Synthesis Of Hollow Mesoporous Silica Spheres By Utilizing An Amphiphilic Block Copolymer As Template

In the past decade, there has been an increased interest in mesoporous silica materials for use as carriers in controlled drug release systems, to meet the need for their potential biomedical applications. Mesoporous silica nanoparticles (MSNs) have a tailorable mesoporous structure, high specific surface area and large pore volume. Thus, MSNs-based drug delivery systems (DDSs) exhibited significant advantages over traditional drug nanocarriers.Meanwhile, hollow nanostructured materials compared with the solid particles have attracted more extensive attention because of their unique properties, such as low density, large surface area, and high guest-loading capacity. Moreover, it is generally accepted that hollow spheres with mesoporous shells exhibit more advantages in mass diffusion and transportation over conventional solid particles. Therefore, hollow mesoporous silica nanoparticles (HMSNs) would be the better choice which can serve as extremely small containers for applications in drug delivery.In this work, HMSNs were successfully prepared in a facile route using poly (styrene-b-acrylate acid)(PS-b-PAA) and cetyltrimethyl ammonium bromide (CTAB) as co-templates. The thesis includes four parts:Part Ⅰ:Well-defined block copolymers PS-b-PAA were synthesized by atom transfer radical polymerization (ATRP), and the structure was analysed by gel permeation chromatography (GPC) and Fourier transform infrared spectroscopy (FTIR). In addition, the morphology and size of assemblies formed by amphiphilic copolymers in selective solvents were characterized by field emission scanning electron microscope (FESEM) and dynamic laser light scattering (DLS). The results showed that the size of the assemblies increased with increasing molecular weight in some conditions, and the assemblies always exhibited a spherical morphology in water/tetrahydrofuran (THF) solvent.Part Ⅱ:The synthesis of mesoporous silica nanoparticles has been studied by using PS-b-PAA with different molecular weight and CTAB as co-template, and HMSNs have been synthesized successfully. The products were analysed by FESEM, TEM, XRD, N2adsorption-desorption analysis and DLS, the results showed that the thickness of the shell increased by changing the addition of PS-b-PAA or the silica source relatively, the pore size could be increased by changing the addition amount of small molecule surfactant CTAB.Part Ⅲ:the drug release of Doxorubicin hydrochloride (DOX) as an model drug in HMSNs with different thickness of the shell and different pore size were studied. The results show that the thicker the shell was, the more the drug released; the larger the pore size, the more the drug released. Moreover, DOX-loaded HMSNs (DMSNs) displayed effective drug loading and a pH-responsive drug release character.Part Ⅳ:Finally, the cytotoxicity, blood compatibility of the HMSNs and the inhibition effect on HeLa cells were studied. It was demonstrated that the particle size is one of the most important parameters for the mediation of the biocompatibility of HMSNs, and the pore size have the insignificant influence. In general, HMSNs have good biocompatibility that can be used in DDS. It was also demonstrated that DMSNs have the similar cytotoxicity compared to free DOX, resulting in more inhibition of cancer cells.