Joined: 03 Oct 2005
|Posted: Thu Oct 20, 2005 1:16 pm Post subject: Nanotech Method to Keep Methotrexate Inside Tumour Cells
|US Medical Researchers Use Nanotechnology Method to Keep Methotrexate Inside Tumour Cells
Methotrexate is a well-established anticancer drug, but many malignant cells develop a means of pumping this drug out of themselves almost as soon as the drug gets in the cell. Now, researchers at the University of Washington have used nanotechnology to keep methotrexate in tumor cells, while at the same time providing the means of following methotrexate as it is processed by the body.
Writing in the journal Langmuir, Miqin Zhang, Ph.D., and her colleagues at the University of Washington in Seattle describe the chemical techniques they use to attach just over 400 molecules of methotrexate to each 10-nanometer diameter iron oxide nanoparticle. Their method uses a linking molecule that will only release methotrexate from the nanoparticle when a specific enzyme, only found inside cells, is present. Indeed, experiments with the methotrexate-loaded iron oxide nanoparticle found that the combination was stable under a variety of conditions, except for those that matched the acidic, enzyme-laden conditions inside a part of the cell known as the lysosome.
Using human cancer cells grown in culture, the investigators then showed that the methotrexate-coated nanoparticle could enter cells via a receptor that normally binds the vitamin folic acid. The chemical structures of methotrexate and folic acid are similar, so this was not a surprise. The methotrexate-nanoparticle combination ends up inside lysosomes, where the necessary enzyme breaks the linker and releases free methotrexate into the cell. This process was easily followed by tracking the magnetic iron oxide component.
As free methotrexate builds up inside the cell, the cell tries to degrade it, but in doing so produces toxic metabolites that end up killing the cell. The researchers also showed that cultured heart muscle cells, which lack the folic acid receptor, did not take up the methotrexate-laden nanoparticles and were not killed.
This work is detailed in a paper titled, “Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells.” An abstract is available through PubMed.
Source: NCI Alliance for Nanotechnology in Cancer.