Enhanced anticancer drug delivery using electrical pulses.

摘要

Many drugs that have the potential to treat cancers have had limited success due to their lack of efficient and safe delivery mechanisms that allow the drug molecules to cross cell membranes. Electrical pulses-mediated drug delivery, known as electroporation, is gaining attention as a possible approach to enhance uptake of chemotherapy. It delivers anticancer drugs with enhanced efficacy and fewer adverse effects. It is a physical (thus, applicable to all types of tumors) and is minimally invasive.;In this thesis, research is focused on investigating the efficacy of electroporation-based drug delivery to breast cancer cells. For this purpose, three different, most commonly used, and FDA approved anticancer drugs, Paclitaxel, Bleomycin, and Tamoxifen, were chosen to investigate their efficacy for different electrical pulse parameters. MCF-7 human breast cancer cells were used for this purpose. The results obtained using various biological assays, such as viability, Fluorescence Activated Cell Sorting (FACS) analysis, Fluorescence Microscopy and Impedance Spectroscopy indicate that the combined therapy using electrical pulses and chemodrug is more effective than drug alone. In addition, electric field simulation using MATLAB was studied as it influences pore formation. The results showed the strong impact of electric field on cell viability via its influence to the pore distribution in the cell membrane.;For the first time, the effect of electroporation parameters on breast cancer cells has been explored in this project. Our results demonstrate that application of electrical pulses with chemotherapy may benefit patients by enhancing the drug transport across the plasma and could be transferred to clinical practice, especially to those who are not responsive to conventional chemotherapy.