Margaret Bennewitz: Diagnosing breast cancer sooner and more safely

Margaret Bennewitz, assistant professor in biomedical engineering at the WVU Statler College working on early tumor detection.

Margaret Bennewitz doesn’t like unanswered questions––certainly not those of people worried about whether or not they have breast cancer.

Research Community Spotlight Series: Written by Micaela Morrissette, WVU Research Office Communications
Photos by Paige Nesbit, Director of Marketing and Communications

Benjamin M. Statler College of Engineering and Mineral Resources

"The collaboration opportunities here are fantastic. Interactions with Health Sciences are just amazing. And if I hadn’t decided to come to WVU, I wouldn’t have started looking beyond tumors and venturing into the toxicology field."

Even before someone finds a lump in a breast, X-rays and MRIs may be used to screen for tumors. Neither technology excels when it comes to detecting tiny, first-stage tumors, although nothing matters more for saving lives than early cancer detection. 

Additionally, X-rays can miss even larger tumors in young, dense breasts with little fatty tissue, while MRI scans struggle to distinguish between benign and malignant tumors, leaving patients afraid, confused, mistrustful and potentially out of pocket for follow-up testing. 

In order for an MRI scanner to image organs, contrast agents must be injected into the body. Some of those dyes aren’t safe for people with allergies or kidney disorders, and Bennewitz has overarching concerns about heavy metal toxicity associated with gadolinium-based contrast agents.

So she’s working to replace them with something safer, better at finding small tumors early and, most critically, better at telling the difference between benign and malignant tissue.

Bennewitz’s NEMO particles – Nano-, Encapsulated Manganese Oxide particles – are microscopic particles of manganese oxide. When they encounter cancer cells, they turn on like lightbulbs, with the potential to light up a scan more brightly than current dyes, revealing smaller masses than current MRI technology can.

An assistant professor at  West Virginia University‘s  Statler College of Engineering and Mineral Resources, Bennewitz jumps at opportunities to find inspiration and collaboration in diverse disciplines. While she investigates NEMO particles’ unfolding implications for multiple forms of cancer, she is simultaneously conducting separate research into vaping’s largely unexplored effects.

“People say just because it hasn’t been done, that doesn’t mean you should do it,” Bennewitz said. “I disagree.”

Q: How do NEMO particles reveal cancerous tumors in MRI scans?

A: Current MRI dyes are “on” all the time. Wherever you inject a dye, it will light up the blood everywhere. It’s not specific or targeted, so it goes into benign and cancerous tumors and makes telling the difference between the two complex.

Our question is, can we make an agent that’s “off” when injected into vessels, so it will be transparent to the MRI in its intact form? Can we make a pH-sensitive nanoparticle that will break down in the low-pH environment of malignant cells and release manganese ions, thereby turning “on” for the MRI? 

We have to direct that particle to those low-pH environments, so we add a little peptide to the surface of the particle that makes it delicious to breast cancer cells. They want to eat the particle, so it gets pushed into their low-pH environment and broken down there, switching the signal to the “on” position that lights up the MRI scan.

The NEMO particles still enter benign tumors, but because they won’t bind to those cells like they do with cancer, our hope is that they won’t give a signal. 

Q: Cancer research can’t be easy. Have there been moments to celebrate?

A: Celia Martinez de la Torre, one of my original PhD students, started the manganese oxide nanoparticle work in my laboratory. One of my favorite moments and the best surprise was when we first synthesized manganese oxide nanocrystals. 

During the reaction, we saw it turn green, which was exciting and the first sign we were on the right track. But the real test was characterizing its crystal structure through an X-ray diffractometer. 

As that instrument takes measurements, you see the line slowly tracing across the screen and every now and then, a peak that is specific to the compound you made. It felt like they were calling the lottery numbers and everything on our ticket matched. With every peak, we got more amped up, and we high-fived when we proved we’d successfully made manganese oxide! 

Another memorable moment was with my MS student, Kasey Freshwater, who actually gave NEMO particles their name, and one of our undergraduates, Alexander Pueschel. Their work centered around testing our particles inside microfluidic tumor models. 

Earlier this year, sales specialists came to WVU to demonstrate their companies’ inverted spinning disk confocal microscopes. For one of their demos, we decided to test our fluorescent nanoparticles for the first time. 

As soon as we saw our glowing pink nanoparticles skating across the screen in real time, I couldn’t contain my excitement. I jumped up and down like a kid in a candy store. I may have alarmed the sales specialist, because he said, “Ma’am, calm down.” 

Kasey and Alex were just as much in awe. It was one of the coolest things I’ve ever seen next to our live lung imaging. 

Q: Why WVU?

A: The collaboration opportunities here are fantastic. Interactions with  Health Sciences are just amazing. And if I hadn’t decided to come to WVU, I wouldn’t have started looking beyond tumors and venturing into the toxicology field. 

One of my students used to vape and wanted to use our live lung imaging technique to visualize how neutrophils and platelets in the blood vessels of lungs interact with the base components of vape fluid. After short exposures of a couple hours a day for three days, we saw more clumps of neutrophils and platelets staying in vessels for up to 48 hours. 

Other studies have found that when you expose mice to e-cigarette vapor, their neutrophils appear to be dysfunctional, and the mice can’t easily fight infection. So there’s a big question mark, and we need to figure out what’s going on. 

Q: What scientific achievement from history do you wish you could have been there for?

A: I love imaging because I’m amazed by what I can see. I would have liked to be there to see cell movement under a microscope for the first time. Imagine being the first person to see bacteria swimming under a microscope or sperm fertilizing an egg – seeing that come to life.

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