March 6, 2006
Protein Nanocages Target Melanoma Cells
Using a nanoscale protein cage capable of entrapping small molecules, researchers at Montana State University have created a novel nanoparticle that can efficiently target the rapidly growing blood vessels that surround tumors. Engineered protein cages hold promise as nanoscale delivery devices because they are precisely defined structures that are relatively easy to mass-produce. The results of this effort have been published in the journal Chemistry & Biology.
A research team headed by Montana State colleagues Trevor Douglas, Ph.D., and Mark Young, Ph.D., chose to work with a heat shock protein isolated from bacteria that thrives at high temperature. The investigators had previously shown that this protein, which consists of 12 subunits that self-assemble into an empty 12-nanometer diameter cage, could be readily manipulated using both chemical and genetic modifications without affecting its integrity or size.
Using genetic techniques, the researchers produced a version of the protein that carried a specific peptide on the nanocage surface. This peptide, known as RDG-4C, binds to proteins known as αvβ3 and αvβ5, molecules that appear on tumor cells during angiogenesis, the process that tumors trigger to produce new blood vessels. The researchers also attached 26 fluorescent dye molecules to each nanocage using a chemical linker, producing a targeted imaging agent for angiogenesis.
The researchers then added the multifunctional nanocages to cultured melanoma cells that express the αvβ3 protein. Using standard fluorescence microscopy, the investigators were able to show that the nanocages bound efficiently to the melanoma cells. The researchers were then able to separate the melanoma cells bound to the fluorescent nanocages from other cells using a standard fluorescence-based cell sorter. Similar results were obtained when the investigators replaced the small RDG-4C peptide with a much larger monoclonal antibody that also targets αvβ3.
This work is detailed in a paper titled, “Melanoma and lymphocyte cell-specific targeting incorporated into a heat shock protein cage architecture.” An abstract of this paper is available through PubMed.