Photosensitizer Chlorin e6 Internalization into Tumor Cells in Phospholipid Nanoparticles Conjugated with Peptide Containing the NGR Sequence
1Institute of Biomedical Chemistry, 10 Pogodinskaya, Moscow, 119221 Russia; *e-mail: firstname.lastname@example.org
2Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency,
1a Pirogovskaya str., Moscow, 119221 Russia
Key words: chlorin e6; phospholipid nanoparticles; HepG2; MCF-7; aminopeptidase N; NGR
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.
The authors thank the peptide engineering laboratory staff, headed by Professor E.F. Kolesanova, in Institute of Biomedical Chemistry, for providing synthesized by them heptaarginine. This work was performed within the framework of the Program for Basic Research of Russia State Academies of Sciences for 2013− 2020.
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