In the world of biological imaging, there are few technologies that can crisply capture structure (of a body part or tumor, for instance) and molecular detail at the same time — especially in a live animal. But scientists in the lab of Adam de la Zerda, PhD, assistant professor of structural biology, have married a well-established imaging technique with tiny prisms of gold to capture both anatomy and molecular details.
The result: something of an extraordinarily powerful magnifying glass. It's a microscope that can image its immediate surroundings, like a swath of skin, in extreme detail — down to a single cell— and the technique can even be used to answer specific questions about a cell's molecular makeup.
The foundation of the new technique is called optical coherence tomography, or OCT for short, and it's used to image structures at close range, like skin tissue, or vessels within a range of a couple of millimeters. Currently, it's the go-to imaging technique for ophthalmologists checking up on parts of the eye, like the retina, and it's often used to understand the composition of skin cancers.
"Our goal is to take this existing technology, enhance it, and expose it to the whole world of molecular imaging," said de la Zerda. "So instead of just being able to see the anatomy, we'd also able to start asking questions about its molecular status, like if tumor cells show signs of metastases."
With the help of gold nanoprisms, de la Zerda and his lab have found a way to do just that. The nanoprisms' refractory properties enhance the detail of what OCT is able to capture, sharpening the image and picking up new details, too.
de le Zerda and Peng Si, PhD, postdoctoral research fellow, first demonstrated the technique by imaging blood vessels and melanoma tumors in a mouse's ear: Regular OCT showed an intricate web of vessels, all forking in different direction. But with the addition of gold nanoprisms, a scan of the same area was nearly opaque with vessels, revealing a huge number of blood conduits that hadn't been seen before.
On top of that, the minute gold flecks are also "programmable," meaning that de la Zerda can stick little molecules onto the gold particles that will act as trackers. Inside the body, these markers have specific properties, enabling them to selectively bind to certain cells of interest, which show up on the OCT scan.
Between the unique optical and biological features of the nanoprisms, their synthesis is no easy feat.
"Aside from maintaining the size and shape of the particles you also need to make sure they have the right biological properties, so that they're stable in the blood, nontoxic and programmable," said Si, who led the creation of the nanoprisms. "It took me several months to optimize them."
The tactic could one day be very helpful in differentiating between metastatic and non-metastatic tumor cells.
A paper describing this imaging technique was published in ACS Nano. Si is the first author.
de la Zerda sees the hybrid technique as a potential step for assessing cancer drug efficacy. "Not all of the cells in a tumors are molecularly the same — some may respond differently to a treatment, and some may not respond at all," said de la Zerda. "If a doctor administers a treatment, and 90 percent of the cells respond favorably, it will look like the tumor is shrinking. But in reality, there's an aggregate of thousands of cells that are going to come back."
This new form of OCT could ideally sniff out those remaining cells and reveal their resistance. "And then, theoretically, doctors could give the patient another treatment that would wipe out that last remaining percentage of cells," said de la Zerda.
It's not an application that can be used for everything, says de la Zerda, but for instances that require imaging of relatively thin tissues, it could be a big advance.
Currently, the technique is only being used in mice, as the gold nanoparticles would still need to be approved by the FDA for use in humans.
"We want to start using this technique to track the growth of tumors and see each and every cell, in a mass of a million cells, to better understand how tumors grow and even how cells separate from the mass and travel to other parts of the body," said de la Zerda.
Image by James Strommer