May 8, 2006
Advancing Nanoparticle-Based Imaging
and Therapy of Brain Cancer
Brain cancer is one of the most difficult malignancies to detect and treat, in large part because of the difficulty in getting imaging and therapeutic agents past the so-called blood-brain barrier and into the brain. Several groups of investigators have found that nanoparticles hold promise for ferrying such agents into the brain (click here for more information), and now two new papers published in the Journal of Pharmacology and Experimental Therapeutics provide additional hope that nanotechnology may yield important advances in detecting and treating brain cancer.
In an attempt to breech the blood-brain barrier, Klaus Langer, Ph.D., and his colleagues at the Johann Wolfgang Goethe University in Frankfurt, Germany, attached apolipoprotein E (AopE), a protein that the body uses to transport cholesterol and fatty acids through the bloodstream and into the brain, to the surface of albumin nanoparticles. Albumin nanoparticles have already been used successfully to deliver the anticancer drug paclitaxel to breast tumors as part of the recently approved drug Abraxane® (click here for earlier news story).
Using a painkiller that cannot enter the brain as a model drug, the investigators showed that albumin nanoparticles decorated with chemically attached ApoE is able to transport large amounts of this drug across the blood-brain barrier in mice. To prepare these nanoparticles, the researchers first created albumin nanoparticles loaded with the model drug. They then used poly(ethylene glycol) and a second linker to anchor the ApoE molecules onto the surface of the nanoparticles. The resulting nanoparticles were then administered to mice via intravenous injection and were shown to exhibit the desired analgesic effect.
In the second paper, Lucienne Juillerat-Jeanneret, Ph.D., and her colleagues at the University Institute of Pathology in Lausanne, Switzerland, presented the results of a study designed to characterize how various coatings would affect the brain biocompatibility of iron oxide nanoparticles. Iron oxide nanoparticles have already shown promise in brain cancer imaging and therapeutic studies.
In this study, the investigators coated iron oxide nanoparticles with dextran or various types of polyvinylalcohols and then examined how these particles interacted with different types of brain cells and three-dimensional aggregates of brain cells. The investigators measured cell uptake and toxicity. While none of the coated nanoparticles were toxic to brain cells or triggered the release of molecules that would signal that an inflammatory response was occurring, the investigators did find that nanoparticles with one particular coating, known as amino-polyvinylalcohol, were taken up in much greater numbers. The investigators concluded that iron oxide nanoparticles coated with amino-polyvinylalcohol could prove to be biocompatible agents for imaging brain diseases, including cancer.
The work on enhanced brain delivery of nanoparticles is detailed in a paper titled, “Covalent linkage of apolipoprotein E to albumin-nanoparticles strongly enhances drug transport into the brain.” An investigator from the Albert Ludwigs University in Freiburg, Germany, also participated in this study. This work was published online in advance of print publication. An abstract of this paper and a link to the free full-text article is available through PubMed.
View abstract and link.
The work testing biocompatibility of coating iron oxide nanoparticles is detailed in a paper titled, “Interaction of functionalized superparamagnetic iron oxide nanoparticles with brain structures.” Investigators from McGill University in Montreal, Canada, and from the Swiss Federal Institutes of Technology in Lausanne also participated in this study. This work was also published online in advance of print publication. An abstract of this paper and a link to the free full-text article is available through PubMed.
View abstract and link.