Quantum Dots for Early Disease Detection
Research from the lab of Prof. Ken Roberts
This research project centers on utilization of highly luminescent semiconductor nanoparticles known as quantum dots (QD) as new diagnostic (biomonitoring) indicators of early-stage disease in living cells. In comparison to organic molecules traditionally used as diagnostic indicators, QDs have 20 times enhanced luminescence and 100 times enhanced stability. In addition, a unique property of QDs is that their emission wavelength (color) changes as a function of the QD’s size. For example with CdSe/ZnS QDs, 2.8 nm diameter QDs luminesce green, while 3.4 nm dots luminesce yellow, and 5.6 nm dots are red. Therefore, by conjugating different size/color QDs with different bioconjugates (e.g., antibodies) multiple addressing of intracellular targets can be monitored in the same assay with the same excitation source, which is crucial for real-world analyses where sample amounts are often limited. However, for QDs to be practical a well-designed method needs to be developed to allow for biocompatibility of the QDs; first by chemically functionalizing the ZnS shell of the QD, followed by streptavidin-biotin attachment of antibodies that will selectively target intracellular components. Once the cellular target has been labeled by the quantum dot conjugate, laser-induced fluorescence, confocal microscopy, and Raman spectroscopic tools will be used for detection and imaging. In particular, studies within this proposed research will focus on investigation of deleterious DNA nucleobase modifications that have the potential to ultimately lead to cancer. Research efforts directly related to the use of QDs to detect pre-carcinogenic DNA are nonexistent, and abundant success can be envisioned. In addition to DNA modifications, concurrent spectroscopic investigation of the in vivo uptake of bioconjugated QDs will be performed. The first intracellular targets will be carcinogenic DNA adducts of catechol estrogen quinone and dibenzo[a,l]pyrene diol epoxide as related to breast and lung cancer, respectively.