Lipid Status of A2780 Ovarian Cancer Cells after Treatment with Ruthenium Complex Modified with Carbon Dot Nanocarriers: A Multimodal SR-FTIR Spectroscopy and MALDI TOF Mass Spectrometry Study

SIMPLE SUMMARY: Developing new anticancer medicaments is focused on inducing controlled elimination of tumor tissue without severe side effects. It is essential to enable the medicament to reach the target molecule without provoking the immune response too early. The first cellular changes might occur already at the level of the cell membrane, composed mainly of lipids. Therefore, we used spectroscopic techniques to study the interaction of potential metallodrug [Ru(η(5)-C(5)H(5))(PPh(3))(2)CN] (RuCN) with lipids of A2780 ovarian cancer cells and investigated if these changes are affected by the presence of drug carriers (carbon dots (CDs) and nitrogen-doped carbon dots (N-CDs)). Our results showed that CDs and N-CDs prevent lysis and moderate oxidative stress of lipids caused by metallodrug, still keeping the antitumor activity and potential to penetrate through the lipid bilayer. Therefore, Ru drug loading to carriers balances the anticancer efficiency and leads to better anticancer outcomes by reducing the oxidative stress that has been linked to cancer progression. ABSTRACT: In the last decade, targeting membrane lipids in cancer cells has been a promising approach that deserves attention in the field of anticancer drug development. To get a comprehensive understanding of the effect of the drug [Ru(η(5)-Cp)(PPh(3))(2)CN] (RuCN) on cell lipidic components, we combine complementary analytical approaches, matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI TOF MS) and synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy. Techniques are used for screening the effect of potential metallodrug, RuCN, without and with drug carriers (carbon dots (CDs) and nitrogen-doped carbon dots (N-CDs)) on the lipids of the human ovarian cancer cell line A2780. MALDI TOF MS results revealed that the lysis of ovarian cancer membrane lipids is promoted by RuCN and not by drug carriers (CDs and N-CDs). Furthermore, SR-FTIR results strongly suggested that the phospholipids of cancer cells undergo oxidative stress after the treatment with RuCN that was accompanied by the disordering of the fatty acid chains. On the other hand, using (N-)CDs as RuCN nanocarriers prevented the oxidative stress caused by RuCN but did not prevent the disordering of the fatty acid chain packing. Finally, we demonstrated that RuCN and RuCN/(N-)CDs alter the hydration of the membrane surface in the membrane–water interface region.