This month, Molecular Pharmaceutics reported promising findings from the Nemours Center for Childhood Cancer Research and the Materials Science and Engineering Department at the University of Delaware, about the potential for nanotechnology to deliver chemotherapeutic agents in a way that attacks cancer cells without harming healthy cells.
To date, nanoparticle-based drug delivery approaches have been poorly developed for the treatment of childhood leukemia, which comprises 30 percent of childhood cancers. In the Nemours study, encapsulated dexamethasone ("dex") delivered to pre-clinical models with leukemia significantly improved the quality of life and survival compared to the control receiving the unencapsulated drug.
Acute lymphoblastic leukemia (ALL) is the most common form of pediatric leukemia. Although five-year survival rates for ALL approach 90 percent with available chemotherapy treatments, the harmful side effects of the drugs, including secondary cancers and fertility, cognitive, hearing, and developmental problems, present significant concern for survivors and their families.
Studies conducted by the lead author A. K. Rajasekaran, PhD, and his team at Nemours in collaboration with Xinqiao Jia, PhD, and her team at the University of Delaware, used polymeric nanoparticles containing chemotherapeutic agents to ensure controlled delivery of drugs to cancer cells in preclinical models.
"There are currently seven or eight drugs that are used for chemotherapy to treat leukemia in children," said Dr. Rajasekaran. "They are all toxic and do their job by killing rapidly dividing cells." However, he explained, these drugs don't differentiate cancer cells from other healthy cells. "The good news is that these drugs are 80 to 90 percent effective in curing leukemia. The bad news is that many chemotherapeutic treatments cause severe side effects, especially in children." He posits that it will take researchers hundreds of millions of dollars and many years to find better alternative drug treatments. In the interim, scientists like Dr. Rajasekaran and his colleagues are working on novel ways to deliver existing and affordable drugs to children.
"Our polymer synthesis and particle engineering are guided by the clinical need for reducing the side effects of cancer drugs," Dr. Jia commented.
Vinu Krishnan, the first author of the study and a chemical engineer and graduate student in Materials Science and Engineering, said, "I am very excited about the results and look forward to taking this to the next level and introducing this approach for the clinical treatment of childhood leukemia."
Students in Dr. Jia's group contributing to this work include Xian Xu and Xiaowei Yang.
To date, advances in nanotechnology have been primarily concentrated around adult cancers. Nanotechnology involves the use of encapsulated particles of drugs that go into the core of the cell. The nanoparticles stick only to the cancer cells and destroy them by delivering the drug precisely, without detecting or harming the normal cells.
In preclinical models of leukemia, Dr. Rajasekaran and his team were able to improve survival and quality of life via nanotechnology. Encapsulating the drug uses one third of the typical dose, with good treatment results and no discernible side effects. In addition, the mice that received the drugs delivered via nanoparticles survived longer than those that received the drug administered in the traditional way.
This work is supported by National Institutes of Health (RO1 DK56216, P20RR016458, P20 RR017716), Delaware Health Sciences Alliance, Andrew McDonough B + Foundation, Caitlin Robb Foundation, Kids Runway for Research, Sones Brothers, Nemours Foundation and funds from the University of Delaware.
- Vinu Krishnan, Xian Xu, Sonali P. Barwe, Xiaowei Yang, Kirk Czymmek, Scott A. Waldman, Robert W. Mason, Xinqiao Jia, Ayyappan K. Rajasekaran. Dexamethasone-Loaded Block Copolymer Nanoparticles Induce Leukemia Cell Death and Enhance Therapeutic Efficacy: A Novel Application in Pediatric Nanomedicine. Molecular Pharmaceutics, 2012; 121129010029000 DOI: 10.1021/mp300350e
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