Researchers at the Massachusetts Institute of Technology in Cambridge and Beth Israel Deaconess Medical Center in Boston have developed a new procedure that produces ultra-compact quantum dots with a coating that does not impair the superior optical properties of the dots and makes them suitable for in vivo imaging, according to a study published in the November online issue of Journal of the American Chemical Society.
Quantum dots have shown promise in a variety of imaging and therapeutic applications, particularly when they are coated to render them biocompatible, however, such coating can increase the size of quantum dots significantly, adversely effecting their pharmacokinetic and biodistribution properties, according to Moungi Bawendi, PhD, a member of the MIT-Harvard Center of Cancer Nanotechnology Excellence, and co-author of the study.
To create these ultra-small quantum dots, Bawendi and co-author, John Frangioni, MD, PhD, created dual-layer nanocrystals with a zinc-cadmium-sulfide (ZnCdS) core surrounded by a cadmium selenide (CdSe) shell. Bawendi said combination of materials creates a compact yet bright quantum dot.
Researchers then added a coating of cysteine, a sulfur-containing amino acid that binds tightly to the CdSe shell. When stored in the presence of a reducing agent, these quantum dots are stable for one week at room temperature and at least three months at 4 degrees Celsius. Dynamic light scattering, a technique used to study nanoparticle size, showed that the diameter of these quantum dots was 5.9 nanometers. More importantly, their size did not increase when incubated with serum, demonstrating that the cysteine coating prevented proteins from collecting on the quantum dot surface, said Bawendi and Frangioni.
Both Bawendi and Frangioni noted that the exceptionally small size of the quantum dots and their stability in serum led to new in vivo behavior. When injected into rats, the majority of the quantum dots accumulated in the bladder within four hours, demonstrating that these nanoparticles are small enough to be filtered out of the kidneys.
The results suggest that these compact quantum dots, if attached to a small targeting molecule, could be used “to image tumors without having to worry about accumulation within the body. Moreover, the ability to directly conjugate to QD-Cys opens up the possibility of functionalized nanocrystals for in vivo targeted imaging, in which small targeting molecules can be appended to QD-Cys, and unbound QDs can be rapidly cleared to achieve high signal/noise ratios and to reduce background toxicity,” according to Bawendi and Frangioni.