July 17, 2006
Herceptin-Linked Nanoparticles for Targeted Cancer Therapy
Albumin nanoparticles have recently proven their mettle as anticancer agents with the 2005 approval of Abraxane™ to treat metastatic breast cancer. Now, researchers in Germany have developed and optimized a mild chemical process for linking tumor-targeting agents to the surface of albumin nanoparticles, a development that could increase their utility in treating cancer.
Writing in the journal Biomaterials, a research team headed by Klaus Langer, Ph.D., at the Johann Wolfgang Goethe-University, in Frankfurt, Germany, describes the methods it developed for attaching a tumor-targeting antibody to the surface of nanoparticles made of human serum albumin (HSA). For this study, the researchers chose to work with trastuzumab, better known as Herceptin™, which binds to the HER2 receptor found on tumors in approximately 30 percent of breast cancer patients.
The key to the success of this project, say the researchers, was the attachment chemistry they refined that minimized the tendency of antibodies to react chemically with one another after they are attached to nanoparticles. As proof of principle, the investigators stored the resulting antibody-labeled nanoparticles for six weeks and found that the particles remained stable with no change in the binding ability of the antibodies or the size of the nanoparticles. Tests with breast cancer cells growing in culture confirmed that the trastuzumab-linked nanoparticles bound specifically to those cells over-expressing the HER2 receptor.
The researchers also found that the HER2-positive cells rapidly engulfed the nanoparticles. This finding shows that antibody-labeled albumin nanoparticles should be able to transport drugs efficiently into tumor cells.
This work is detailed in a paper titled, “Trastuzumab-modified nanoparticles: optimisation of preparation and uptake in cancer cells.” This work was published online in advance of print publication. An abstract is available through PubMed.