Nanoparticles Send Doxorubicin to Cancer Target
In mice, this targeted delivery results in 15-fold increase in drug efficacy with few side effects
THURSDAY, July 10 (HealthDay News) -- Using nanoparticles to deliver targeted doxorubicin to tumor vasculature in mice resulted in greatly improved drug efficacy with minimal side effects, according to research published online July 8 in the Proceedings of the National Academy of Sciences.
Eric A. Murphy, Ph.D., of the University of California San Diego in La Jolla, Calif., and colleagues describe their work using nanoparticles encapsulating doxorubicin that targeted integrin ανβ3, which is found in angiogenic endothelium in malignant tissue.
In mice implanted with pancreatic tumors, targeted nanoparticles with 1 mg/kg of the drug resulted in a 23 percent reduction in the primary tumor growth and an 82 percent reduction of metastasis to the hepatic hilar lymph node compared to control animals, the researchers report. Neither an untargeted nanoparticle with the drug or the same amount of free doxorubicin had a significant effect. To achieve the same anti-cancer effects of the targeted nanoparticles required 15 mg/kg of free doxorubicin, which caused severe weight loss in the animals.
"Doxorubicin is dose-limited by cardiotoxicity, and lower doses greatly reduce the side effects of this chemotherapeutic agent," the authors write. "It will be interesting to use this approach with a number of the newer pharmacological agents designed to suppress tumor or vascular cell signal transduction. Although some of these agents are beginning to show promise in the clinic, targeted nanoparticle delivery would likely reduce the concentration needed for efficacy and minimize problems associated with pharmacokinetics and/or side effects."