The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs
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- 作者：Timothy C. Johnstone ; Kogularamanan Suntharalingam ; Stephen J. Lippard
- 刊名：Chemical Reviews
- 出版年：2016
- 出版时间：March 9, 2016
- 年：2016
- 卷：116
- 期：5
- 页码：3436-3486
- 全文大小：2330K
- 年卷期：Timothy C. Johnstone completed his B.Sc. (Hons) at McGill University in 2009. At the Massachusetts Institute of Technology, he subsequently carried out his doctoral research under the supervision of Prof. Stephen Lippard on the chemistry and nanodelivery of platinum anticancer agents. In 2014, he joined the laboratory of Prof. Elizabeth Nolan at MIT and investigated siderophore–antibiotic conjugates for antibacterial applications. He is currently an NSERC postdoctoral fellow at the University of Toronto, carrying out Frustrated Lewis Pair research in the group of Prof. Doug Stephan.Kogularamanan “Rama” Suntharalingam obtained a M.Sci. degree in Chemistry from Imperial College London (UK) in 2008. Rama was awarded his Ph.D. in Chemistry from the same institute in 2012. His Ph.D. research was carried out under the mentorship of Prof. Ramon Vilar. Rama joined Prof. Stephen J. Lippard’s research group at Massachusetts Institute of Technology (MA) as a Misrock Fellow in 2012. He was then awarded the Dalton Young Researchers Award by the Royal Society of Chemistry in 2014. In the same year, he began his independent research group at King’s College London. His current research combines facets of inorganic chemistry, nanotechnology, and molecular biology.Stephen J. Lippard is the Arthur Amos Noyes Professor of Chemistry at MIT, where he was head of the department from 1995 to 2005. His work on platinum complexes began with initial studies that provided electron-dense reagents for use in electron microscopy and macromolecular crystallography, continued with work that elucidated the nature of “platinum blues”, and for many years has contributed to our understanding and designed improvement of platinum anticancer drugs and drug candidates. He recently cofounded Blend Therapeutics to help advance novel platinum compounds for cancer therapy.
- ISSN：1520-6890
文摘
The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-threat agents, and photoactivatable platinum(IV) complexes. Nanoparticles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations, including supramolecular self-assembled structures, proteins, peptides, metal–organic frameworks, and coordination polymers, will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also will reflect our optimism that the next generation of approved platinum cancer drugs is about to arrive.