Nešić Maja D, Dučić Tanja, Algarra Manuel, Popović Iva, Stepić Milutin, Gonçalves Mara, Petković Marijana
Center for Light-Based Research and Technologies COHERENCE, Department of Atomic Physics, Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
ALBA-CELLS Synchrotron, MIRAS Beamline, 08290 Cerdanyola del Vallès, Spain.
Cancers (Basel). 2022 Feb 24;14(5):1182. doi: 10.3390/cancers14051182.
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-Cp)(PPh)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.
在过去十年中,靶向癌细胞中的膜脂一直是一种很有前景的方法,值得在抗癌药物研发领域予以关注。为全面了解药物[Ru(η-Cp)(PPh)CN](RuCN)对细胞脂质成分的影响,我们结合了互补的分析方法,即基质辅助激光解吸电离飞行时间质谱(MALDI TOF MS)和基于同步辐射的傅里叶变换红外(SR-FTIR)光谱。这些技术用于筛选潜在金属药物RuCN在有无药物载体(碳点(CDs)和氮掺杂碳点(N-CDs))情况下对人卵巢癌细胞系A2780脂质的影响。MALDI TOF MS结果显示,RuCN可促进卵巢癌膜脂的裂解,而药物载体(CDs和N-CDs)则无此作用。此外,SR-FTIR结果有力地表明,RuCN处理后癌细胞的磷脂会经历氧化应激,同时伴随着脂肪酸链的无序化。另一方面,使用(N-)CDs作为RuCN纳米载体可防止RuCN引起的氧化应激,但不能防止脂肪酸链堆积的无序化。最后,我们证明RuCN和RuCN/(N-)CDs会改变膜-水界面区域膜表面的水合作用。