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Posted: Aug 29, 2008
Targeting nanoparticles to specific locations inside cancer cells increases kills
(Nanowerk News) The ability to target nanoparticles to specific types of cancer cells is one of the main reasons that nanoparticles have gained favor as a promising drug delivery vehicle. By increasing the amount of an anticancer agent that gets to tumor cells, as opposed to healthy cells, researchers hope to minimize the potential side effects of therapy while maximizing therapeutic response. Now, a team of investigators at Northeastern University has taken this approach one step farther by targeting the specific location inside a tumor cell, where the drug ceramide exerts its cell-killing activity.
Reporting its work in the journal Nano Letters ("Organelle-targeted nanocarriers: specific delivery of liposomal ceramide to mitochondria enhances its cytotoxicity in vitro and in vivo")), a team of investigators led by Volkmar Weissig, Ph.D., who has since moved to the Midwestern University College of Pharmacy in Glendale, AZ, developed a lipid-based nanoparticle and decorated its surface with a molecule known as triphenylphosphonium cation, which is known to be taken up specifically by mitochondria, the cell's energy-producing organelles. The investigators then loaded this nanoparticle with ceramide, a drug that forms holes in the mitochondrial membrane, which in turn triggers cell death by a process known as apoptosis. Ceramide also has been shown to work in concert with other anticancer agents to overcome the multiple drug resistance that develops in many tumors.
Using this formulation, Dr. Weissig and his colleagues observed that targeted cells—and only targeted cells—treated in culture accumulated ceramide in their mitochondria. Moreover, the researchers found that only the targeted nanoparticle was able to deliver ceramide to the mitochondria and trigger apoptosis. Untargeted nanoparticles loaded with ceramide, as well as free ceramide, did not accumulate in mitochondria, nor did they trigger apoptosis.
When administered to tumor-bearing mice, the investigators found that ceramide-loaded, targeted nanoparticles had a significant impact on reducing the tumor growth rate. In contrast, untargeted ceramide-loaded nanoparticles, targeted but empty nanoparticles, and free ceramide had no effect at the dose tested. The researchers note that previous studies with ceramide have shown that 6 times more drug than that administered in the nanoparticles was needed to see any therapeutic effect.