drug therapy, Nanoparticles, Phospholipids chemistry, Photochemotherapy, Photosensitizing Agents pharmacology, Porphyrins pharmacology
- Abstract
A promising direction in Biopharmaceuticals is the development of specific peptide-based systems to improve drug delivery. This approach may increase tumor specificity and drug penetration into the target cell. Similar systems have been designed for several antitumor drugs. However, for photodynamic therapy drugs, such studies are not yet enough. Previously, we have developed a method of inclusion of chlorin e6 (Ce6), a photosensitizer used in photodynamic therapy, in phospholipid nanoparticles with a diameter of up to 30 nm, and reported an increase in its effectiveness in the experiments in vivo. In this work, we propose to modify a previously developed delivery system for Ce6 by the addition of cell-penetrating (R7) and/or targeting NGR peptides. The interaction of the compositions developed with HepG2 and MCF-7 tumor cells is shown. The expression of CD13 protein with affinity to NGR on the surface of these cells has been studied using flow cytometry. The expression of this protein on the HepG2 cells and its absence on MCF-7 was demonstrated. After incubation of tumor cells with the resulting Ce6 compositions, we evaluated the cellular accumulation, photoinduced, and dark cytotoxicity of the drugs. After irradiation, the highest level of cytotoxicity was observed when R7 peptide was added to the system, either alone or in combination with NGR. In addition to R7, the NGR-motif peptide increased the internalization of Ce6 in HepG2 cells without affecting its photodynamic activity. In this work we also discuss possible mechanisms of action of the cell-penetrating peptide when attached to phospholipid nanoparticles., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2021
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