Using a quantum dot plus an aptamer that doubles as a tether for the anticancer drug doxorubicin, a team of investigators at the Massachusetts Institute of Technology (MIT)-Harvard Center of Cancer Nanotechnology Excellence has developed a multifunctional nanoparticle that not only treats cancer but also images those tumors that have received drug therapy. The researchers report their work in the journal Nano Letters.
Omid Farokhzad, M.D., Harvard University, and Robert Langer, Ph.D., MIT, led the team of investigators that developed this multifunctional construct. The researchers built this construct by first coating a quantum dot with an RNA aptamer designed to recognize and bind tightly to prostate specific membrane antigen (PMSA), a surface marker found on prostate tumors. They then incubated this coated quantum dot with doxorubicin, which integrates, or intercalates, itself within the highly folded structure of the aptamer. The investigators showed that doxorubicin intercalation had no effect on the ability of the aptamer to bind to PMSA.
Quantum dots are well known for their ability to emit light of well-defined color. In this experiment, the investigators chose a quantum dot with light in the range of 470 to 530 nanometers (nm). Doxorubicin, aside from being a potent anticancer agent, also absorbs blue light efficiently, with maximal absorption at a wavelength of 480 nm, and then emits light that spans the green-to-orange portion (520-640 nm) of the visible light spectrum.
When the quantum dot and a doxorubicin molecule are close to one another, as they are in this construct, the two optically active systems interfere with one another, greatly suppressing any light emission from either of them. Indeed, when the investigators incubated the quantum dot-aptamer-doxorubicin construct with PMSA-expressing prostate cancer cells, they were able to detect only minimal light emission. However, 90 minutes later, the investigators detected bright optical signals from both the quantum dot and doxorubicin, resulting from the fact that the construct had released doxorubicin into the treated cells.
This work, which was funded by the NCI’s Alliance for Nanotechnology in Cancer, is detailed in the paper “Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer.” Investigators at the Gwangju Institute of Science and Technology in South Korea also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.