Putting the Sting on Cancer

Summer 2014


Insects have always fascinated Gregory Wiedman. Luckily, the materials science graduate student has been able to connect his bug-collecting hobby with his research. In the materials science lab of Kalina Hristova, the Marlin U. Zimmerman Jr. Faculty Scholar, Wiedman is developing a new drug delivery system based on a toxin found in honeybee venom.

The toxin, melittin, is a peptide—a short string of amino acids—that kills cells by drilling holes in their protective outer membranes. Scientists have been trying to harness this property to destroy tumor cells. But melittin attacks indiscriminately, killing healthy cells along with cancerous ones.

Wiedman, through a training grant funded by the Institute for NanoBioTechnology, is trying to engineer the peptide to pierce cell membranes in response to a specific pH level. Because tumors are known to have lower pH than blood, the idea is that pH-triggered melittin would only destroy cancer cells.

The engineered peptide could also be used to effectively deliver cancer drugs inside tumors. When drug molecules come in contact with a cell, the cell defends itself by enveloping them in its membrane to form structures called endosomes, which break down the molecules over time. But the pH-activated melittin could get around this defense mechanism. That’s because, Wiedman explains, the pH level inside endosomes dips over time. He envisions a drug-delivery system in which the melittin is attached to a drug molecule.

“If you can get both into the endosome, the peptide could open up the endosome inside the cell when the pH drops,” he says.

Melittin is a string of 26 amino acids. By altering each acid in the sequence, Wiedman has created a library of more than 18,000 peptide mutations. He is now testing these mutations in the lab to see which one has the desired pH sensitivity. The challenge, he says, is to change just the right number of amino acids so that the melittin becomes pH-sensitive but doesn’t lose its crucial cell-puncturing property.

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