Synthesis of self-assembled nanoporous silica for therapeutic delivery

Abstract

In the recent years, nanoporous silica materials have been regarded as promising nanocarriers to deliver various therapeutic agents, due to their high pore volume and surface area, ease of surface functionalization and excellent biocompatibility. Although numerous porous silica nanoparticles have been developed for therapeutic delivery, more efforts are still needed in the synthesis of nanoporous silica nanoparticles simultaneously possessing good dispersity, high uniformity, small particle size (< 200 nm) for efficient cellular uptake and sufficient pore size to encapsulate desired therapeutic agents with large molecular sizes. This thesis focuses on synthesizing self assembled porous silica nanoparticles for high performance of biomedical applications. Three types of porous silica nanoparticles, including silica vesicles, SBA-15 rods and mesoporous organosilica nanoparticles will be synthesized. The self assembly based formation mechanism will be discussed, which is believed as a key to design porous silica nanoparticles with superior and more controllable structures and properties. In addition, their drug/protein loading capacity and release profile, biocompatibility, cellular uptake performance, and therapeutic efficacy will be evaluated in vitro.The first part of the experimental chapters focuses on the synthesis of silica vesicles (SVs) with a diameter of 30 nm and reduced aggregation using mixed triblock copolymer surfactants as the structure-directing agents, tetraethyl orthosilicate (TEOS) and tetrapropyl orthosilicate (TPOS) as mixed silica sources. The reduced aggregation is attributed to the incompletely hydrolysed hydrophobic -OCH 2 CH 2 CH 3 groups of TPOS on the surface of SVs, thus preventing the inter-particle aggregation. The drug delivery performance of SVs is evaluated using a photosensitizer ─ silicon phthalocyanine The cellular uptake of SR-3.40, SR-3.88 and MCM-41 in human osteosarcoma cancer cells is visualized using confocal image and quantified using ICP technique, revealing the significantly enhance cellular uptake efficiency of SR-3.88 (7.4 pg/cell) compared to SR-3.40 (2.0 pg/cell) and MCM-41 (6.1 pg/cell). Hence, the SBA-15 rods with small particle sizes, large pores as well as excellent biocompatibility are believed as a promising delivery system for cellular delivery of large molecular weight therapeutic agents with improved efficacy.Lastly, we tuned the composition of porous silica nanoparticles by incorporating benzene groups in the silica framework to synthesize large pore well dispersed mesoporous organosilica nanoparticles (MOSNs) by using a biphase synthesis approach. The role of the biphase system has been demonstrated essential to enlarge pore size and facilitate the surfanctant/organosilica precursor assembly. The obtained MOSNs with pore size of 7.6 nm show enhanced protein loading capacity at 144.5 μg mg -1 and sustained release profile over 72 hours. In order to investigate the potential in biomedical application, the efficient cell uptake is firstly visualized...

The Impact of Mesoporous Silica Nanoparticles on Electrochemical Performance

“…In this study, mesoporous silica nanoparticles were synthesized using Stöber method [14]. Noctadecyl trithoxysilane (C18TMS) was used as an aqueous surfactant and as a directing agent in the synthesis of mesoporous silica [15]. The surfactant directs the polymerization of silicates from a precursor, typically an ester of orthosilicic acid.…”