Light-Activated Cancer Drugs at UK

Light-Activated Cancer Drugs at UK


VO: At the University of Kentucky, Assistant
Professor of Chemistry Phoebe Glazer is looking for something more effective at killing cancer
cells and less toxic to healthy cells than cisplatin. A platinum-based drug, cisplatin
is one of the most commonly used cancer drugs, but leads to nausea and nerve damage. Phoebe Glazer: Cisplatin essentially does
a lot of damage in rapidly proliferating cells. So that’s why it’s good as a cancer drug,
and it will work on a variety of different types of cancers. The problem is–it will
kill all types of cells. There’s this really narrow window between a therapeutic dose where
you’re effectively killing the cancer, and the toxic dose where you’re essentially killing
the patient. That’s why I was motivated to start this project. VO: Glazer’s lab team has an alternative,
a drug based on ruthenium. Phoebe Glazer: Ruthenium is another transition
metal. It’s in the middle of the Periodic Table, and its right underneath iron. Unfortunately,
like platinum, it’s a precious metal, so it’s not cheap. The reason people really like ruthenium
is because you can make complexes out of it that are useful in a wide variety of applications. You can keep the metal center, the ruthenium,
the same, and put different organic ligands around it. So if you want to make a sophisticated
looking molecule–a complex molecule–you can swap out the different organic pieces
and build in three dimensions molecules that will look different and potentially have different
functions and behavior. That’s why we think it’s a good scaffold that you can use to build
a drug. VO: Postdoc Matthew Dickerson explains how
these ruthenium-based drugs would kill tumors. MATTHEW DICKERSON: What I’m trying to do is
I’m trying to take the molecules, put them into nanoparticles to prolong the circulation
time in the body, as well as hopefully deliver them to the tumor more effectively. One of the major limiting factors in traditional
chemotherapy is the fact that it’s non-targeted. You basically inject it into the patient,
and it goes where it will. What we want to do is target the chemotherapeutics
directly to the tumor. We can inject those into the patient, and then when we hit the
patient with light–locally to the tumor–only the compounds actually in the tumor activated
so that they become toxic. VO: Using light from a fiber-optic probe,
Glazer’s ruthenium molecules would be switched on, and cause DNA damage only to the cancerous
tumor. DAVID HEIDARY: We’re also trying to uncover
how these molecules work. How do they attack the cell in such a way that it causes them
to die in the presence of light? So we’re investigating the mechanism of action for
these molecules. YANG SUN: This is the most exciting part of
the project because we’ve found that some of the compounds kill cells by targeting DNA
and damaging DNA. Phoebe Glazer: If you can create a molecule
that in its intact form is inactive, but when you shine light on it, you create a DNA damaging
component and then another component that would have a totally different activity. Then
you have the chance of hitting the cell twice. That’s the hypothesis–that’s the idea. One
drug could have two different mechanisms. VO: Glazer has shown that these ruthenium
molecules are up to three times as potent as cisplatin. In January 2013, she received
a four-year grant from the American Cancer Society to develop a family of ruthenium molecules
to fight different kinds of cancer. Phoebe Glazer: Taking it from essentially
some initial molecules that prove that the concept works to the point where we might
actually have molecules that have a chance of helping someone. 2

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