Photosensitizer Chlorin e6 Internalization into Tumor Cells in Phospholipid Nanoparticles Conjugated with Peptide Containing the NGR Sequence

  • V.N. Prozorovskiy Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • L.V. Kostryukova Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • E.I. Korotkevich Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • T.I. Torkhovskaya Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 1a Pirogovskaya str., Moscow, 119221 Russia
  • G.E. Morozevich Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • E.G. Tikhonova Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • O.M. Ipatova Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
Keywords: NGR; aminopeptidase N; MCF-7; HepG2; phospholipid nanoparticles; chlorin e6

Abstract

The possibility of increased internalization of the photosensitizer chlorin e6 in tumor cells was investigatedusing soy phosphatidylcholine nanoparticles 20-30 nm with or without attached peptide containing Asn-Gly-Arg (NGR) motif was studied. This amino acid sequence exhibits affinity to aminopeptidase N (CD13), wich is overexpressed in a number of tumor cells and vessels. Nanoparticles with chlorin e6 were prepared with added of distearoylphosphatidylcholine (DSPE) conjugated through PEG with a hexapeptide containing the NGR sequence, and then were incubated with tumor cells НерG2 and MCF-7. Chlorin e6 accumulation in СD13-negative cells (MCF-7) did not depend on the presence of peptide NGR in nanoparticles. However, for НерG2 cells a twofold increase of chlorine e6 internalization was observed as compared with the same particles without NGR. Differences in the response of these two cell lines, differed in expression of aminopeptidase N (APN), suggest the possibility of this protein using for targeted delivery. The prospectivity of usage of phospholipids nanoparticles conjugated with targeting peptide for photodynamic therapy is discussed, taking into account possible variation of APN expression, inherent for many solid tumors.

References

  1. Krasnovskiy A.A. (2015) Singlet oxygen and primary mechanisms of photodynamic therapy in: Fundamental Sciences for medicine (Eds. A.I.Grigoryev, Yu.A.Vladimirov) Max Press, Моscow, v. 1, p. 173-217.

  2. Chan Thi Hai Yen, Ramenskaya G.V., Oborotova N.A. (2009) Photosensitizers of chlorine range in PhDT of tumors. Russian Journal of Biotherapy, 8(4), 99-104.

  3. Yuan A., Yang B., Wu J., Hu Y., Ming X. (2015) Dendritic nanoconjugates of photosensitizer for targeted photodynamic therapy. Acta Biomater., 21, 63-73. DOI

  4. Kim S.K., Lee J.M., Oh K.T., Lee E.S. (2017) Extremely small-sized globular poly(ethylene glycol)-cyclic RGD conjugates targeting integrin αvβ3 in tumor cells. Int. J. Pharm., 528(1-2), 1-7. DOI

  5. Moret F., Scheglmann D., Reddi E. (2013) Folate-targeted PEGylated liposomes improve the selectivity of PDT with meta-tetra(hydroxyphenyl)chlorin (m-THPC). Photochem. Photobiol. Sci., 12(5), 823-834. DOI

  6. Kim K.S., Kim J., Kim D.H., Hwang H.S., Na K. (2018) Multifunctional trastuzumab-chlorin e6 conjugate for the treatment of HER2-positive human breast cancer. Biomater. Sci., 6(5), 1217-1226. DOI

  7. Wickstrom M., Larsson R., Nygren P., Gullbo J. (2011) Aminopeptidase N (CD13) as a target for cancer chemotherapy. Cancer Sci.; 102, 501-508. DOI

  8. Schreiber C.L., Smith B.D. (2018) Molecular Imaging of Aminopeptidase N in Cancer and Angiogenesis. Contrast Media Mol. Imaging., 2018:5315172. DOI

  9. Prozorovskiy V.N., Torkhovskaya T.I., Kostryukova L.V., Ipatova O.M. (2018) Specific peptides usage for targeted delivery of nanoparticles with antitumor drugs. Russian Journal of Biopharmaceutical, 10(4), 3-18.

  10. Kostryukova L.V., Prozorovskiy V.N., Medvedeva N.V., Ipatova O.M. (2018) Comparison of a new nanoform of the photosensitizer chlorin e6, based on plant phospholipids, with its free form FEBS Open Bio., 8(2), 201-210. DOI

  11. Yang Y., Yang Y., Xie X., Cai X., Zhang H., Gong.W., Wang Z., Mei X. (2014) PEGylated liposomes with NGR ligand and heat-activable cell-penetrating peptide-doxorubicin conjugate for tumor-specific therapy. Biomaterials, 35(14), 4368-4381. DOI

  12. Sheldon K., Liu D., Ferguson J., Gariépy J. (1995) Loligomers: design of de novo peptide-based intracellular vehicles. Proc. Natl. Acad. Sci. U S A. 92(6), 2056-2060. DOI

  13. Hou L., Zhao X., Wang P., Ning Q., Meng M., Liu C. (2013) Antitumor activity of antimicrobial peptides containing CisoDGRC in CD13 negative breast cancer cells. PLoS One, 8(1), e53491. DOI

  14. Isbilen O., Rizaner N., Volkan E. (2018) Anti-proliferative and cytotoxic activities of Allium autumnale P. H. Davis (Amaryllidaceae) on human breast cancer cell lines MCF-7 and MDA- MB-231. BMC Complement. Altern. Med., 18(1), 30. DOI

  15. Huang Y., Cheng Q., Jin X., Ji J.L., Guo S., Zheng S., Wang X., Cao H., Gao S., Liang X.J., Du Q., Liang Z. (2016) Systemic and tumor-targeted delivery of siRNA by cyclic NGR and isoDGR motif-containing peptides. Biomater. Sci., 4(3):494-510. DOI

Published
2018-11-15
Section
Experimental Research