Delivery of dichloroacetic acid to colorectal carcinoma cells using non-toxic metal-organic frameworks

Abstract

Cancer is one of the leading causes of death worldwide, and our battle with it is ongoing due to the sheer number of documented cancers and the difficulty of treating them as a whole. Dichloroacetic acid (DCA) has been found to have anticancer properties along with its use for the treatment of lactic acidosis and diabetes. However, the clinical use of DCA is still under investigation due to its side effects and the fact that it breaks down too quickly in a biological environment before it can have an effect on the cancerous cells. Drug delivery systems, such as metal-organic frameworks (MOFs), are a promising approach to eliminating the limiting factors of administering free DCA. MOFs can be synthesized from a variety of metals and organic linkers, making it so that their properties can be designed to fit the need. This research attempted water-based synthesis methods to produce zirconium- and cerium-based MOFs, specifically Ce-UiO-66-Asp, Ce-UiO-66-Fum, MOF-801, and MIP-202, loaded with DCA. After characterization and analysis methods, it was determined that MOF-801 (zirconium-fumarate) had been successfully loaded with a very small percentage of DCA. The cytotoxicity of the MOFs not loaded with DCA was tested on HCT116 colorectal carcinoma cells as this cell line has not yet been explored with these MOFs before. This research found that analysis methods using NMR and an NaOH/D2O digestion scheme was insufficient in determining if DCA was present in the MOFs; however, IR spectroscopy did show DCA-loading in MOF-801. The water-based synthesis method was successful in producing MOFs, but the reaction time and temperature needs to be adjusted in future experiments. This research provided promising results that can further propel the outlook of utilizing MOFs as drug delivery systems in the fight against cancer.