Low Doses of Cisplatin Delivered by Targeted Nanoparticles Reduce Growth of Prostate Cancer

Nanoparticles loaded with a pro-drug form of the platinum-based drug cisplatin have been used to effectively treat rodent models of human prostate cancer at doses of the drug that minimize its severe side effects.

Despite these 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.

To minimize the toxic effect of cisplatin treatment for prostate cancer investigators at Harvard University (Cambridge, MA, USA) developed a novel delivery system based on nanoparticles labeled with an aptamer that targets the extracellular domain of the prostate specific membrane antigen (PSMA). The nanoparticles are loaded with a pro-drug form of cisplatin that becomes activated only after delivery to the target cells.

Results published in the January 13, 2010, online edition of the journal Proceedings of the [US] National Academy of Sciences (PNAS) revealed that the nanoparticles circulated in the bloodstream for about 24 hours, at least five times longer than unencapsulated cisplatin. The prolonged persistence of cisplatin in the systemic blood circulation was accompanied by decreased accumulation of platinum in the kidneys, a major target site of cisplatin toxicity. 


When tested in rat and mouse models of human prostate cancer, the nanoparticle-delivered drug reduced tumor size to the same extent as conventional cisplatin over a 30-day period, but with only 30% of the dosage.

"Additional animal testing is needed before the cisplatin-carrying particles can go into human clinical trials,” said senior author Dr. Omid Farokhzad, associate professor of nanomedicine and biomaterials at Harvard University. "At the end of the day, if the development results are all promising, then we would hope to put something like this in humans within the next three years.”

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