For most people, bees bring to mind one of two things: delicious honey or nasty stings. If someone were to tell you that a bee product was being used medicinally you might be inclined to think that it was a spoonful of honey for a sore throat or something equally benign. Recently, however, scientists have been studying the curative properties of bee venom, particularly the compound melittin, its active ingredient. This compound, which is responsible for much of the pain and cell death caused by bee stings, has been combined with nanotechnology in a recent study to form “nanobees,” which Nanobees could present a possible alternative to current chemotherapy for cancer.
As early as the late 90s, scientists had thought about synthesized melittin as a possibility in cancer treatment to avoid the drawbacks of regular chemotherapy, most notably nonspecificity. Melittin itself is a host-defense peptide, a category known to have anti-cancer properties. The advantage of a synthesized version of melittin is that it would eliminate the allergenic elements of the bee venom and that there would be no need to use actual bees to extract the compound. Melittin is also preferable to other anti-tumor compounds as it targets and causes lysis of cell membranes, so it is difficult for the tumor cells to build immunity against it. The original plan was to create an immunotoxin, a combination of the synthesized melittin and an antibody that could detect the cancer cells. This year the delivery of this synthesized version was finally realized through the use of nanotechnology.
Despite the availability of a synthesized version of melittin, delivery of large quantities remained difficult. Melittin is highly toxic, and the doses desired to affect largescale tumor cell death would easily kill healthy cells as well. Nevertheless, Dr. Samuel Wickline and his team from the Siteman center of Cancer Nanotechnology Excellence at Washington University in St. Louis, discovered a material that could easily adhere to melittin and protect the body from its effects until its delivery. The nanoparticles that eventually became “nanobees” are tiny spheres made from a mixture of “an oily substance known as perfluorocarbon, fatty substances called lipids, and lecithin, which is found in egg yolks.” The nanoparticles allowed the mice in the experiment to receive one hundred trillion nanobees per dose, an amount of melittin that would have killed them without the coatings by causing massive death of their red blood cells.
In addition to allowing large amounts of drugs to be delivered, the nanobees also protect the melittin itself from the body’s defense system, allowing it to circulate and giving it more time to locate tumors. The finishing touch was a ligand that helps the nanobees locate tumors by a chemical affinity for a protein common in the new blood vessels that tumors form to feed themselves. In the test mice this led to a decrease in both tumors and precancerous lesions: a 25% decrease in tumor size for those with breast cancer over a week and 88% decrease in those with melanoma. This is particularly promising as these are considered to be different categories of cancer. The scientists hope that this treatment will go into clinical trials and be available to people soon.
Now that this technique has been successful in mice, scientists are looking into many new uses for both melittin and nanotechnology in medicine. Nanoparticles are being used to encapsulate already approved cancer drugs, as in one study with docetaxel, a prostate cancer drug, which uses the nanoparticle to deliver the drug directly to the tumor rather than having it circulate in the body and potentially harm other cells. Another related one is to attach an imaging particle to a deactivated nanobee to visually track drug delivery and tumor response. Who would have thought that a bee’s venom would have more healing properties than its honey?
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2. Peter Loftus, “Targeting Tumors with Bee Venom,” The Wall Street Journal, September 28, 2009, http://online.wsj.com/article/SB10001424052970203803904574433382922095534.html.
3. CSIRO Australia, Science Daily.
5. “´Nanobees´Destroy Cancer Cells by Delivering Synthesized Bee Venom to Tumors” CNN, August 19, 2009, http://www2.counton2.com/cbd/news/science/article/nanobees_destroy_cancer_cell_by_delivering_synthesized_bee_venom_to_tumors/55578/.
6. Peter Loftus, The Wall Street Journal.
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10. Neelesh R. Soman, Steven L. Baldwin, Grace Hu, Jon N. Marsh, Gregory M. Lanza, John E. Heuser, Jeffrey M. Arbeit, Samuel A. Wickline, Paul H. Schlesinger, “Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth”J. Clin. Invest. 2009; 119(9):2830, http://www.jci.org/articles/view/38842.
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