What do you do with undergraduate degrees in bioengineering and German? Allison Dennis, assistant professor of biomedical engineering and of materials science and engineering, won a Fulbright and went to Germany, of course. She had planned to build scaffolds for engineering bone tissue, but her advisor steered her into making gold nanoparticles for drug delivery. “That’s how I got into bionanotechnology,” she says, “and I haven’t looked back since.”
Dennis makes and studies tiny, quirky particles called quantum dots—materials that glow different colors under UV light depending on their size. Engineers use quantum dots for many applications, from television screens to chemical sensors. Dennis uses them in biotechnology. In one major project, she is collaborating with Darren Roblyer, an assistant professor of biomedical engineering, and Sam Thiagalingam, an associate professor of medicine, to track breast cancer tumors and see how well chemotherapy is working, so “we can design treatments that adapt as the tumor evolves,” she says. A big challenge: most quantum dots are made from a rogues’ gallery of toxic metals like cadmium, arsenic, lead, or mercury. Dennis wants to find non-toxic alternatives to use in people.
BU Research spoke to Dennis about the past and future of quantum dots and how her work may help revolutionize breast cancer therapy. The conversation has been condensed and edited.
BU Research: What are quantum dots?
Dennis: If you take any semiconductor metal and reduce it to a nanoparticle size, about 2–10 nanometers in diameter, it takes on all these really interesting properties. What we are most interested in is the fact that it fluoresces—if you put these particles under a black light, they light up like a Christmas tree. And the only thing different among the different colors is the different size of the particle. So, the exact same material, just a different size, gives you different colors.
That doesn’t make any sense to normal people.
Right, it’s pretty unique and beautiful.
Can you give me an example of a material you use?
Cadmium selenide—it’s actually in TVs on the market already.
Okay, so you take a chunk of it and you make it—how small?
A nanometer is one-billionth of a meter.
And it turns a color?
Yes. There are only 100 to 10,000 atoms in the particle, so it’s very, very small. And if you make it a little bit bigger, it’s red. If you make it a little bit smaller, it’s blue. In the middle, it emits green. And so it’s just literally a rainbow based on the size of the particle.
Why does this happen?
This is all quantum mechanics. We live in a world with traditional mechanics, where if you throw a ball up, it will come back down. This is quantum mechanics, and so now we’re talking about energy levels, the confinement potential of the excited electron, all these different things. And what I really love about quantum dots is, it’s a way to visualize quantum mechanics in real life; that just by changing the size, we can see different energies in the form of different colors. If the particles are very small, the energy is very high, and that’s why it’s blue. If the particles are a little bit larger, then the energy is a little lower and that color is more red. Energy and color correlate.
When did people start playing around with quantum dots?
Colloidal quantum dots (quantum dots like I use, where the particles are in solution) were hypothesized and then synthesized in the 1980s and ’90s. They were first used for biomedical applications in the late ’90s, early 2000s. You can put them in cells and label, say, four or five different parts of the cell and excite them all with UV light and look at these different colors. We are interested in doing that same kind of multiplexed imaging in tissues, using deep red and near-infrared wavelengths to get some tissue penetration and see deeper through tissue. So we’re developing some new particles. We make heterostructures, which means you have one semiconductor core and a second semiconductor shell. Sometimes we put a second shell on top. So we’re working with multiple materials, combining them in unique ways. And that’s how we get these interesting optical properties that haven’t been made in 20 years of quantum dot chemistry.
How would you use them?
One big project idea we have is the molecular phenotyping of breast cancer. Often in breast cancer, you’ll receive chemotherapy, the tumor will regress, and the therapy appears to be working. But then there’s a rebound afterwards. And often, that recurrence is not sensitive to the same chemotherapeutics that were originally given; they’re chemo-resistant. And it turns out that that happens because a tumor is almost always heterogeneous—it’s not all identical cells in that tumor. And so when we treat some of those cells, 95 percent of them may die, but a couple survive, and now they have all the resources because they’re not crowded out by the rest of the tumor, and they rebound and grow back.
Yeah, I agree. But these different cells within the tumor might have different susceptibilities to other chemotherapeutics. We already know a handful of different receptors that are relevant for breast cancer. HER2, for example; folate receptor; CXCR4 is one that can indicate a metastatic breast cancer. And so the goal is to tag these various receptors with different colors of the particles. And if we can track, over time and space, the different cell types and which chemotherapeutics might work in those cells, we can design treatments that adapt as the tumor evolves.
What are the biggest challenges ahead in your field?
Finding high-quality materials in the near-infrared is an ongoing challenge. High-quality non-toxic materials in the near-infrared is a doubly hard challenge. So that’s certainly a place where I believe our chemistry toolset can really have an impact.