May 22, 2006
Quantum Dots Studied as Intracellular Monitors, Possible Therapeutic Agents
One of the unique features of nanoscale materials is that they are often of the same size as most biomolecules, and thus can be used to study intracellular biochemistry without themselves having much of an impact on normal cellular function. Now, an international team led by investigators at McGill University has taken advantage of the small size of quantum dots to create a nanoscale device that can report on the oxidative conditions within a cell. Moreover, this new type of sensor could serve as a prototype for a therapeutic agent that would use light to generate cell-killing reactive oxygen inside cancer cells.
Reporting their work in the journal Nature Materials, Jay Nadeau, Ph.D., and an international team of collaborators, describe how they modified quantum dots in order to produce a nanoscale object capable of positive from negative electrical charges inside a cell when irradiated with light. The resulting “hole-electron” pair, analogous to the positive and negative charge separation that occurs in doped semiconductor material and that creates transistors, can then do two things – either recombine and trigger the release of bright light or react with oxygen in the cell to produce reactive oxygen that can kill the cell.
Nadeau and his colleagues created this novel type of quantum dot by coating a standard cadmium selenide/zinc sulfide quantum dot with the small organic molecule dopamine, the same molecule many nerve cells use to communicate with one another. Dopamine is an electron donor, which means it is a molecule that under the right chemical conditions will donate an electron to a neighboring molecule. When stimulated by light, quantum dots become electron acceptors, so by combining dopamine with the quantum dot the investigators created a system capable of at least temporarily creating a local positive charge in the vicinity of the dopamine molecules and a local negative charge on the surface of the quantum dot. Charge separation systems such as this are common in biochemical networks and make energy production possible in a cell.
Dopamine plays a second role as well by providing transport into a cell. Many types of cells have dopamine receptors on their outer cell membrane. When these receptors bind dopamine attached to a quantum dot, the receptor drags the entire construct through the cell membrane and into the cell.
Once inside the cell, the dopamine-coated quantum dots are ready to perform as electrochemical sensors capable of reporting on the redox potential of the cell, a measure of its metabolic state. Under so-called reducing conditions, which occur when there is a surplus of electron-donating molecules, light-stimulated dopamine-coated quantum dots luminesce only in the periphery of the cell. As intracellular conditions change from reducing to mildly oxidizing, i.e., when the intracellular redox balance shifts to a slight abundance of electron accepting molecules, the luminescence is visible only in the membrane that separates the nucleus from the cell’s cytoplasm. When the intracellular conditions become fully oxidizing, the modified quantum dots luminesce throughout the cell, including in the mitochondria, which is where cells produce energy.
The researchers note that this system can serve as a model for developing coated quantum dots sensitive to changes in other important intracellular conditions. The investigators also suggest that further study of this type of charge-separation system could lead to a new class of photosensitizers capable of using light to generate reactive oxygen species. In this study, the investigators suppressed reactive oxygen generation in order to study the sensing capabilities of the dopamine-coated quantum dots without damaging the cells.
This work is detailed in a paper titled, “Photophysics of dopamine-modified quantum dots and effects on biological systems.” Investigators from the University of California, Los Angeles, and Argonne National Laboratory also participated in this study. An abstract of this paper it available through PubMed.