New Coating Enables Quantum Dots To Penetrate Cells
In just the few years since their discovery, quantum dots have become an important tool for imaging events occurring on the outside of cells and for identifying specific molecules in "fixed" cells. Researchers have found it difficult, however, to use quantum dots for molecular imaging inside of living cells, largely because these fluorescent nanoparticles tend to clump together inside organelles such as endosomes and lysosomes. But by using a positively charged polymer coating, investigators at the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology have developed quantum dots that penetrate the cell membrane, break open endosomes and lysosomes, and avoid clumping.
Reporting its work in the Journal of the American Chemical Society, a team led by Shuming Nie, Ph.D., describes its use of a composite polymer made from poly(ethylene glycol) (PEG) and poly(ethylene imine) (PEI) as a biocompatible coating for quantum dots. This PEG component makes the quantum dots water soluble, while the PEI component provides three important properties to the quantum dots. First, the coated quantum dots do not aggregate, since each positively charged quantum dot repels all other positively charged quantum dots. Second, PEI moves easily across the cell membrane, and thus, so do the quantum dots. Finally, the positive charge on the PEI component soaks up protons in the acidic environment of an endosome, which has the net effect of disrupting the endosome membrane and allowing the coated quantum dots to escape into the cell's cytoplasm.
Fluorescence imaging experiments were able to track the coated quantum dots as they moved into cultured cancer cells. In addition, toxicity studies showed that these fluorescent probes did not have a signficant effect on cell viability. This latter result is particularly important because quantum dots coated with PEI alone were highly toxic to cultured cells.
This work, which was funded in part by the National Cancer Institute's Alliance for Nanotechnology in Cancer, is detailed in the paper "Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings." Nie is the coprincipal investigator for the Emory-Georgia Tech Center. This paper was published online in advance of print publication. An abstract is available through PubMed.