May 15, 2006
Nanomaterials Advance Early Cancer Detection Methods
There is little doubt that early detection of cancer is one of the keys to achieving a positive outcome for cancer therapy, and many cancer researchers believe that nanotechnology will play a critical role in improving oncologist’s ability to find cancer in its earliest and most treatable stages. Now, two groups of investigators have in fact developed nanoscale devices that with further refinement could lead to more sensitive diagnostic assays for early-stage cancer.
Reporting its work in the journal Bioconjugate Chemistry, a multi-institutional team of investigators describes its work developing nanoporous glass beads to harvest the trace proteins in blood that may represent a molecular fingerprint of early stage cancers. This team was led by Paul Hermann, M.D., Ph.D., at the National Cancer Institute; Lance Liotta, M.D., Ph.D., and Emanuel Petricoin III, Ph.D., formerly at the National Cancer Institute and now both at George Mason University; and Mauro Ferrari, Ph.D., formerly at the Ohio State University and now at University of Texas Health Science Center at Houston.
There are many highly sensitive techniques, such as mass spectrometry, that are available for accurately determining the identity of disease-related proteins. Indeed, cancer researchers have been attempting to use these techniques in an effort to identify protein patterns that would indicate that cancer is present even before a tumor grows to a physically detectable size. But these techniques have fallen short of the mark, not because of limitations in the identification methods, but because it has proven challenging to collect and separate the proteins that are present in blood in small amounts – the very proteins that researchers have assumed will have diagnostic value.
To overcome this problem, the investigators turned to nanoporous glass beads. These beads were engineered to contain nanoscale pores capable of trapping blood-borne proteins. These materials act like selective sponges, soaking up only those proteins that can fit inside the pores. Tailoring the size of the pores, the investigators found, affords a set of materials that can collect subsets of the proteins in blood. These proteins can then be recovered from the collection devices and identified using mass spectrometry. The investigators believe that this new method, combined with advanced bioinformatics techniques, will enable them to correlate specific patterns of harvested proteins within initial stages of cancer and other diseases.
In a second study, published in the journal Analytical Chemistry, a team at the University of Florida, led by Weihong Tan, Ph.D., used aptamer-labeled magnetic nanoparticles to collect and detect small numbers of leukemia cells in blood. Aptamers are small pieces of synthetic RNA or DNA that are designed, much like antibodies, to bind tightly to specific biomolecules, such as the proteins found on the surfaces of malignant cells.
In experiments discussed in their current paper, the investigators created an aptamer that binds specifically to an as-yet unidentified protein on the surface of leukemia cells. They then linked this aptamer to magnetic nanoparticles and to silica nanoparticles that also contain fluorescent dye molecules. The investigators used the magnetic nanoparticles to bind to leukemia cells and separate them easily from other cells in whole blood using a commercially available magnetic cell-sorting instrument. The fluorescent nanoparticles provided a sensitive marker for counting the separated cells using fluorescence imaging. The researchers note that using both nanoparticles simultaneously results in a targeted cell collection and identification technique that would not have been possible using either of the nanoparticles alone.
The work on selective protein isolation, which was funded by the National Cancer Institute, is detailed in a paper titled, “Fractionation of serum components using nanoporous substrates.” Investigators from the FDA-NCI Clinical Proteomics Program also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website.
A second paper on this work, titled “Nanoporous surfaces as harvesting agents for mass spectrometric analysis of peptides in human plasma,” also appeared in the Journal of Proteome Research. An abstract of that paper is available through Pub Med.
The work using aptamer-targeted magnetic nanoparticles, which was funded in part by the National Cancer Institute, is detailed in a paper titled, “Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells.” An abstract of this paper is available through PubMed.