August 28, 2006
Enzyme Modulates Quantum Dot Uptake By Cells
Brightly fluorescent quantum dots are proving to be powerful tools for tracking the motion of cells and molecules, but their usefulness has been limited by the difficulty in getting these nanoscale beacons inside cells in a directed, controlled manner. A new simple and versatile method appears to overcome this limitation by using a specific type of enzyme to facilitate quantum dot entry into cells.
Reporting its work in the journal Nano Letters, a team of investigators led by Jianghong Rao, Ph.D., a member of the Center for Cancer Nanotechnology Excellence Focused on Therapy Response, at Stanford University, describes its use of matrix metalloproteases (MMPs) to modulate cellular uptake of quantum dots. MMPs, a family of enzymes that degrade the extracellular matrix that holds cells together, are involved in metastasis and tumor invasion.
The investigators constructed quantum dots coated with two short peptides, one that can trigger cell uptake and the other that blocks cell uptake but is the preferred substrate for one particular MMP known as MMP-2. When added to cells growing in culture, the doubly labeled quantum dots were unable to enter cells. But when the investigators added MMP-2, the quantum dots were transported rapidly into the cells. The researchers obtained the same results using a peptide that is the preferred substrate for a second MMP, known as MMP-7.
In addition to providing a versatile method for modulating quantum dot uptake by cells, these MMP-activated quantum dots could yield a new tool for imaging MMP activity in the body, since these quantum dots would only be taken up by cells expressing MMPs on their surface. The investigators note that this strategy could also be used to target the delivery of drug-containing nanoparticles to tumor cells overexpressing MMPs.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Protease-modulated cellular uptake of quantum dots.” This paper has been published online in advance of print publication. An abstract of this paper is available at the journal’s website.