SEATTLE – In recent years, researchers have developed nanoparticles for a host of medical applications, from drug delivery to imaging of tumors. Now, in a Nature Nanotechnology
paper published online July 26, 2009, a team at the University of Washington has reported a nanostructure that combines two such particles in a single package: a sort of Swiss army knife for nanomedicine.
“Each type of nanostructure has its strengths and weaknesses in biomedical imaging and therapeutics,” said Xiaohu Gao, lead author of the paper (Yongdong Jin is the other author) and a UW assistant professor of bioengineering. “By creating discrete and compact hybrid nanoparticles, one can take advantage of the strengths of each.”
Researchers have reported a nanoparticle that combines quantum dots and gold nanoshells, allowing different applications with the same structure. Previous attempts to combine these in a single nanoparticle have encountered obstacles because the gold tends to quench the quantum dots’ fluorescence. The investigators addressed this issue by creating a gap between the quantum dot core and the gold nanoshell and precisely controlling the distance between the two. They achieved this using a polymer – polyethylene glycol – increasing the distance by adding links to the polymer chain.
The “all in one” nanoparticle described in the paper combines quantum dots and gold nanoshells. The quantum dots can be used for fluorescence-based imaging, Gao said, and the gold nanoshells, for scattering-based imaging, hyperthermia-based therapy and simple bioconjugation. In addition, the thin gold shell could help to improve the quantum dots’ biocompatibility and in vivo stability.A difficult proposition
Other groups have sought to incorporate quantum dots and gold nanoshells in single particles, but maintaining the unique optical and electrical properties of each of these components has proved difficult. For example, when the two components are touching, the gold can completely quench the quantum dots’ fluorescence.
The researchers addressed this problem by creating a gap between the quantum dot core and the gold nanoshell. “By precisely controlling the separation distance, we could minimize the interference and preserve the unique properties from both semiconductor quantum dots and gold,” Gao said.
They achieved this by using a polymer, polyethylene glycol. The distance between the quantum dot core and the gold nanoshell was determined by the length of the polymer chain, and they could increase the distance with nanometer precision by adding links to the chain.
In addition, for successful integration of the two types of nanostructures, the gold nanoshell must be very thin. Conventional technologies used to grow gold nanoshells always use gold nanoparticles as seeds. Unfortunately, Gao said, because the gold nanoparticles are usually relatively large, the nanoshells prepared are often very thick, thus preventing light transmission from the core. To address this, the UW researchers used a trick from biology: the peptide polyhistidine (his-tag), which is widely used for protein purification because of its strong affinity to metal ions. They coated the outer surfaces of the quantum dots with a layer of polyhistidine, which effectively captured gold ions. Subsequent addition of reducing agents led to the formation of thin gold shells around the peptide.
They currently are working to fine-tune the distance between the quantum dot core and the gold nanoshell, seeking to produce much brighter quantum dots. “In theory, if the core-shell separation and spectral bands are optimized, the quantum dot fluorescence can be enhanced by several times,” Gao said.
In addition, they are testing the “all in one” nanoparticle for molecular sensing, imaging and therapeutic applications.