Mesoporous silica nanoparticles for biomedical application

Abstract

Ordered mesoporous silica materials disclosed over the past two decades have been extensively used in many applications as nanocarriers for delivering various therapeutic/ diagnostic agents, due to their ease of synthesis and surface functionalization, tunable pore size, and pore structure, high surface area, pore volume and controllable morphology. Currently, many research attempts have focused on the synthesis of mesoporous silica nanoparticles (MSN). Significant progress has been achieved to date. However, specific biomedical applications, for example, in the design of tablet formulations, as safe adjuvants in vaccine delivery and in combined cancer therapy should be developed further to explore the potential of this family of interesting materials.The aim of this project is to develop novel and facile approaches to prepare monodispersed MSN with finely controllable pore size and morphology for 1) to developing floating tablets, and 2) to gain insight into the role of particle morphology on hemocompatibility and adjuvanticity, and 3) to study the efficiency of combined therapy for cancer treatment. The main achievements obtained in this thesis are listed below.In the first part, novel floating tablets are designed using MSN for enhancing the drug delivery performance of both hydrophobic and hydrophilic drugs compared to conventional floating tablets. The drug released was tested from floating tablet, where the water soluble drug loaded MSN containing floating tablet show a sustained release than a conventional tablet. More importantly, dissolution improvement for the hydrophobic drug was achieved, an issue that was not solved with a conventional floating tablets.In the second part, asymmetric MSN with controllable head-tail structures were successfully synthesised. The tail length (~25-170 nm) and tail coverage on head particles are adjustable with varying the reaction time and tetraethyl orthosilicate (TEOS). Furthermore the head particle is tunable (solid silica to porous silica). The synthesised particles were tested for hemocompatibility. Furthermore, we applied the smooth solid silica spheres and head-tail MSN for uptake and activation efficiency in dendritic cells (DCs) and macrophages. Compared to solid head particles or MSN with fully covered, dendritic large pores, asymmetrical HTMSN show surprisingly higher hemocompatibility towards red blood cells. Further, HTMSN were analyzed for immunoadjuvant activity. Interestingly, we found that asymmetrical HTMSN exhibit a higher level of uptake and in vitro maturation of antigen presenting cells compared to spherical head particles.In the third part, multifunctional core-shell-structured dendritic mesoporous silica nanoparticles with a fullerene doped silica core and a dendritic silica shell with large pores have been successfully prepared. The designed dendritic silica spheres with fullerene core (FD) have a particle size of ~110 nm and pore size of ~25 nm, which can be easily modified with octadecyl group. The prepared FD with big pore size after hydrophobic modification (FD-C18) shown good loading efficiency of big antibody (anti-pAkt). The FD-C18 has high cell internalization compared to FD, which was confirmed by ICPOES test and confocal and, the particle are less toxicity to breast cancer cell line (MCF-7) up to 160 ug/mL. The FD-C18 showed significant cell inhibition of ~ 85 % in combined therapy, while pure antibody shown only negligible cytotoxicity in breast cancer cell line (MCF-7).