Enhanced killing of colon cancer cells by mesoporous silica nanoparticles loaded with ellagic acid

Abstract: Natural compounds, including ellagic acid (ELG), have potentially a great antitumor efficacy with low adverse effects. However, their efficacy needs to be improved Nanotechnology permits to create nanoparticles as natural drug carriers and improve their in cancer therapy. We report an inorganic-organic nanostructure composed of mesoporous silica nanoparticles (MSN) functionalized with triptycene (TRP) and loaded with ELG, further called MSN-TRP-ELG nanoformulation. The nanoformulation contained over 11 wt.% TRP and approximately 25 wt.% ELG. It was tested for anticancer effects against two colon cancer cells: HCT-116 and HT-29 for treatment with up to 200 µM. Comparing to free ELG, we have shown a 3 times higher cancer inhibition. The lowest IC50 values were for HCT-116 (88.1±0.1 µM) and HT-29 (77.6±0.1 µM). When treated with free ELG the values were 187.1±0.10µM, and 300.0±0.07 µM, respectively. MSN-TRP-ELG enhanced cell death apoptosis primally via activating caspase-3, p53 and Bax. It also inhibited receptor tyrosine kinases (HER2 and VEGFR2) and upregulated Bcl-2 in HCT-116 and HT-29 cells. An important finding was that B-RAF CRAF and K-RAS were inhibited. The expression of B-RAF, C-RAF, and K-RAS oncogenes was also highly inhibited by the nanoformulation compared to free ELG. This research confirms the potential of nanomedicine for enhancing the efficiency in application of natural prodrugs, and in. particular ELG in cancer therapy and opens the way for further preclinical research.