’Molecular jackhammers’ show potential to kill cancer cells within minutes
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Researchers have harnessed the ability of some molecules to vibrate strongly when stimulated by light, potentially laying the groundwork for a new approach to destroying cancer cells.
When stimulated by near-infrared light, the atoms of a small dye molecule used for medical imaging can vibrate in unison. This forms what is known as a plasmon and triggers the rupture of the cell membranes of cancer cells.
The method — known as vibronic-driven action — resulted in complete elimination of human melanoma cells in in vitro experiments, findings published in Nature Chemistry showed. Treatment eliminated half of melanoma tumors in mice.
“Our next step will be to start a new study on pancreatic cancer in vivo with mouse models, and we are trying to optimize parameters,” investigator Ciceron Ayala-Orozco, PhD, research scientist at the Tour lab at Rice University, told Healio. “This was very effective in vitro, and there is a chance that this could also become effective in vivo. Of course, as we move from mouse to human, it becomes more challenging.”
From motors to molecules
The Tour lab previously used nanoscale compounds equipped with a light-activated, paddle-like chain of atoms to drill through the outer membranes of infectious bacteria, cancer cells and treatment-resistant fungi.
The new approach relies on what some refer to as “molecular jackhammers”, which — unlike nanoscale drills — can be activated with near-infrared light rather than visible light. They also are much faster in their mechanical motion.
“The near-infrared light is what allowed us to even think about moving this to clinical translation,” Ayala-Orozco said. “UV light and blue light don’t go deep into the tissue — only a few millimeters. Near-infrared light can go centimeters into the tissue without causing damage.”
After many years of trying with minimal success to work with blue-light activated motors to treat tumors in mice, Ayala-Orozco decided to explore different mechanisms of action.
“I started to think that maybe what I needed was not necessarily a motor, but a molecule that absorbs near-infrared light, in the hopes that this molecule could be activated and could move in a different way — not necessarily by rotation,” he said. “That’s when I started thinking about some molecules called cyanines and started connecting the dots with a property from photophysics called plasmons, which I studied during my PhD to treat cancer. They are activated by near-infrared light. At some point, I decided I had to try this.”
A moving, ‘breathing’ molecular machine
Ayala-Orozco and colleagues developed the molecular jackhammers using aminocyanine molecules, a class of fluorescent synthetic dyes used in imaging.
“This is a molecule that works through vibration, but not just any type of vibration — it’s a collective vibration,” he said. ‘That means all the atoms within the molecule are moving in unison. It’s as if the molecule was breathing, because it’s moving longitudinally and also transversally. It’s also very fast — it moves at a rate of 40 trillion oscillations per second.”
This fast-moving mechanical force is such that “anything around it will be disassembled,” Ayala-Orozco said. In this case, the cellular membranes and cellular structures that are disassembled.
“That is what causes the cell to die within minutes,” he said. “We saw immediately in the first trial that all the cells were just dead after treatment in this way.”
More recent studies showed the molecular jackhammers were equally effective during in vitro analyses of colorectal cancer, prostate cancer and breast cancer cells.
“No matter which line, we are able to eliminate 100% on cell culture,” he said.
Additional studies are planned to further evaluate this strategy in mice. The university will need to partner with a company to develop the approach and achieve regulatory milestones.
“There is a company already working on this, and they are interested in licensing it,” Ayala-Orozco said. “I think the cyanine molecules will facilitate FDA approval, because it belongs to a class of molecules from which some are already FDA approved and used in the clinic for other purposes. It’s not exactly the same molecule as in the clinic but, because it has similar features, it will facilitate the clinical translation. Then hopefully, within 5 to 7 years, the company could be starting the first clinical trials in humans.”
For more information:
Ciceron Ayala-Orozco, PhD, can be reached at Rice University, P.O. Box 1892, Houston TX 77251-1892; email: ca5@rice.edu.
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