Expanding quantum dot utility in cancer diagnosis and treatment

Jun 28 2009

Quantum dots (QDs), nanoparticles that shine with extraordinary brightness when excited by light energy, have shown promise as new tools for detecting cancer at its earliest appearance, but concerns about potential toxicities have limited their clinical development. Researchers at the University of Buffalo may have found an answer to this limitation with their development of a new way to create QDs.

Their work comes at an opportune time, because a team of investigators from the University of Texas at Arlington (UTA) has shown that QDs can function as nanoscale thermometers to guide the numerous nanoparticle-based thermal therapies being developed to treat cancer.

Paras Prasad, Ph.D., principal investigator of the National Cancer Institute Cancer Nanotechnology Platform Partnership based at the University of Buffalo, has been developing a variety of methods for creating novel types of QDs. His most recent work, published in the journal Small, has yielded biocompatible QDs that produce no toxic effects for more than 3 months after injection. The new QDs contain a cadmium sulfide core surrounded by a thin shell of cadmium, selenium, and tellurium similar to standard QDs. However, as a finishing touch, the researchers added a rugged, water-repellant coating that prevents any of the potentially toxic metals in the QDs from leaching into the body. This coating also contains chemical groups to which targeting agents or drugs can be attached.

When these QDs are injected into mice, Dr. Prasad and his colleagues were able to image these exceedingly bright nanoparticles using near-infrared spectroscopy and determine where they accumulated in the body. Unlike standard QDs, these coated nanoparticles were less likely to accumulate in the liver and spleen. Further examination of tissues removed from the mice 100 days after injection showed that there was no tissue or cellular damage associated with QD accumulation. The researchers also report that the injected animals showed nothing but normal behavior over the duration of the study.

Meanwhile, Bumsoo Han, Ph.D., and UTA colleagues report in the Annals of Biomedical Engineering that they have used cadmium telluride/zinc sulfide QDs as nanoscale thermometers capable of measuring local changes in temperature in real time. The goal of this work is to create a measurement tool that will enable oncologists to determine whether thermal anticancer therapy is producing cell-killing temperatures throughout each treated tumor.

The operating principle for this work is that QD emissions are sensitive to the local temperature. When QDs are administered to a target tissue prior to thermal therapy, they can give a pretherapeutic reading of a temperature surrounding a tumor. During therapy, QD emissions then can be monitored to ensure that all of a tumor, including its outer edges, reach a temperature that ensures cell death. Indeed, the investigators showed that the QDs can produce a temperature map with spatial resolution that can clearly reveal those regions of tissue that have become hot enough to produce cell death.

Dr. Prasad's work, which is detailed in the paper "Biocompatible near-infrared quantum dots as ultrasensitive probes for long-term in vivo imaging applications," was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's Web site. View abstract

Dr. Han's work is detailed in the paper "Development of quantum dot-mediated fluorescence thermometry for thermal therapies." Investigators from the UT Southwestern Medical Center in Dallas also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract