Cancer Nanotechnology: an overview of INBT's 2011 symposium talks

Stephen Baylin

Nanoparticle driven cancer treatment is a popular, and obviously important topic in cancer nanotechnology. Maitra touched on a couple of the strategies his team has developed. Through a mechanism known as desmoplasia, efficacy of Placitaxel was greatly improved with Maitra's albumin functionalized nanoparticles. Desmoplasia is the process of "stromal depletion" Maitra said and it was recently found to be an active process that can be initiated through binding of albumin to SPARC, a receptor commonly found on pancreatic stromal cells. The stromal breakdown allows for much greater nanoparticle transport to cancer cells "by removing the physical barrier" the stroma presents, said Maitra. Maitra also discussed another part of his work involving inhibition of the hedgehog pathway to suppress basal cell carcinoma. Maitra showed an image of a patient from a clinical trial with lesions all over the body and after treatment with hedgehog inhibitor GDC449, the lesions all vanished. However, this same patient and many others from the study relapsed due to what Maitra believed to be a "secondary mutation." Maitra hopes to now find a way to bypass this "evolutionary response" and permanently remove these cancerous lesions. Maitra's research includes a host of nanoparticle based approaches personalized for different types of cancer with hopes that specificity will eliminate unnecessary side effects and improve treatment overall. (Gregg Duncan)

Greg Longmore highlighted the sad reality about cancer: it's rarely the primary tumor that kills someone, but 90 percent of the time it's the metastatic spread. Thus, his research has sought to understand how tumors evade tissue and the genetic cues the invasive cells give one another to invade the epithelium, which is the barrier that lines glands and surface structures of the body. "Understanding this process is critical to maintaining tumor dormancy and for treating metastatic disease," he said. His laboratory has also focused on development and the similarities between normal tissue growth and the spread of cancerous cells throughout the body. (Jacob Koskimaki)

Once objects are shrunk to sizes comparable to the wavelength of light, interesting optical phenomena can be observed and Pomper has been exploiting this with nanoparticles and molecules for high resolution imaging for cancer. Molecular imaging with "picomolar sensitivity," Pomper said, would be ideal for early detection of cancer where small numbers of cancerous cells are present, or even down to imaging genes. A cationic nanoparticle functionalized with a gene able to identify the PEG-Prom gene, which has been shown to be upregulated in cancer cells, was developed to allow for cancer cell specific imaging. This could allow for physicians to tell the difference between inflammation and early tumor formation. Pomper mentioned that one reviewer of a paper he submitted wanted to know how his imaging techniques compared to the current medical standard. It was clearly seen from images of a patient with breast cancer, only the cancerous areas were highlighted with Pomper's nanoparticle-based imaging while the whole breast was tagged with a standard SPECT image. Pomper also discussed a new therapeutic agent his group had been researching the [131I] FIAU "hand grenade." This radioactive isotope is a beta-particle emitter that could be initiated at the site of a tumor that could drastically reduce the negative side effects with typical radiotherapies. Pomper's work has shown how moving down to the nano-regime for imaging could greatly increase diagnostic capabilities for cancer where early and accurate detection is key. (Gregg Duncan)

Denis Wirtz jokingly apologized for not having cells to show in 3D “like Pixar,” but he had a strong message about the importance of understanding how cells move and the ways his lab is facing the challenge of studying cell motion in three dimensions. Metastasis is the relocation of malignant cancer cells from the original tumor to another part of the body where they take root and cause more disease, and it is often the aspect of cancer that is most deadly. To understand metastasis, scientists probe underlying functions: how cells attach to the surfaces of other cells or the extracellular matrix, how cells are cued to migrate, how they accomplish a movement. Most commonly, scientists study cell motion on two-dimensional surfaces. This makes experiment design and imaging the cells fairly straightforward, but it is not very realistic for most types of cells. “Cells encounter an intrinsically 3D space” in the tissues of the body, said Wirtz, and his lab has taken on the challenge of experimentally simulating that. Using new techniques to observe cells moving within a material and upon a surface, researchers in the Wirtz Lab have found that features that are present in 2D situations, such as clear attachment points between the cells and the surface, don’t have obvious analogues in the 3D situation. They found, however, that cells move by sending out protrusions of their membranes through the material, and how fast they could move depends on how much the protrusions branch. To accomplish this research, the researchers in the Wirtz Lab refined a technique called reflection confocal microscopy and were able to analyze cell motion by tracking how the cell deformed the material around them. This research can help us understand how malignant and highly mobile cells move through the tissues of the body. (Dan Richman)

We know from experience with certain infectious disease vaccines that vaccination is a way to get the body to improve its own ability to fight disease. Vaccines can also be used to fight cancer by conditioning the immune system to recognize tumor cells as disease cells and target them for destruction. In Hy Levitsky’s lab, researchers are increasing the efficacy of tumor vaccine by carefully tracking how well the vaccine gets to the right immune cells in the body. In order to start targeting tumors, immune cells have to “learn” about the tumor cells by being presented with a marker for the cell called an antigen. Therefore, the vaccine that is injected into the body contains parts of tumor cells. In addition, the vaccine contains what are called adjuvants, which are substances that enhance the delivery of the antigen to the immune system. In order to track how different adjuvants affect the delivery of the antigen, Levitsky’s lab includes a chemical label in the vaccine that shows up in magnetic resonance imaging (MRI). Since the label, adjuvant, and antigen are absorbed together by cells in the body, imaging the location of the label allows the delivery of the antigen to be monitored. The Levitsky Lab used the technique to show that using a certain adjuvant along with a tumor cell antigen increased the number of immune cells in mice that picked up the antigen and moved to a lymph node to present it to other immune cells that would target a tumor. This research evaluated the effectiveness of a particular adjuvant to improve vaccine delivery and also demonstrated a new technique to track vaccine delivery in general. (Dan Richman)

How do cells sense the environment and make a response if needed? The question has driven Jin Zhang's research. "Cells use very smart strategies to regulate signaling," she said. For instance, calcium is an important signaling molecule that drives insulin secretion, but its activity is regulated by another molecule called PKA (protein kinase A). Exactly how these two molecules coordinate a response to finely-tune insulin secretion has eluded researchers. Her laboratory has used a fluorescent probe to track the response of PKA to generate a model of calcium and the PKA response, including spatial and time-inclusive data. She hopes her research will create more targeted treatments to help regulate this process in cells. (Jacob Koskimaki)

Gregg Duncan is a pre-doctoral fellow in Chemical and Molecular Biology conducting research in the >Michael Bevan Lab at the Whiting School of Engineering.

Jacob Koskimaki is a pre-doctoral fellow in Biomedical Engineering conducting research in the Aleksander Popel Systems Biology Lab at the Johns Hopkins School of Medicine.

Dan Richman is a pre-doctoral fellow in Physics conducting research in the Blake Hill Lab, Department of Biology, Krieger School of Arts and Sciences

All three are Integrative Graduate Education and Research Trainees (IGERT) supported by INBT and the National Science Foundation.

Mary Spiro is INBT's Science Writer