Nanomaterials and Block Copolymers for Overcoming Multidrug Resistance in Cancer

The development of multidrug resistance in cancer is one of the leading causes for decreased chemotherapy efficacy and is particularly threatening to aggressive cancers such as that of the pancreas. In cancers where chemotherapy is amongst the few treatment options, it is crucial to develop chemotherapeutics that either bypass or control the development of multidrug resistance. Polymeric nanomaterials such as PluronicsRTM are of current interest due to their ability to perform these functions in addition to enhancing pro-apoptotic mechanisms. Using the respectively known chemosensitive and chemoresistant pancreatic adenocarcinoma cell lines MiaPaCa-2 and PANC-1, an in vitro analysis of the synergistic effect using 5-fluorouracil in conjugation with PluronicRTM F127 was performed. By monitoring cell viability and regulation of cell cycle, we were able to show that compared to the use of 5-flurouracil alone, there was enhanced cytotoxicity when using drug associated with PluronicRTM F127 in MiaPaCa-2 cells. The more chemoresistant cell line PANC-1 showed no significant enhancement of 5-fluorouracil cytotoxicity when associated with PluronicRTM F127. Enhanced cytotoxicity due to the use of PluronicRTM F127 may potentially become an exploitable feature for novel chemotherapeutic development in the future.