During the first 10 months, the synthesis method for producing MSNs with controlled size and composition (80-250 nm) was developed by modifying the sol-gel Stöber method. A reproducible method was developed and 80.24 ± 11.80 nm spherical MSNs with high surface area (725 m2/g) were used to incorporate therapeutic ions such as cerium, calcium, strontium, zinc and iron and to provide their sustained and controlled release. The process was followed by material characterization (composition, size, shape, amorphous nature and magnetic properties).
From the 8th to the 13th month work focused on the optimisation of the MSNs for cell studies and for understanding how cells take up the particles and what is likely to happen when they do so. Biodegradation and ion release was evaluated in physiological conditions (pH=7.4) and acidic conditions (pH=5.85) which mimicks the environment inside the cells.
From the 12th to 20th month the interaction of the NPs with cells, such as bone growing cells (osteoblasts, OBs) and bone remodeling cells (osteoclasts, OCs) was investigated, including toxicity and internalization (and fate) of the nanoparticles into the cells, which was monitored by TEM and by confocal microscopy on fluorescent labelled NPs. A dose-dependant effect of concentration of NPs on toxicity was identified.
The most promising ceria containing NPs were chosen to test their antioxidant capability in bone growing (MC3T3-E1) cells when the cells were treated with the oxidizing agent t-butyl hydroperoxide (TBHP). They reduced the number of ROS present. Co-cultures of OBs and OSC (RAW264.7) showed that OBs produced new bone matrix while the OSC activity decreased.
The last part of the project (from the 19th to 24th month) included design of the NP delivery system not only for osteoporosis treatment but also for neurodegenerative disease and cancer treatment. The MSNs were found to be a promising carrier for different kind of ions.
To enable technology transfer of the NPs, the Fellow is applying for Faculty positions at prestigious universitiess such as Imperial College London, University College London, King's College London. EPSRC Early Career and Imperial College Research Fellowships are in preparation.
