Abstract
Cytotoxic and photoinduced activity of chlorine e6 (Ce6) in phospholipid nanoparticles containing specific tumor targeting and cell-penetrating peptides was studied in vitro using human fibrosarcoma cells НТ-1080. It was shown, that addition of the cell-penetrating heptaarginine peptide (R7) alone or in combination with the peptide containing specific targeting motif NGR (Asn-Gly-Arg) resulted in a 3-fold increase of Ce6 photoinduced activity as compared with that in nanoparticles without peptides (the IC50 values were 0.7 µg/mL and 2.1 µg/mL, respectively). A weak effect of NGR alone (less than 20%; IC50 1.7 µg/mL) and the lack of its effect in addition to R7 (IC50 0.7 µg/mL) suggest a greater importance of Ce6 penetration into cells rather than NGR-mediated targeting. The effect of inclusion of both peptides on the total cytotoxicity of Ce6 was minimal (10−16 times less than on the specific photoinduced activity). The results obtained in this study together with earlier shown effects on improvement of the pharmacokinetics of Ce6 in vivo after its inclusion into phospholipid nanoparticles indicate the prospects of using the obtained phospholipid nanoparticles system for photodynamic therapy.
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ACKNOWLEDGMENTS
The authors are grateful to Professor E.F. Kolesanova and her colleagues at the Laboratory of Peptide Engineering (Institute of Biomedical Chemistry), for providing heptaarginine (R7) the the Senior Researcher of the Laboratory of Protein Biosynthesis, Dr G.E. Morozevich for her help in working with cell cultures.
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This work was carried out in the framework of the Program of fundamental scientific research of state academies of sciences for 2013−2020.
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Translated by A. Medvedev
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Kostryukova, L.V., Plyutinskaya, A.D., Pankratov, A.A. et al. Chlorine e6 in Phospholipid Nanoparticles with Specific Targeting and Penetrating Peptides as Prospective Composition for Photodynamic Therapy of Malignant Neoplasms. Biochem. Moscow Suppl. Ser. B 14, 174–179 (2020). https://doi.org/10.1134/S1990750820020080
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DOI: https://doi.org/10.1134/S1990750820020080