Can Silver Replace Platinum for Chemotherapy?

Bidentate silver compounds (where a ligand is bound to the central silver atom through two sites) were found to be more effective anticancer agents than were those where the ligand was coordinated through only one site (monodentate).

Recorded use of silver to prevent infection dates to ancient Greece and Rome; it was rediscovered in the Middle Ages when it was used for several purposes, such as to disinfect water and food during storage, and also for the treatment of burns and wounds as wound dressing. Silver solutions were approved in the 1920s by the [US] Food and Drug Administration for use as antibacterial agents.

The most common metal used in chemotherapeutic agents is platinum. Despite severe adverse side effects, which include kidney and nerve damage and nausea, cisplatin remains the drug of choice for treatment of many types of cancer, with about half of all cancer patients receiving platinum-based chemotherapy. Another drawback of conventional cisplatin treatment is the drug’s relatively short lifetime in the bloodstream. Only about 1% percent of the dose given to a patient reaches the target cells, and about half the dose is excreted within an hour of treatment.

In a preliminary study to test the suitability of silver compounds for use in chemotherapy, investigators at the University of Leeds (United Kingdom) cultured breast and colon cancer cells with different silver-based chemicals for six-day periods. They reported in the January 6, 2012, online edition of the journal Dalton Transactions that several cationic silver complexes bearing bis(N-heterocyclic carbene) ligands exhibited cytotoxicity comparable to cisplatin. Bidentate ligands showed enhanced cytotoxicity over monodentate and macrocyclic ligands.

The enhanced cytotoxicity of the bidentate compounds may have been be due to protracted release of the silver atoms, which made these compounds more effective over a longer period of time.

First author Dr. Charlotte Willans, a chemistry research fellow at the University of Leeds, said, “As many are unfortunately aware, chemotherapy can be a very grueling experience for the patient. Finding effective, yet nontoxic drugs is an ongoing problem, but these preliminary results are an important step in solving it. Our research has looked at the structure, which surrounds a central silver atom. This “shrubbery” is what determines how reactive it is and what it will interact with. Our research has used different types of these ligands to see which is the most effective against cancer cells.”

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University of Leeds