Hybrid Gold-Dendrimer Nanoparticles Target and Image Tumors
Dendrimer nanoparticles, made of spherical, highly branched polymers, have shown promise as drug delivery vehicles capable of targeting tumors with large doses of anticancer drugs. Dendrimer nanoparticles have also been used to entrap metal nanoparticles, a combination that could serve as a potent imaging and thermal therapy agent for tumors if it were not for associated toxicity issues that researchers have had a difficult time overcoming.
To eliminate the toxicity associated with dendrimer-metal nanoparticle combinations, a team led by James Baker, Jr., M.D., principal investigator of a National Cancer Institute Cancer Nanotechnology Platform Partnership at the University of Michigan, has developed methods for modifying the surface of dendrimers laden with gold nanoparticles. This chemical treatment greatly reduces the toxicity of the hybrid nanoparticle without changing its size. Baker and his collaborators published the results of this work in the journal Small.
Of equal importance, the investigators also found that the chemical modification they developed makes it possible to add targeting molecules to the surface of the dendrimer. In the current work, the researchers added between four and five folic acid molecules to the surface of the dendrimer. Folic acid binds to a high-affinity receptor found on many types of tumor cells. Previous work by Baker's group and other teams has shown that nanoparticles coated with folic acid do target tumors and preferentially deliver their drug or imaging payloads to cancer cells.
After preparing the folic acid conjugated dendrimers loaded with gold nanoparticles, the investigators first showed that this construct was stable across a range of pH values and that the nanoparticles did not clump together under physiological conditions. Next, the investigators added these nanoparticles to tumor cells bearing the high-affinity folic acid receptor and found that the gold-laden nanoparticles accumulated within the cells. Microscopy studies showed that the nanoparticles massed within intracellular lysosomes. The researchers note that they are now repeating these experiments using animal models of human cancer.
This work, which was supported by the National Cancer Institute's Alliance for Nanotechnology in Cancer, is detailed in the paper "Dendrimer-entrapped gold nanoparticles as a platform for cancer-cell targeting and imaging." This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.