Abstract
Simple SummaryDeveloping 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(η5-C5H5)(PPh3)2CN] (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.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(η5-Cp)(PPh3)2CN] (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.
Highlights
The cell membrane is a complex and highly diverse cellular component, mainly composed of a large variety of different lipids [1]
While the MALDI TOF MS was used to track the effects of drug molecules on the isolated lipids and identify them, FTIR spectroscopy tracked specific chemical events after the treatments in the lipid region of all individual living cancer cells
The first process appears to be most affected by the surface charge, size, and lipophilicity of the NPs; we examined these properties for RuCN, carbon dots (CDs), and N-doped carbon dots (N-CDs) used in our study, and the results
Summary
The cell membrane is a complex and highly diverse cellular component, mainly composed of a large variety of different lipids [1]. Any drug must interact first with the membrane to cross it and reach its intracellular target(s). For this reason, the efficiency of drugs’ interaction with the constituents of the membrane, primarily membrane lipids, is one of the pharmacological features playing a crucial role in their biological activity [2]. The role of membrane lipids in regulating numerous cellular functions has led to the emergence of cell lipids as an alternative molecular drug target. The interaction of drug molecules with the lipid membrane leads to changes in the physicochemical properties, pharmacological activity, and bioavailability of the drug. This interaction could lead to changes in lipid structure and membrane integrity [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
