Functionalised silica coated nanoparticle hybrids for drug delivery and imaging
Date of Issue2013
School of Physical and Mathematical Sciences
In recent years, nanoparticles have been extensively explored for biomedical applications due to their unique properties. Among various nanomaterials, silica-based nanoparticles exhibit superior biocompatibility which attracted much research attention. These particles also provide several advantages such as large functional surface, tunable structures and high spectroscopic transparency. In this research dissertation, we focused on developing novel and convenient drug delivery systems for theranostic applications based on silica-coated nanoparticles. Taking the advantage of functional surface structure property of silica nanoparticles, we designed a silica-coated magnetic nanoparticle platform that doxorubicin-peptide conjugated to the surface through “click” chemistry. The chosen peptide could be cleaved by enzyme which only found in the intracellular compartment. This conjugate nanoparticle system demonstrated highly efficient drug release upon enzyme interactions in vitro and in living cells. This system also showed multiple functions that drug release in the selected cells, fluorescence imaging and magnetic resonance imaging. Since silica nanoparticles exhibit good biocompatibility and high spectroscopic transparency, we employed silica-coated upconversion nanoparticles for light-induced therapeutic agents release in the following chapters. By linking the caged D-luciferin to the particles surface, the obtained conjugates can serve as promising platforms for the near-infrared light-responsive bioluminescent molecules release. This approach takes advantage of upconverted UV emission of upconversion nanoparticles from near-infrared light excitation to trigger the uncaging of D-luciferin from the nanoparticle conjugates. Furthermore, the release process can be monitored either by tracking the enhanced fluorescence intensity of D-luciferin or by measuring the bioluminescence signals in vitro and in vivo. The use of silica-coated upconversion nanoparticles can be extended to gene delivery. The particles functionalized with cationic photocaged linker were used as nanocarriers for siRNA delivery to effectively silencing enhanced green fluorescent protein gene expression. siRNA was adsorbed on the platform through electrostatic attractions which was easily internalization by cells. The release process was initiated by the upconverted UV light from upconversion nanoparticles under near-infrared light exposure. As we known, silica-based nanoparticles have two major types, solid silica nanoparticles which we have been used to coat inorganic core nanoparticles in the previous work, the other one is mesoporous silica nanoparticles.