A new drug delivery technique may hold promise for more efficient cancer therapies. The technique involves storing a cancer drug inside tiny objects called nanoparticles. Using this method, researchers were able to shrink tumors in mice while using smaller doses of the drug to reduce harmful side effects.
The chemotherapy drug cisplatin is an effective cell killer. It's used against half of all human cancers. However, cisplatin carries serious side effects, like kidney and nerve damage. These side effects limit the dose that can be used, which is a problem because the drug only lasts in the bloodstream for a short time.
Nanoparticles are emerging as an efficient tool to deliver therapies. They can carry drug molecules and be targeted to specific cells. Recently, a team of scientists from the Massachusetts Institute of Technology and Brigham and Women's Hospital showed that they could store an inactive form of cisplatin, called a prodrug, inside nanoparticles that are engineered to target a specific protein on prostate cancer cells. Once the cells take up the nanoparticle, the prodrug is released and converted to its active form. The team showed that these drug-carrying particles kill cancer cells in culture more efficiently than the drug alone.
In the new study, some of those same researchers, led by Dr.Farokhzad and Dr. Stephen Lippard, tested whether the drug-delivering nanoparticles could serve as a safer, more effective option for chemotherapy in living animals. The work was published in the January 10, 2011, issue of the Proceedings of the National Academy of Sciences, and was funded in part by NIH’s National Cancer Institute (NCI) and National Institute for Biomedical Imaging and Bioengineering (NIBIB).
The team first tested different doses of the nanoparticle-bound drug in rats and mice. Both species survived and maintained their body weight at higher doses of the drug when it was delivered using nanoparticles than when injected on its own. They also found less kidney damage in rats that received the drug via nanoparticle.
To see whether the nanoparticles could affect how long cisplatin stays in the bloodstream, the researchers injected the prodrug into rats. One hour later, 77% of the drug remained in the blood when it was carried by nanoparticles, but less than 16% remained if it was injected alone. Moreover, less of the drug accumulated in kidneys when delivered by nanoparticles—further evidence that the method is likely to reduce kidney damage.
Finally, to see whether this mode of delivery could kill tumors more efficiently, the team injected human prostate cancer cells into mice. Once the mice developed tumors, they started treatment with either the standard dose of cisplatin or just 30% of that dose with the drug-carrying nanoparticles. After 4 weeks, the lower dose of nanoparticle-delivered drug had diminished the tumors just as much as the higher dose of free cisplatin.
Further work will be needed to show whether this technique works as well in humans as it does in small animals. If so, the targeted delivery of drugs using nanoparticles could become an exciting step into the future of cancer therapy. "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 3 years," says Farokhzad.