Mapping Tumor Heterogeneity With Quantum Dots
One important discovery made about cancer over the past decade is that as a tumor develops, the molecular identity of its cells begins to diverge. As a result, any given tumor is likely to contain groups of cells with differing genetic makeup, growth rates, and more importantly, susceptibility to specific drug therapies. Now, using a mixture of four quantum dots linked to antibodies that can detect cancer-associated proteins, a research team from Emory University has developed a method for mapping the molecular heterogeneity of human prostate tumor biopsies obtained from cancer patients. This method should be applicable to other types of tumors.
Shuming Nie, the principal investigator of the Emory University and Georgia Institute of Technology Center of Cancer Nanotechnology Excellence, led the research team that developed this new method of characterizing tumor biopsies. The investigators reported their work in the journal ACS Nano.
Dr. Nie and his team chose four proteins to target using monoclonal antibodies. To each antibody, they linked a quantum dot—a brightly fluorescent nanoparticle—that emits light with a unique optical signature. After staining human prostate cancer with the four antibody-quantum dot constructs, the researchers used a commercial multispectral imaging system to acquire fluorescence images of the tissue. They then analyzed the raw spectral data with a computer algorithm capable of sorting out the four optical signatures and creating a map of the locations where each of the four quantum dots accumulated on the tumor samples. These maps revealed complex microenvironments within tumors and identified major differences across biopsies from multiple patients.
These maps also pinpointed areas of the prostate gland undergoing structural changes characteristic of healthy tissue becoming malignant. In fact, the investigators note that their work shows that the architectural changes that occur in prostate cancer likely start with a single malignant cell in regions of the prostate gland known as the luminal and basal layers.
This work, which is detailed in a paper titled, "Molecular Mapping of Tumor Heterogeneity on Clinical Tissue Specimens with Multiplexed Quantum Dots,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's Web site.