- Inside UNM
For several decades, doctors and scientists have worked to develop methods for treating cancer that improve patient outcomes and avoid unpleasant side effects associated with traditional chemotherapy. Researchers at UNM and Sandia Labs have made a significant step toward achieving this goal by developing a novel type of nanoparticle, called a "protocell," capable of delivering drugs and other types of therapeutic molecules specifically to cancer cells.
The core of the protocell is a porous silica nanoparticle that acts as a nano-sized sponge, soaking up high concentrations of drugs. The drug-laden core is wrapped in a lipid bilayer, which is similar in composition to a cell membrane and prevents drugs from prematurely leaking out of the core. Molecules that recognize cancer cells are then attached to the lipid bilayer so that protocells are taken up by cancer cells while bypassing normal cells. The type and density of these molecules, called targeting ligands, can be tailored to target different types of cancers.
The protocell's ability to kill cancer cells without harming normal cells was originally reported in an article featured on the cover of the scientific journal "Nature Materials" in May 2011. This article demonstrated that protocells loaded with a cocktail of chemotherapy drugs and targeted to liver cancers are one million times more effective at treating cancer than other types of targeted delivery vehicles.
A second paper appeared on the cover of the March 2012 edition of "ACS Nano" and described the ability of protocells loaded with a new type of cancer therapeutic called small interfering RNA or siRNA, to kill an entire population of liver cancer cells at vanishingly small concentrations of siRNA.
What is unusual in this research success story is the role undergraduate students are playing. One UNM chemical engineering junior, Katharine Epler, is the lead author on a new paper "Delivery of Ricin Toxin A-Chair by Peptide-Targeted Mesoporous Silica Nanoparticle-Support Lipid Bilayers" which will be featured on the cover of "Advanced Healthcare Materials" next month.
Epler summarized the major findings of the paper by saying "ricin toxin is a protein isolated from Castor beans and nefarious for its use in the assassination of Georgi Markov. Ricin is composed of two subunits or chains – A and B. The B-chain promotes uptake by cells, while the A-chain kills cells by inhibiting protein synthesis. By loading protocells with ricin toxin A-chain, we can selectively kill liver cancer cells while sparing normal liver cells. Working with ricin toxin A-chain (as opposed to the intact toxin) is also much safer for us, since A-chain is only toxic if it has a way to get inside of cells. This is why protocells are well-suited for delivery of especially toxic molecules – protocells loaded with ricin toxin A-chain and targeted to cancer are almost exclusively taken up by cancer cells and are not toxic to other types of cells."
Epler became involved in development of the protocell during the summer of 2009, just after she graduated from high school. That is when she met and began working with Assistant Research Professor in the Department of Chemical and Nuclear Engineering Eric Carnes, who is a member of the research group led by Distinguished Professor of Chemical and Nuclear Engineering, UNM Cancer Center member and fellow at Sandia National Laboratories C. Jeffrey Brinker. Although Epler had no prior lab experience she learned quickly under Carnes' tutelage.
"I remember being a bit overwhelmed during my first few months," she said. "Dr. Carnes has been very supportive." Carnes explains, "Dr. Brinker and I have high expectations for our students. Undergraduate students are expected to perform at the graduate student level, while graduate students are expected to perform at a post- doctoral or faculty level. However, Katie has exceeded our expectations. By the time she graduates, she will be the lead author of at least three papers. This level of achievement is quite rare."
About a dozen undergraduates work in Brinker's new Nanoscience and Nanomedicine Lab at the Centennial Engineering Building. Most will be lead author of at least one paper before graduating with a B.Sc. degree and all agree that their research achievements are made possible by the support and mentorship provided by senior members of the group such as postdoc Jason Townson. Epler follows the footsteps of another successful graduate Carlee Ashley, who now works for (SNL).
Epler's research accomplishments are an important step toward meeting the goals of a Cancer Nanotechnology Platform Partnership (CNPP) grant funded through the National Cancer Institute and lead by Brinker and Director and CEO of the UNM Cancer Center Cheryl Willman.
This interdisciplinary research effort involves a team of cancer biologists, materials scientists and chemical engineers and focuses on developing ways to treat poor prognosis childhood leukemia. Biologists involved in the project are identifying molecules over-expressed by drug-resistant forms of acute lymphoblastic leukemia (ALL), while the engineers are developing drug-filled nanoparticles that target those molecules and might be able to selectively the disease while minimizing collateral damage to non-diseased cells.
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