Enhanced Killing of Colon Cancer Cells by Mesoporous Silica Nanoparticles Loaded with Ellagic Acid.

[BACKGROUND] Natural compounds, including ellagic acid (ELG), are promising anticancer agents with low adverse effects. In this paper, we test in vitro the effectiveness of mesoporous silica nanoparticles (MSN) as an ELG carrier against colon cancer.

[METHODS] We produced MSNs functionalized with triptycene (TRP) and loaded with ELG, further called MSNTRPELG nanoformulation. The nanoformulation contained over 11 wt.% TRP and approximately 25 wt.% ELG in the mesoporous structure and on the surface of particles. It was assessed for anticancer effects against two colon cancer cells: HCT-116 and HT-29 for treatment with up to 200 µM.

[RESULTS] Comparing to free ELG, we have shown a three 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 ± 0.1 µM and 300.0 ± 0.1 µM, respectively. MSNTRPELG enhanced apoptosis primarily by activating caspase-3, p53, and Bax while downregulating Bcl-2 in HCT-116 and HT-29 cells. It also inhibited receptor tyrosine kinases (HER2 and VEGFR2). Preliminary Western blot observations suggest suppression of B-RAF, C-RAF, and K-RAS oncogenes, with stronger inhibition by the nanoformulation than by free ELG.

[CONCLUSIONS] This work highlights the potential of MSNs to enhance the efficacy of natural prodrugs, particularly ELG, in cancer therapy.