Northwestern researchers are developing “NanoFlares” that can release a fluorescent signal when they detect cancer stem cells.
Cancer stem cells are thought to be one of the reasons that tumors grow and sometimes return, and they are resistant to chemotherapy.
Researches received a grant two years ago from the National Cancer Institute to study a new way of detecting cancer stem cells in the blood stream.
NanoFlares are engineered particles that integrate DNA and a metal complex. The goal of the 5-year research program is to develop a new method to diagnose cancer earlier.
Dr. C. Shad Thaxton, urologist and assistant professor at Northwestern's Feinberg School of Medicine, and Dr. Chonghui Cheng, assistant professor of medicine at Feinberg, discuss how NanoFlares work and their potential.
What is a NanoFlare and how does it target cells you want to find?
(Cheng) It’s an engineered DNA and metal complex. In the core of the nanoparticle is gold.
(Thaxton) On their surface are DNA sequences that target messenger RNAs in cells. When bound to their target, they release a fluorescent signal. It’s the release of the signal “flare” that leads to the name. If the flare lights up, the target is present. The cells that are lighting up are those of interest. Ultimately, NanoFlares would be added to a blood sample where only the cancer cells would light up, if present.
How do they work?
(Cheng) There are two strands that are attached to the nanoparticles, one of which has a fluorophore [a part of a molecule that can cause fluorescence]. Once you put it into the cell, if it detects an mRNA of interest then it will replace the strand that has the fluorophore. Essentially the fluorophores are free.
What is NanoFlares technology?
(Thaxton) NanoFlares were developed in the laboratory of Dr. Chad Mirkin at Northwestern a few years ago. We're trying to take that technology and adapt it for clinical use. The challenge is to take the technology and translate it into something that is diagnostically useful and clinically meaningful.
Can you tell me about the project? What the focus is?
(Cheng) Currently, the way to identify cancer stem cells is to use antibodies. But, it can be challenging to use antibodies. What we are doing is detecting messenger RNAs. The hope is to develop this nanotechnology, which is most likely more sensitive and robust in terms of identification of CSCs. We want to use cultures to develop the method then move it to human samples hoping that it could be used clinically in the future.
(Thaxton) It is imperative to detect whether or not cells from a primary tumor site have metastasized to a distant site. This greatly impacts patient treatment and prognosis. The technology we’re developing, NanoFlares, may provide an opportunity to detect cancer cells in the blood stream at early time points.
How far along is the research?
(Thaxton) We have demonstrated that NanoFlares can detect and differentiate cancer cells in complex mixtures of cancer and normal cells. Our goal is to begin testing patient blood samples in the next one to two years.
What type of cancer cells are you focusing on?
(Thaxton) Breast cancer. Circulating tumor cells have been most studied in breast cancer and this provides us an opportunity to develop the NanoFlare technology and make reference to prior data and to develop against existing benchmarks. Of course our ultimate goal is to detect the spread of cancer cells in the blood at the earliest possible time point in hopes that with appropriate treatment, patients will do better.
What are cancer stem cells and how do they differ from other stem cells?
(Thaxton) There’s a lot of controversy regarding cancer stem cells, their existence, and their origin. In general, stem cells are few in number and have the capacity to renew their own population as well as give rise to other cell types with more specialized, differentiated functions. The concept of cancer stem cells is that, within a tumor, there are different sub-populations of cells and some of them have the ability to self-renew and also give rise to the more differentiated cell types within the tumor, like stem cells. Importantly, these types of cells are believed to be more resistant to therapy, thus detecting them in the primary tumor or in the blood is believed to be critical for identifying new and appropriate therapies.
(Cheng) Sometimes after several year patients come back because the tumors have come back and their tumors are thought to have rose from these cancer stem cells. The cancer stem cells are the ones that are resistant to chemotherapy. They do share some stem cells properties like renewal and differentiate. CSCs are not the same as the stem cells that people are using nowadays
Where do cancer stem cells come from?
(Thaxton) There are different opinions here, too. In general, though, some believe that they’re the primary cell that drives the formation of the tumor. On the other hand, some evidence suggests that they’re actually formed as the tumor evolves.