February 5, 2007
Bright Nanoparticles Aid Basic Cancer Biology Studies
Though there is little doubt that nanoscale devices are going to play a critical role in improving cancer detection and treatment over the next five to ten years, nanoparticles are already having a major impact on the way that cancer biologists study the processes that go awry within malignant and metastatic cells. By taking advantage of the unique optical and other physical properties of nanoscale materials, researchers have created a veritable toolbox of nanoparticle probes that can track the fate of cells and even individual molecules in complex environments, opening the door to a wide range of new experiments designed to better understand the cancer process.
Three recent papers highlight the types of new nanoscale materials that chemists and engineers are developing to aid their cancer biologist compatriots. Xiaogang Peng, Ph.D., and his colleagues, reporting their work in the journal Nano Letters, have developed bright, water-soluble, cadmium-free quantum dots that remain brightly fluorescent even after 25 days of irradiation with a laser.
These new quantum dots are made by adding small amounts of manganese to the zinc sulfide and zinc selenide used to form the fluorescent nanocrystals. Adding a 2-3 atom-thick layer of zinc selenide to the outside of these quantum dots enabled the researchers to add a thin coating for sulfur-containing molecules that render the nanoparticles soluble in water without adversely affecting the nanoparticles’ bright fluorescent emissions.
The sulfur groups also provide a site for attaching targeting molecules and other biochemical probes useful in cell biology studies. In this paper, the researchers showed that they could attach the biomolecule avidine to the nanocrystals and use it to visualize the molecule biotin, to which avidine binds tightly. The researchers note that as with conventional cadmium-based quantum dots, they can tune the optical properties of these quantum dots by changing the chemical conditions used to make these nanoparticles.
In another paper published in Nano Letters, A. Paul Alivisatos, Ph.D., and colleagues at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory, describe their development of quantum rods that are even brighter than spherical quantum dots. The rods, which range from 2 to 10 nanometers in diameter and 5 to 100 nanometers in length, can serve as molecule-sized labels for biological research whose color is determined by the exact dimensions of a particular quantum rod.
In their native form, quantum rods are relatively inert and insoluble in water, making it difficult to modify them with biological targeting agents and use them as biological labels. Alivisatos and his collaborators solved this problem by depositing a thin film of a silicon-containing compound known as a silane. The investigators then showed that the resulting silane-coated quantum rods, which were stable in water for over two years, were biocompatible, water-soluble, and easily modified with targeting agents.
In one experiment, the investigators labeled a quantum rod with a monoclonal antibody that recognizes the breast cancer biomarker known as HER2 and used it to detect HER2 on the surface of cultured HER2-positive breast cancer cells. In another experiment, the investigators were able to track individual quantum rods as they traversed the inside of a cultured breast cancer cell.
Taking a different approach to biomolecule tracking using nanoparticles, Brahim Lounis, Ph.D., and his colleagues at the University of Bordeaux in France have used gold nanoparticles as long-lived probes of biomolecules in cell membranes. The results of this study appear in Biophysical Journal.
Lounis and his collaborators were interested specifically in designing a nanoprobe for tracking molecular motion in the normally fluid cell membrane without interfering with normal membrane function. To track the gold nanoparticles, the researchers used a technique called photothermal spectroscopy, which can detect the small amount of heat that gold nanoparticles emit when irradiated with light. This measurement technique, which the investigators refined for use with gold nanoparticles, enabled the unprecedented detection of individual 1.4-nanometer gold particles in live cells. Furthermore, they were able to make video recordings of the nanoparticles attached to individual proteins in the cell membrane.
The work with cadmium-free quantum dots is detailed in a paper titled, “Efficient, stable, small, and water-soluble doped ZnSe nanocrystal emitters as non-cadmium biomedical labels.” This work was published online in advance of print publication. An abstract of this paper is available at the journal’s website.
The work with quantum rods is detailed in a paper titled, “Semiconductor quantum rods as single molecule fluorescent biological labels.” This work was published online in advance of print publication. An abstract of this paper is available at the journal’s website.
The work with gold beads is detailed in a paper titled, “Single nanoparticle photothermal tracking (SNaPT) of 5-nm gold beads in live cells.” An abstract of this paper is available through PubMed.