The influence of doxorubicin incorporated in phospholipid drug delivery nanosystem on HEPG2 cells proteome

Kuznetzova K.G.1, Kazlas E.V.1, Torkhovskaya T.I.1 , Karalkin P.A.1, Vachrushev I.V.1, Zakharova T.S.1, Sanzhakov M.A.1, Moshkovskiy S.A.1, Ipatova O.M.1

1. Institute of Biomedical Chemistry, Moscow, Russia
DOI: 10.18097/PBMC20156103343      PubMed Id: 26215411
Year: 2015  Volume: 61  Issue: 3  Pages: 343-349
A phospholipid drug delivery nanosystem with particle size up to 30 nm elaborated at the Institute of Biomedical Chemistry has been used earlier for incorporation of doxorubicin (Doxolip). This system demonstrated higher antitumor effect in vivo as compared with free doxorubicin. In this study the effect of this nanosystem containing doxorubicin on HepG2 cell proteome has been investigated. Cells were incubated in a medium containing phospholipid nanoparticles (0.5 mg/ml doxorubicin, 10 mg/mL phosphatidylcholine). After incubation for 48 h their survival represented 10% as compared with untreated cells. Cell proteins were analyzed by quantitative two-dimensional gel electrophoresis followed by identification of differentially expressed proteins with MALDI-TOF mass spectrometry. The phospholipid transport nanosystem itself insignificantly influenced the cell proteome thus confirming previous data on its safety. Doxorubicin, as both free substance and Doxolip (i.e. included into phospholipid nanoparticles) induced changes in expression of 28 proteins. Among these proteins only four of them demonstrated different in response to the effect of the free drug substance and Doxolip. Doxolip exhibited a more pronounced effect on expression of certain proteins; the latter indirectly implies increased penetration of the drug substance (included into nanoparticles) into the tumor cells. Increased antitumor activity of doxorubicin included into phospholipid nanoparticles may be associated with more active increase of specific protein expression.
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Keywords: phospholipid nanoparticles, proteome, doxorubicin, HepG2 cells, MALDI-TOF mass spectrometry

Kuznetzova, K. G., Kazlas, E. V., Torkhovskaya, T. I., Karalkin, P. A., Vachrushev, I. V., Zakharova, T. S., Sanzhakov, M. A., Moshkovskiy, S. A., Ipatova, O. M. (2015). The influence of doxorubicin incorporated in phospholipid drug delivery nanosystem on HEPG2 cells proteome. Biomeditsinskaya Khimiya, 61(3), 343-349.
This paper is also available as the English translation: 10.1134/S1990750814010090
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