By Brook Teffera
The American Cancer Society estimates that 1600 Americans will die every day in 2013 due to cancer, a condition characterized by the unregulated growth of cells. Only 5% of all cancers can be linked to heritable causes; the other 95% is caused by gene degradation over one’s lifetime. The five year survival rate of individuals living with cancer has significantly improved over the years, from a 49% survival rate from 1975-77 to 68% survival rate from 2002-08, indicating the medical advancements made over the year. These advancements include prevention, more localized surgical methods, and chemotherapy, which use powerful chemicals to purge the body of any mutated cells.
Although there has been improvement in the treatment of cancer patients, there is still a long way to go. Chemotherapy in particular is infamous for its side effects, which include nausea, balding, and diarrhea. It employs chemicals that are structurally similar to mustard gas, a lethal chemical used in World War I. Most of these drugs follow a bimolecular and concerted mechanism, attacking cells during mitosis at the progression from metaphase to anaphase and inhibiting cell division. However, the drugs are not delivered specifically to cancerous cells, leading to the destruction of healthy and unhealthy cells indiscriminately.
Bill Zamboni, associate professor at the UNC Eshelman School of Pharmacy, focuses on utilizing nanoparticles that discriminate between healthy and cancerous cells in order to reduce the extent of the adverse side effects associated with chemotherapy. These particles can attack tumor cells via passive or active targeting. The former puts the therapeutic nanoparticles into the blood stream with the hope that the chemicals enter the tumor through some opening or perforation. The latter involves the binding of nanoparticles to surface receptors on the tumor cells. The figure below shows the effect that this treatment option has on mouse models of prostate cancer. Red shows conventional use of the chemotherapeutic docetaxel, passively targeted nanoparticles transferring docetaxel are measured in green, and actively targeted nanoparticles transferring docetaxel are in blue. Tumor growth without treatment is presented in purple.
As indicated by the figure, nanoparticle transferred chemotherapy is very effective at treating cancer, with active targeting being the most effective. However, this treatment option has some obstacles that need to be addressed before nanotechnology becomes the norm in fighting cancer. Firstly, there is the necessity of maintaining the sterility of the drug; most will be delivered intravenously, and using heat for sterilization will denature a majority of the nanoparticles and render them useless. Sterilization via gamma radiation leads to the same predicament. Also, the release rate of the drugs being transported by the nanoparticles must be controlled, otherwise the efficiency and safety of the treatment option will rapidly decline. In addition, the contamination of the drugs transported by nanoparticles is a risk that is compounded by the fact that it is difficult to remove such drugs from the system.
Dr. Zamboni’s current research has provided insight into this last impediment. His study uses a probe that can determine the strength of the mononuclear phagocyte system (MPS) in individuals. This system is involved in the removal of nanoparticles from the body and is an indicator of the dosage needed for a specific patient. According to Dr. Zamboni, “the more active the MPS system, the faster these drugs are cleared from the patient”. This realization creates the opportunity to predict the removal of any contaminated chemotherapeutics applied through nanotechnology. Although these nanoparticles may be too small to notice, it is clear that significant strides in oncology are on the horizon for this treatment option.