The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs
By T. Johnstone, K. Suntharalingam, S. Lippard. Chemical Reviews, 2016
2,029 citations recorded by the source corpus.
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 non-classical 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 non-classical platinum(II) complexes with trans geometry and with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-treat agents, and photoactivatable platinum(IV) complexes. Nanodelivery particles 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 reflect our optimism that the next generation of platinum cancer drugs is about to arrive.
Subfields: Biomaterials, Oncology, Organic Chemistry
View Paper: https://www.semanticscholar.org/paper/2453b61a731df1dd8c4f00d3f1420ea93987a939
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Citations in the corpus
- Platinum-based drugs for cancer therapy and anti-tumor strategies (2022, methodology): “This replacement is triggered by the significantly lower intracellular chloride ion concentration (about 4 mM) compared to the extracellular matrix (about 100 mM), promoting transformation to cationic hydrate, such as cis-[Pt(NH3)2Cl(OH2)]+ and cis-[Pt(NH3)2(OH2)2]2+ [44].”
- Metal complexes in cancer therapy – an update from drug design perspective (2017, neutral): “30 For instance, estrogen receptor (ER) is a known drug target because of high expression of this protein on the surfaces of some cancer cells, particularly in breast cancer.”