Nanotechnology concentrates drug in cancer cell mitochondria

In experiments in cell culture and in mice, adding the ability to target nanotech cancer therapy to the mitochondria within cancer cells renders the treatment more effective. One of the drugs made more effective may help to overcome the multiple drug resistance that develops in many tumors. From Nanowerk News “Targeting nanoparticles to specific locations inside cancer cells increases kills“:

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.

…When administered to tumor-bearing mice, the investigators found that ceramide-loaded, targeted nanoparticles had a significant impact on reducing the tumor growth rate.

The usefulness of targeting mitochondria in cancer cells, although promising in these experiments, may (or may not) ultimately be limited by an effect discovered by Nobel laureate Otto Warburg more than 80 years ago. He observed that most cancer cells differ from ordinary cells in that they produce energy by a process called glycolysis rather than by oxidation in mitochondria so they are less dependent than are ordinary cells on mitochondrial function.

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