Cristina Zavaleta, an assistant professor in the Department of Biomedical Engineering at USC Viterbi in Los Angeles, has just developed new imaging contrast agents with his team using common dyes such as tattoo ink and food coloring. When these dyes are attached to nanoparticles, they can illuminate tumors, allowing medical professionals to better differentiate between tumor cells and normally adjacent cells and detect cancer. The work was published in Biomaterials Science.
The importance of diagnostics
La diagnosis early is critical for patients to have the best possible outcomes from cancer; a disease that will affect over 38% of Americans at some point in their life.
However, detection is challenging without good imaging agents; contrast materials that, when injected into patients, allow images such as MRI and CT to function with improved sensitivity and specificity, enabling medical professionals to accurately detect and diagnose cancer, and surgeons to identify exact margins of tumors.
“For example, if the problem is colon cancer, this is detected via endoscopy,” he said Zavaleta. “But an endoscope is literally just a flashlight on the end of a stick, so it will only provide information about the structure of the colon – you can see a polyp and know you need to do a biopsy. If we could provide imaging tools to help doctors see whether that particular polyp is cancerous or just benign, often there wouldn't even be a need to intervene,” she said.
How the system works
Illuminated nanoparticles move through a blood vessel to detect cancer. The dyes were incorporated into the nanoparticles to enable more precise imaging contrast when identifying cancer cells. To achieve this, the team discovered a unique source of optical contrast agents from the household dyes and coloring pigments we routinely encounter. These “optical inks” can be applied to targeted nanoparticles to improve cancer detection and localization.
The dyes and pigments were derived from common coloring agents.
The idea? It came from Pixar
For Zavaleta, inspiration came from an unusual place: an animation class with Pixar artists in Emeryville, California, the home of the famed animation studio. Zavaleta, who loves art and animation, said she was intrigued by the inks and paints the artists brought to the classroom. “I was thinking about how these very high-pigment paints, like gouache watercolors, were brilliant in a way I had never seen before, and I was wondering if they had interesting optical properties,” Zavaleta said.
The idea took her to a tattoo artist in nearby San Francisco, Adam Sky, another craftsman who works with bright dyes.
I remember bringing a 96-well plate and he sprayed tattoo ink into each of the wells. Then I took the inks to our Raman scanner (used to sensitively detect tumor-targeted nanoparticles) and discovered these truly amazing spectral fingerprints that we could use to encode our nanoparticles. It was great.
Cristina Zavaleta, USC Viterbi – Los Angeles
The challenges to be faced in detecting cancer
One of the safety challenges of nanoparticle imaging is that they can often have prolonged retention in organs such as the liver and spleen. Because of these safety concerns, it is critical to consider biodegradable nanomaterials. There are currently a limited amount of optical contrast agents approved for clinical use.
With this in mind, Zavaleta's team considered common food dyes that could be used for nanoparticles, such as dyes found in colorful candies like Skittles and M&M's. These brightly colored food products that humans routinely consume have been deemed safe for human consumption by the FDA.
“We thought: Let's look at some of the FDA-approved pharmaceutical, cosmetic and food colorants that exist and see what optical properties are among those colorants,” Zavaleta said. “And that's where we found that many of these FDA-approved dyes have interesting optical properties that we could exploit for imaging.”
The team has developed a nanoparticle that will carry these highly pigmented imaging agents as a “payload” to detect cancer. Zavaleta said the particles have a specific size. This allows some of them to passively penetrate tumor areas. Others, appropriately chosen, to be held back due to their size.
The nanoparticle can also be “decorated” with a larger payload of dye than previous imaging agents. This will lead to a brighter and more effective signal in detecting cancer. “If you encapsulate a bunch of dyes in a nanoparticle, you'll be able to see it better because it will be brighter,” Zavaleta said.
