Tracing cancer with tattoo ink

USC researchers say tattoo inks and food dyes could help improve cancer detection

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Tracing cancer with tattoo ink

LOS ANGELES—Tattoo ink could prove an unlikely new method for improving cancer detection, thanks to new research from the University of Southern California (USC).

Dr. Cristina Zavaleta, WiSE Gabilan Assistant Professor in the Viterbi Department of Biomedical Engineering, also has a lab at USC’s Michelson Center for Convergent Bioscience. She and her team have recently developed new imaging contrast agents from common dyes like tattoo ink and food coloring, and their research has been published in Biomaterials Science.

Early detection is crucial for cancer patients to have the best outcomes, but detection is challenging without good imaging agents. Contrast materials allow for imaging like MRI and CT to function with better sensitivity and specificity, enabling medical professionals to diagnose with accuracy—and for surgeons to identify the exact margins of tumors.

“For instance, if the problem is colon cancer, this is detected via endoscopy,” Zavaleta said. “But an endoscope is literally just a flashlight on the end of a stick, so it will only give information about the structure of the colon. You can see a polyp and know you need to take a biopsy, but if we could provide imaging tools to help doctors see whether that particular polyp is cancerous or just benign, maybe they don’t even need to take it.”

The team discovered a unique source of optical contrasting agents from common coloring dyes that already have FDA approval. These dyes can be attached to cancer-targeting nanoparticles to improve cancer detection and localization. The team hopes that the dyes’ approved status could more easily enable their implementation into imaging practices.

Zavaleta took inspiration from paints at an art class, she explained: “I was thinking about how these really high pigment paints, like gouache watercolors, were bright in a way I hadn’t seen before, and I was wondering if they had interesting optical properties.”

That idea led her to a tattoo artist.

“I remember I brought a 96-well plate and he squirted tattoo ink into each of the wells. Then I took the inks to our Raman scanner and discovered these really amazing spectral fingerprints that we could use to barcode our nanoparticles,” Zavaleta added. “It was super cool.”

One of the challenges of using nanoparticles in imaging is their prolonged retention in organs like the liver and spleen. Safety concerns warrant the consideration of biodegradable nanomaterials, and there are a limited amount of optical contrast agents approved for clinical use.

“We thought, ‘let’s look at some of the FDA-approved drug, cosmetic and food dyes that exist and see what optical properties are amongst those dyes,’” continued Zavaleta. “[W]e ended up finding that many of these FDA-approved dyes have interesting optical properties that we could exploit for imaging.”

“For tattoo inks, we have shown optical imaging potential using all the colors of the rainbow, as shown in our paper. There are some colors, however, that demonstrate multiple optical properties, like the ability to fluoresce brightly. Orange in particular has this unique ability to be used as a multimodal imaging contrast agent,” she tells DDN. “This can give physicians more information about where these contrast agents are localizing in the body (i.e., directed to cancer).

“All of the FDA-approved food, drug and cosmetic dyes have shown promise to provide optical imaging contrast via Raman spectroscopy. Some of the drug and cosmetic dyes in particular have shown bright fluorescence imaging capabilities as well—including the green, yellow and red dyes.”

Most of the imaging contrast agents used in the clinic today are small-molecule dyes.

“With small molecules, you may be able to see them accumulate in tumor areas initially, but you’d have to be quick before they end up leaving the tumor area to be excreted,” noted Zavaleta. “Our nanoparticles happen to be small enough to seep through, but at the same time big enough to be retained in the tumor, and that’s what we call the enhanced permeability and retention effect.”

The nanoparticle can also be filled with a larger payload of the dye than previous small-molecule dyes. The team has shown under fluorescence imaging that this leads to brighter signal and significant localization of the nanoparticles in tumors.

“Using dyes that exhibit multiple optical imaging properties could improve the accuracy and precision of how we detect cancer. Using multiple modes of imaging could allow physicians to interrogate more information about the tumor itself and where it is hiding,” Zavaleta points out. “Each mode of imaging can tell you different things about the tumor and its location. Combining the advantages of using multiple imaging techniques makes for a powerful tool to aid physicians in localizing and treating the tumor.”

She also states that the new dyes are useful in other fields besides oncology, explaining that “There are several clinical applications that could benefit from their sensitive and specific imaging contrast properties (i.e., detecting and localizing areas of inflammation). Moving forward, we would want to ensure that our dye-encapsulated nanoparticles are stable for several hours. Nanoparticles delivered to tumor sites via intravenous injection have shown prolonged accumulation in the tumor area itself for longer than 24 hours.”

“Our lab will continue to develop new nanoparticle formulations and delivery strategies to ensure that our imaging contrast agents are able to provide physicians with improved cancer detection capabilities. We want to exploit the multimodal features of these coloring dyes to provide the combined imaging qualities of high sensitivity, high specificity, real-time image guidance and deeper imaging capabilities,” she concludes. “We are particularly excited about the opportunity to provide unprecedented multiplexed imaging information to the physician. This could enable a more personalized treatment regimen for the patient and improve their overall therapeutic outcome.”

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