July 31, 2006
Intracellular Tracking with Coated Gold Nanoparticles
Gold nanoparticles, with their novel optical and physical properties, have rapidly become a favorite tool of biomedical researchers, yet their ultimate utility in cancer research and clinical oncology depends on an ability to stably link them to targeting molecules and drugs. A new “bifunctional” coating that firmly attaches to the surface of gold nanoparticles while also providing an anchoring point for proteins and other molecules could overcome that limitation.
Mansoor Amiji, Ph.D., and colleagues at the Northeastern University Cancer Nanotechnology Platform Partnership have created a modified form of the biocompatible polymer poly(ethylene glycol) (PEG) to act as an all-purpose linker between gold nanoparticles and other molecules. In its native form, PEG has alcohol groups at each of its ends, and the Northeastern team had to solve the problem of converting only one of those alcohol groups into a thiol group, essentially swapping an oxygen atom for a sulfur atom. Sulfur forms tight chemical bonds with gold, while the remaining free alcohol group can create a chemical link to a wide variety of molecules.
The PEG molecule also acts as a spacer, affording enough distance between the gold nanoparticle and an attached protein, for example, so as to not interfere with the interaction of that protein with its biological target. In addition, PEG renders the particles invisible to macrophages, immune system cells that normally scavenge particles in the bloodstream, and prevents the gold nanoparticles from clumping in the bloodstream.
Having found a solution to this problem, the investigators used their bifunctional PEG to link a model fluorescent dye molecule to gold nanoparticles. They conducted toxicity assays with the resulting particles, finding that this construct was not toxic over a wide range of doses. The researchers then followed the nanoparticles, using fluorescence microscopy, as cells ferried the nanoparticles across their outer membranes and as the particles traveled within the cells. The researchers noted that the ability to attach a wide variety of molecules to the surfaces of gold nanoparticles and image them as they move through the cell should provide new tools for studying intracellular transport mechanisms.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery.” This paper is available free of charge through PubMed Central.