US researchers have recently developed tiny artificial “nanobees”, which are armed with a cancer-killing toxin found in bee venom, that literally sting tumors to death. Tested on mice, after four to five injections of the Melittin-carrying nanobees over several days, the growth of breast cancer tumors in the mice was slowed by nearly 25 percent. Melanoma (skin cancer) tumors shrunk in size by 88 percent. Saudi Gazette asked Debabrata Mukhopadhyay, Ph.D., a Professor at the Nanotechnology Laboratory at Mayo Clinic, Minnesota - via an email interview - the scope and implications of this research. “The main propose of this work is to deliver toxic drugs into the tumors in a targeted manner and side by side to overcome drug resistance of the tumor cells. In this regard, the authors made use of Melittin, a water-soluble peptide derived from the venom of the honeybee and formed a nanoemulsion-peptide complex. Melittin is highly toxic to the cells and disrupts the cellular membrane, killing the cells. If the cancer cells come closer to the Melittin, its membrane will be broken down; therefore the traditional mechanisms of cancer resistance cannot happen,” explained Mukhopadhyay. “The uniqueness of the paper,” he continued, “is that the authors developed the nanoemulsion and put a tumor targeting agent that helps to deliver this highly toxic drug straight to the tumor mass and bypass the toxic effect of the venom. Therefore, the authors claimed that this nanoemulsion-peptide could kill the cancer cells precisely without damaging normal cells.” Commenting on the potential risks involved in this cancer treatment, he said: “Considering the lipid-based nanoemulsion, it can be very specific. Nonetheless, without proper clinical trials it will be difficult to assess. A couple of important aspects can be considered in treatments: bone marrow toxicity, liver toxicity, and anemia. Again, unless these drugs can be tested in bigger animals (such as dogs) with more immune-competent systems, the risks involved will be difficult to say.” The use of nanobees in cancer treatment is still in the experimental stage, and Mukhopadhyay said he sees it as a potential commercially viable treatment. “But, before going to the clinical stage, these nano-conjugates must pass through several pre-clinical testings. More angiogenesis-driven tumors could be brought into the loop as well,” he said. The research also brings into focus the powerful bee toxin – Melittin - and its use in disease treatment. “In several parts of Asia, such as, China and Korea, Bee Venom therapy (BVT) has been used for several diseases such as multiple sclerosis to relieve the symptoms associated with disease. Melittin is a powerful anti-inflammatory substance as well and may be 100 times more potent than hydrocortisone. Melittin also helps to activate the body's adrenal glands, which stimulate one's own natural healing response. However, more research is required to understand the basic biology of this peptide,” said Mukhopadhyay. The “nanobee” research was conducted by Professor Samuel Wickline and Dr. Paul Schlesinger, from the Siteman Center of Cancer Nanotechnology Excellence at Washington University School of Medicine, and reported last month in the Journal of Clinical Investigation. It said the flexibility of the nanoparticles meant they could readily be adapted to fit different medical situations as they arise. ““Flexibility” here means that it is not difficult to alter the nanoparticles by attaching different targeting agents or composition. That means if we would like to deliver a particular cancer then we should use one targeting agent whereas other cancers may need a different targeting agent. Therefore, depending upon the need, the nano-fabrication can be modified; so there is flexibility,” explained Mukhopadhyay. The report also stated that Melittin, when injected directly into the bloodstream, can cause widespread destruction of red blood cells. “There are hundreds of people stung by bees that only have temporary pain; however, with higher doses that can be dangerous just as multiple bee stings can kill large animals as well as people. Also, there are many people who are allergic to bee stings where even one bee sting can be lethal. Due to this, more careful evaluation is necessary prior to using this substance.” he added. The use of nanotechnology in biology has grown over recent years, incorporating the use of reagents such as gold nanoparticles to directly deliver bioconjugates. Mukhopadhyay and his team are examining the use of gold nanoparticles and other bioconjugates as messengers to deliver reagents that are capable of manipulating the angiogenic response (formation of new capillaries) in vivo. “We are working on a similar approach to target tumors and their microenvironment by using gold nanoparticles as a drug delivery vehicle. We have successfully delivered the conventional drugs mainly to the tumor cells in a targeted manner and also can monitor the therapeutic outcomes. These studies have been carried out primarily in the preclinical environment. There are several approaches we are currently working on to determine a proper use for nano-medicine to treat the cancer patients where no surgery is possible,” he said, hoping that within a two to three year timeline, the strategy can be delivered to the clinic with proper support from the government or private donors. Caution, he said, is the keyword before the treatment is applied in clinics. “The National Institutes of Health predicted several years ago that nanotechnology will change our current way of diagnosis, treatment, and prevention of diseases. We are close to that prediction, but it's not been executed yet. We would like to be very cautious and need to know more about nanoparticle behaviors in biology; and this should be a parallel process.” Mukhopadhyay concluded that the use of nano-medicine is nothing new. “If you look at ancient Indian or Chinese medicine, the use of metal-based nanoparticles (including gold) began several thousand years ago. However, the problem is the quality control of the drugs. Again, we should be more cautious and methodical before we apply these medicines in clinics. Therefore, multi-disciplinary teams, such as basic scientists, clinicians, physicists, chemists and others need to be involved to develop safer, efficient, and affordable drugs for the next generation,” he said.
