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Interaction of liposome-encapsulated cisplatin with biomolecules

JBIC Journal of Biological Inorganic Chemistry volume 17, pages 899–910 (2012)Cite this article

Abstract

We prepared liposomes by hydrating 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid with aqueous solutions of three “probe” molecules—cis-diamminedichloroplatinum(II) (cis-[PtII(NH3)2Cl2], cisplatin), guanosine 5′-monophosphate (5′-GMP), and 9-ethylguanine (9-EtG)—in phosphate-buffered saline as well as N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid buffer. The positively charged hydrolysis product of cisplatin, [PtII(NH3)2Cl(H2O)]+, is in the inner core of the liposomes and negatively charged 5′-GMP embeds in the lipid bilayer of liposomes. In the presence of cisplatin, the size of the liposomes remains unchanged, and for 5′-GMP-embedded liposomes the size increases significantly compared with that of empty or control liposomes. In contrast, the neutral biomolecule 9-EtG was found to be dispersed in the exterior bulk water and the size of the liposomes remained the same as that of empty or control liposomes. When cisplatin-containing liposomes mix with 5′-GMP-embedded liposomes or liposomes with 9-EtG, the N7 nitrogen atom of 5′-GMP or 9-EtG binds the cisplatin, thus replacing the “leaving groups” and forming a bisadduct. After 48 h of mixing, the size of the liposomes changes for the mixture of 5′-GMP-embedded liposomes and cisplatin-containing liposomes. We used 1H and 31P NMR spectroscopic techniques to monitor incorporation or association of cisplatin and biomolecules with liposomes and their subsequent reactions with each other. The dynamic light scattering technique provided the size distribution of the liposomes in the presence and absence of probe molecules.

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Acknowledgments

This work was supported by funding from the start-up fund of Kennesaw State University (KSU), Chemistry and Biochemistry, the KSU Incentive fund (CETL), and the KSU CSM Mentor Protégé fund (BARUAH-05-FY2011-01) awarded to B.B. B.B. would like to thank Dr. Mark Mitchell, Department Chair, Dr. Laurence Peterson, former Dean, and Dr. Ronald Matson, current Dean of the College of Science and Mathematics for their enormous support. B.B. is thankful to Dr. Jason Locklin at the University of Georgia and Dr. David Gottfried at the Georgia Institute of Technology Nanotechnology Research Center for help with the DLS experiments. B.B. thanks Dr. Michael Miller at Auburn University for the TEM measurements, and would also like to thank Dr. Kevin Gwaltney for his assistance with the NMR measurements and Mr. Benjamin Huck for his constant support in setting up the laboratory. B.B. is also thankful to Dr. Sandra Bonetti from Colorado State University–Pueblo for careful proofreading of the manuscript.

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  1. Department of Chemistry and Biochemistry, Kennesaw State University, Kennesaw, GA, 30144-5591, USA

    Bharat Baruah & Alexandr Surin

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  1. Bharat Baruah
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Correspondence to Bharat Baruah.

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Baruah, B., Surin, A. Interaction of liposome-encapsulated cisplatin with biomolecules. J Biol Inorg Chem 17, 899–910 (2012). https://doi.org/10.1007/s00775-012-0907-y

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