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Sci Tech
Molecular nanogenerator to destroy cancer cells
RESEARCHERS at Memorial Sloan-Kettering Cancer Center (MSKCC) have developed a molecular nanogenerator that releases a cascade of atomic fragments known as alpha particles on the inside of cancer cells. These nanogenerators consist of a single radioactive atom contained inside a molecular cage and attached to an antibody that homes in on cancer cells carrying the generator to the interior of those cells and destroying them.
The results of this work are published in the journal Science.``We have found an effective way of containing and then delivering this highly potent element directly into cancer cells,''said study senior author David A. Scheinberg, Chief of MSKCC's Leukemia Service and head of the Laboratory of Hematopoietic Cancer Immunochemistry at the Sloan-Kettering Institute.
The investigators tested the nanogenerators in cell culture in a variety of human cancer cell types: leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate.
They found the nanogenerators could kill all these types of cancer cells at extremely low concentrations. Scheinberg and colleagues also tested the treatment in two mouse models, one for prostate cancer and one for disseminated (widespread) lymphoma.
Many of the animals had long-term survival, and all of them had their lives extended after a single treatment at a low dose. In addition, many of the mice with prostate cancer had their prostate-specific antigen (PSA) levels decrease to zero and most others had PSA levels that were reduced. PSA levels are a common measure of the presence of prostate cancer in humans. The atom contained inside the nanogenerator is actinium-225.
Actinium decays by giving off short-lived, high-energy alpha particles that blast through cancer cells and destroy their DNA and proteins. When actinium decays, it produces a series of three daughter atoms each of which gives off its own alpha particle.
Each particle increases the chance that the cancer cell will be destroyed. Targeting the generator to the inside of the cancer cells also increases the treatment's effectiveness.
``If the atom is sitting on the outside of the cell, the alpha particle can travel in any direction, and it kills the cell only a fraction of the time,''explained Michael McDevitt, a senior research scientist.``If the generator is inside the cell, every particle will be effective.''
In addition, keeping the generator inside the cell greatly reduces the possibility that the daughter atoms could float off and damage healthy cells. A large part of this advance was the development of antibodies that target various types of tumour cells in humans.
In addition, researchers were able to identify an appropriate atom, actinium (which has long enough half-life to allow doctors time to administer the drug after it has been manufactured). Finally, the researchers found a molecular cage that would hold the actinium atom
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