Tag Archives: University of Illinois at Urbana-Champaign (UIUC)

Fido’s osteosarcoma and nanoparticle drug delivery

Researchers at the University of Illinois at Urbana-Champaign have started testing nanoparticle drug delivery for bone tumours in dogs. From a July 25, 2016 news item on ScienceDaily,

At the University of Illinois, an engineer teamed up with a veterinarian to test a bone cancer drug delivery system in animals bigger than the standard animal model, the mouse. They chose dogs — mammals closer in size and biology to humans — with naturally occurring bone cancers, which also are a lot like human bone tumors.

A July 25, 2016 University of Illinois at Urbana-Champaign news release (also on EurekAlert) by Diana Yates, which originated the news item, provides more detail about the research,

In clinical trials, the dogs tolerated the highest planned doses of cancer-drug-laden nanoparticles with no signs of toxicity. As in mice, the particles homed in on tumor sites, thanks to a coating of the drug pamidronate, which preferentially binds to degraded sites in bone. The nanoparticles also showed anti-cancer activity in mice and dogs.

These findings are a proof-of-concept that nanoparticles can be used to target bone cancers in large mammals, the researchers said. The approach may one day be used to treat metastatic skeletal cancers, they said.

The dogs were companion animals with bone cancer that were submitted for the research trials by their owners, said U. of I. veterinary clinical medicine professor Dr. Timothy Fan, who led the study with materials science and engineering professor Jianjun Cheng. All of the dogs were 40 to 60 kilograms (88 to 132 pounds) in weight, he said.

“We wanted to see if we could evaluate these drug-delivery strategies, not only in a mouse model, but also at a scale that would mimic what a person would get,” Fan said. “The amount of nanoparticle that we ended up giving to these dogs was a thousand-fold greater in quantity than what we would typically give a mouse.” Fan is a faculty member of the Anticancer Discovery from Pets to People research theme at the IGB [Institute for Genomic Biology).

Using nanoparticles with payloads of drugs to target specific tissues in the body is nothing new, Cheng said. Countless studies test such approaches in mice, and dozens of “nanopharmaceuticals” are approved for use in humans. But the drug-development pipeline is long, and the leap from mouse models to humans is problematic, he said.

“Human bone tumors are much bigger than those of mice,” Cheng, an affiliate of the IGB’s Regenerative Biology & Tissue Engineering theme, said. “Nanoparticles must penetrate more deeply into larger tumors to be effective. That is why we must find animal models that are closer in scale to those of humans.”

Mice used in cancer research have other limitations. Researchers usually inject human or other tumor cells into their bodies to mimic human cancers, Fan said. They also are bred to have compromised immune systems, to prevent them from rejecting the tumors.

“That is one of the very clear drawbacks of using a mouse model,” Fan said. “it doesn’t recapitulate the normal immune system that we deal with every day in the person or in a dog.”

There also are limitations to working with dogs, he said. Dogs diagnosed with bone cancer often arrive at the clinic at a very advanced stage of the disease, whereas in humans, bone cancer is usually detected early because people complain about the pain and have it investigated.

“On the flip side of that, I would say that if you are able to demonstrate anti-cancer activity in a dog with very advanced disease, then it would be likely that you would have equivalent or better activity in people with a less advanced stage of the disease,” Fan said.

Many more years of work remain before this or a similar drug-delivery system can be tested in humans with inoperable bone cancer, the researchers said.

Here’s a link to and a citation for the paper,

Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis by Qian Yin, Li Tang, Kaimin Cai, Rong Tong, Rachel Sternberg, Xujuan Yang, Lawrence W. Dobrucki, Luke B. Borst, Debra Kamstock, Ziyuan Song, William G. Helferich, Jianjun Cheng, and Timothy M. Fan. Proceedings of the National Academy of Sciences 2016 doi: 10.1073/pnas.1603316113

This paper is behind a paywall.

Beginner’s guide to gold nanoparticles in an Academic Minute

Catherine J Murphy, professor of chemistry at the University of Illinois at Urbana-Champaign (UIUC), contributed to Inside Higher Education’s Academic Minute audio podcast series according to an April 9, 2015 news item on the organization’s website.

Murphy provides a very good beginner’s description of gold nanoparticles.

Inside Higher Education offers a transcript of the ‘minute’ by Matthew on its Academic Minute website’s Catherine Murphy webpage,

Introduction: Atomic element #79 is the precious metal more commonly known as gold.

Transcript: Nanotechnology is the study of matter on the 1-100 nanometer scale – about ten to a thousand atoms across. Many elements in the periodic table are metals, and chemists like me are figuring out ways to create tiny metal nanoparticles of different shapes and sizes – spheres, cylinders, stars, you name it. We focus on gold. The cool thing is that each shape and size of gold nanoparticle absorbs and scatters light at different wavelengths, so each size and shape has a different color. So all the colors of the rainbow, and then some, are possible with gold nanoparticles.

The reasons for these neat colors go back to understanding the fundamental nature of light. We know from Maxwell’s equations that light is an electromagnetic wave. If light impinges on a “small conducting sphere,” then there are conditions under which certain wavelengths of light lead to huge oscillations in the electron cloud around the metal, for any metal in the periodic table, as a function of the size of the sphere, the dielectric constant of the metal, and the refractive index of the medium. These equations were worked out by Gustav Mie in the early 1900’s and give us a fundamental understanding of where these brilliant colors come from. In the last 30 years, scientists have adapted his equation for all kinds of shapes beyond spheres.

But gold nanoparticles are not just pretty to look at: they can do a lot of interesting things. For instance, these gold nanoparticles also scatter light, making them easy to find in a simple optical microscope; and since gold is environmentally benign compared to other metals, people are using gold nanoparticles to image biological systems. When you shine light on gold, the absorption of light is very strong at the right wavelengths. Once the particles have absorbed all this energy, what do they do with it? They dump it out as heat to the environment, and so can raise the temperature of their surroundings by many degrees. This is the basis for what scientists call “photothermal therapy,” the idea that if you could target gold nanoparticles to cancer cells, or pathogens, then you could shine light at the wavelength you desire and kill the cancer cells or pathogens. Finally, if you make gold nanoparticles really really small, like 10 atoms across, they no longer act like a noble, unreactive metal at all; they become very active catalysts, like the catalytic converter in your car. So chemists are also very interested in figuring out the transition between unreactive and reactive nanoparticles.

For anyone who might be interested in the series, the Academic Minute covers a wide variety of topics ranging from ‘addiction vaccines’ to ‘digital transgender archives’ to ‘aeroponic gardening’ to ‘a science of the voice’ to ‘Viking social standing’ and more. The series seems to have been started in January 2011 and they’ve been adding to the list of podcasts at a lively rate (lately, it’s one per day). There are over 200 pages of audio podcasts available for your listening pleasure.