NIST, NCL Endeavor to Create Made-to-Order Gold Nanoparticles

Researchers have great expectations for gold nanoparticles, which they hope will play a major role in drug-delivery systems, cancer therapy, and diagnostic imaging applications. Because gold is nontoxic and can be fashioned into particles in a range of sizes and shapes, it can be used as a vehicle for attaching protein-based drugs and molecules for targeting specific cancer cells.

To enhance the efficacy of gold nanoparticles in a range of future medical device applications, researchers from the National Institute of Standards and Technology (NIST; Gaithersburg, MD) and the National Cancer Institute's Nanotechnology Characterization Laboratory (NCL; Frederick, MD) are setting out to create a gold nanoparticle 'testbed' to explore how these tiny particles behave in biological systems. At the same time, they are attempting to establish a paradigm for how to characterize nanoparticle formulations to aid researchers in determining what they're working with.

For use in the body, gold nanoparticles are generally coated to prevent them from clumping together and being attacked by the body's immune system. In an effort to characterize gold nanoparticles, the NIST/NCL team is attempting to understand coating composition, density, and stability in order to ensure the safety, biocompatibility, and effectiveness of nanoparticle-based delivery systems. Their goal is to design and develop better nanomaterials, according to NCL's Anil Patri.

Pursuing this goal, the scientists have developed a nanoparticle testbed that consists of a uniform, controllable core-shell nanoparticle capable of being formed into a precise shape and size and capable of serving as a platform for nearly any clinical application. The researchers have also studied how controlled variations fare in a biological system.

Their trial coating system is based on regularly shaped branching molecules called dendrons. Unlike polymers, dendrons are always the same size and can be modified to carry payload molecules. At the same time, the tip of the dendron structure--its tree trunk, so to speak--is designed to bond easily to the surface of a gold nanoparticle.

The team made an exhaustive set of measurements so that they could thoroughly describe their custom-made dendron-coated nanoparticles. "There aren't a lot of protocols around for characterizing these materials--their physical and chemical properties, stability, et cetera," remarks NIST chemist Vince Hackley, "so, one of the things that came out of the project is a basic series of measurement protocols that we can apply to any kind of gold-based nanoparticle." Any single measurement technique, he says, is probably inadequate to describe a batch of nanoparticles, because it likely will be insensitive to some size ranges or confused by other factors--particularly if the particles are in a biological fluid.

A NIST/NCL paper on this subject begins to catalog analysis techniques for understanding nanoparticles, including nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry, dynamic light scattering, ultraviolet/visible spectroscopy, and x-ray photoelectron spectroscopy. The dendron-coated nanoparticles also were tested for stability under biologically relevant temperature and acidity conditions and were also tested for resistance to recognized forms of chemical attack that would take place in the bloodstream. In vitro biological tests are pending.