Synthesis of Silica Nanoparticles with Optical Properties for Biomedical Applications

Abstract

Nanomedicine is the field of medical science that applies the knowledge and tools of nanotechnology to the prevention, diagnosis, and treatment of diseases. A variety of nanomaterials such as nanosheets, nanowires, nanorods, and nanoparticles have been studied for nanomedicine, but nanoparticles are considered as the most attractive material due to their high surface area to volume ratio and ability to be functionalized for imaging and targeted therapy. Until now, various types of nanoparticles such as metallic and non-metallic quantum dots, polymeric nanoparticles, magnetic nanoparticles have been studied and applied to biomedical fields of bio-imaging, biosensor, photothermal therapy, and drug delivery. Among various nanomaterials for biomedical applications, silica nanoparticles (SiNPs) have attracted much attention owing to their high biocompatibility, biodegradability, and functionality. Although the excellent applicability of SiNPs in biomedical fields has been proven, they still play a somewhat auxiliary role in biomedical applications because SiNPs generally have no direct function in clinical diagnosis. Previous researches have shown that silica can have optical properties by possessing optically active defects. Optically active defects generate intra-band gaps between the conduction and valence band of silica, allowing the silica to absorb and emit visible or infrared radiation. They can be controlled by synthesis conditions such as temperature, radiation, and atmospheric composition, so it is possible to produce desired defects with optical properties in SiNP through adjustment of synthesis conditions. This thesis reports the synthesis of SiNPs with optical properties through optically active silica defects generation and doping hetero atoms, and their applications in optical imaging, photoacoustic imaging, and sunblock agents. Hydrothermal synthesis method for the preparation of fluorescent SiNPs was developed using tetraethyl orthosilicate (TEOS) and (3-aminopropyl)trimethoxysilane (APTMS). The size and surface chemistry of the SiNPs could be controlled by varying the temperature and APTMS concentration, and synthesized SiNPs exhibited strong blue PL originating from the dioxasilyrane (=Si(O2)) and silylene (=Si:) defect centers with the aid of aminopropyl groups. The fluorescent SiNPs were successfully used for imaging of FL83B (mouse liver cell), A549 (human lung cancer cell), and Raw 264.7 (macrophage cell) cells without cytotoxicity. The emulsion-templated synthesis method was developed for the preparation of SiNPs with photoacoustic properties. For liver-specific delivery and imaging for the diagnosis of liver diseases, hyaluronate-silica nanoparticle (HA-SiNP) conjugates were synthesized. The HA-SiNP conjugates showed high liver-specific targeting efficiency, strong optical absorbance near-infrared windows, excellent biocompatibility, and biodegradability. The liver-specific targeting efficiency was verified by in vitro cellular uptake test and in vivo and ex vivo photoacoustic imaging, and photoacoustic amplitude in the liver injected with HA-SiNP conjugates was 4.4 times higher than that of the liver injected with SiNPs. The improved UV-absorbing SiNPs (BTBP-NPs) were synthesized for sunblock agent using 4,4′-Bis(triethoxysilyl)-1,1′-biphenyl (BTBP) as co-precursor with tetraethyl orthosilicate (TEOS). BTBP-NPs strongly absorbed the UVB region through the extended π-bonding system of the biphenyl group and also exhibited high reflectance at UVA due to the nature of the silica. Compared with other inorganic sunblock agents (titanium dioxide and zinc oxide nanoparticles), BTBP-NPs showed negligible reactive oxygen species (ROS) formation after UV exposure and its solution was less opaque due to the relatively low refractive index. Low skin penetration of BTB-NPs was confirmed through pig skin test using two-photon and fluorescence imaging, and UV protection and stability of BTBP-NPs were demonstrated by application to the skin of mice in vivo.