Students: Amrinder Singh, Shervin Bayatmakou, Sobhveer Sandhu, Jack Coleman

Abstract: Cancer is one of the most aggressive diseases that can require the use of radical treatments such as chemotherapy and radiation treatment; undergoing either of these treatments can have severely debilitating effects on a patient. Radiation is a more localized treatment and generally has cytotoxic effects only within the patient’s area of exposure, while chemotherapy has cytotoxic effects on the entire body due to being administered intravenously or orally. Due to the universal effect of chemotherapy on the body, researchers have looked to develop and improve drugs to have less adverse side effects; a result of this endeavor is the drug Abraxane. Abraxane is an anti-cancer drug formed by dissolving Paclitaxel in albumin nanoparticles. The mechanism by which paclitaxel kills cells is by stabilizing microtubules during metaphase which prevents the progression of the cell cycle. Paclitaxel is effective on its own for cancer treatment but when paired with a delivery agent, i.e. albumin particles, the efficacy of paclitaxel is greatly increased. This is due to the albumin improving the bioavailability of paclitaxel to cells, allowing for more of the drug to diffuse through the membrane and reach effective concentrations within the cells. Prior to Abraxane’s development, the traditional delivery agent for paclitaxel was a compound called Cremophor EL, which had severe cytotoxic effects on both healthy and cancer cells alike. The creation of Abraxane demonstrated that through the use of carrier agents the bioavailability of paclitaxel could be greatly improved and the cytotoxic effects on healthy cells could be greatly reduced. While there is substantial literature on Abraxane and its effect on cells, there is less literature on treating cancer cells with paclitaxel paired with other carriers. Another agent that could increase bioavailability of paclitaxel as albumin does in Abraxane is a water soluble natural polymer[ . There is research on using water soluble polymers, such as starch, to create nanoparticles of paclitaxel but no data on the use of them in practical cancer treatment. Our proposal aims to study the pairing of paclitaxel with MR-007 bought from Nano Biotech to determine if it will improve the efficacy and safety of paclitaxel use in breast cancer treatment to a greater extent than Abraxane. This will first be determined in vitro by exposing human breast cancer cells to either Abraxane or the MR-007 reformulation and using the MTT assay to determine the cancer cell mortality of both experimental groups. Following this, in vivo testing will be performed on a rat model of breast cancer and analysis of cytotoxicity will be performed with a T-cell cytotoxicity assay.

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