Holmium Periodic Mesoporous Organosilicas for Concurrent Chemotherapy and Radiotherapy

The goal of this project was to combine chemotherapy and radiation therapy by utilizing novel wrinkle structured periodic mesoporous organosilica (PMO) nanoparticles for concurrent treatment. Combining the two treatments is highly beneficial because chemotherapeutic drugs often act as radiosensitizers, making cancer tumors more sensitive to radiotherapy while leaving normal tissue unharmed. Lower amounts of radiation can be given while increasing damage to cancer cells, ultimately improving patient survival rate. For concurrent treatment, PMOs act as a suitable vehicle to contain both parts of treatment. Periodic mesoporous organosilicas (PMOs) are mesoporous silica based materials that incorporate both organic and inorganic groups into their pore walls, allowing compatibility with many hydrophobic drugs. Benefits of such a structure include high chemical and thermal stability and biocompatibility. Furthermore, the novel wrinkle pore structure enhances surface area and maximizes loading capabilities. The organic benzene ring in the PMO structure also allows for functionalization, such as sulfonation, that can bind metal cations like holmium (III). The functional groups bind to holmium ions, which are then neutron activated to generate beta and gamma radiation therapy and provide imaging and tracking, while chemotherapeutic drugs are loaded into the pores, offering concurrent treatment. By incorporating both approaches in the same particle, delivery to the same location is ensured.  In conclusion, this research successfully synthesized novel holmium wrinkle structured PMOs through sulfonation to provide simultaneous internal chemotherapy and radiation therapy. Characterization demonstrated the properly formed PMO spheres and wrinkle structure, with a diameter of 100 nm, suitable for drug delivery. The increased surface area from the novel wrinkle structure was also quantified using BET analysis. Furthermore, Raman spectroscopy and EDX images demonstrated successful functionalization and chelation of holmium. Drug release was studied under in vitro and the data shows that the PMOs released the loaded hydrophobic anti-cancer drug, paclitaxel. By using this wrinkle structured PMO, holmium and paclitaxel can be combined to provide concurrent radiation therapy and chemotherapy, offering cancer patients an alternative, more effective treatment.