Using a synthetic peptide modeled after the protein that the human immunodeficiency virus (HIV) uses to enter cells, a multi-institutional research team has created quantum dots that can penetrate the cell membrane and image internal structures in a cell.
This research team has also used peptide-coated quantum dots to monitor enzymatic activity within a cell.
In papers published in the journal Bioconjugate Chemistry and Nature Materials, researchers at the U.S. Naval Research Laboratory, Johns Hopkins University, and The Scripps Research Institute reported on their studies of developing a general method for creating self-assembled peptide-quantum dot conjugates for use in a variety of biomedical research applications. Their method involves two key steps. The first step is to create quantum dots and then coat them with the molecule dihydrolipoic acid (DHLA), a biocompatible, water-soluble molecule. The second is to attach a short peptide composed entirely of the amino acid histidine to one end of a larger peptide with a specific application, such as targeting. Poly(histidine) binds tightly to DHLA, so that when a poly(histidine)-modified peptide and DHLA-coated quantum dots are mixed the two components self-assemble into a sturdy nanosized particle.
To demonstrate the utility of this method, the researchers developed two different quantum-dot based research tools. In one application, the researchers created multiple colors of cadmium selenide quantum dots coated with TAT, the peptide that HIV uses to enter human cells. They then used these peptide-quantum dot conjugates to study how quantum dots move inside cells as a model for gaining a better understanding of nanoparticle trafficking within cells. The researchers note that this proof-of-principle experiment suggests that it should be possible to use this self-assembly process to create multifunctional quantum dots coated with more than one peptide, or to use uniquely colored quantum dots, each coated with a different peptide, to image multiple functions within a single cell.
In a second demonstration, the investigators used several different peptides to detect and quantify the activity of four different proteases using fluorescence energy resonance transfer (FRET). Proteases are enzymes that degrade specific proteins and measurements of protease activity are used to identify some types of malignant cells.