Delivery of MTH1 inhibitor (TH287) and MDR1 siRNA via hyaluronic acid-based mesoporous silica nanoparticles for oral cancers treatment.

Oral cancer accounts for 95% of all maxillofacial malignant neoplasm. Presently, surgery and radiation (with and without chemotherapy) are the major treatments for oral cancer; however it met with limited therapeutic outcome. Overcoming the multidrug resistance and finding new therapeutic agents for oral cancer treatment are some of the serious challenges. Small molecule, TH287 potently and selectively inhibits the MTH1 protein in cells and could act as a new chemotherapeutic agent. The study reports the successful loading and delivery of MTH1 inhibitor - TH287 and MDR1 siRNA in oral squamous cell carcinoma. Our results showed that HA-assembled mesoporous silica nanoparticles were effective in controlling the drug release and internalization in CAL27 cancer cells. Cytotoxicity and apoptosis assay showed that combination of TH287 + MDR1 siRNA was significantly more effective in inducing the anticancer effect compared to that of TH287 (MTH1 inhibitor) alone. SiTMSN and HA-siTMSN significantly reduced the tumor burden compared to that of untreated control and free TH287. The study strongly supports the fact that the HA-siTMSN plays dual of inhibiting the MDR1 function and enhancing the cell killing effect of TH287 in the cancer tissues. Overall, results suggest that the HA-siTMSN platform is a promising vector the systemic delivery of MDR1 siRNA/TH287 and combinational therapeutics could be a viable solution for treatment of cancer of oral cavity.