Functionalized Silicon-based Porous Nanomaterials And Their Drug Delivery Property

Rapid advances in nanotechnology have provided new opportunities for a variety of disciplines. Nanostructured materials have emerged as novel bioimaging, diagnostic, and therapeutic agents for the future medical field. In the latest decades, the drug delivery system based on nanocarriers has attracted much attention. Nanocarriers can be used to increase local drug concentration by carrying the drug within and control-releasing it when bound to the targets, and then greatly enhancing the therapeutic index of the drugs. The family of nanocarriers includes polymer conjugates, polymeric nanoparticles, lipid-based carriers such as liposomes and micelles, dendrimers, carbon nanotubes, and inorganic nanoparticles etc. Among these nanoscopic therapeutic systems, silicon-based porous materials, have emerged as an innovative nanovectors for drug delivery due to their remarkable biocompatibility, biodcgradability, case of functionalization and many other fascinating features. In this thesis, we designed and prepared kinds of functionalized silicon-based porous materials as nanocarriers of drug delivery.In the last two decades, efforts have mainly been focused on the study of porous silica and metal-based compounds; however, porous silicon related materials are rarely investigated. In fact, porous silicon as one of the most important semiconductor has found the significant way in many fields such as microelectronics, photocatalysts, and biological/chemical sensing. In chapter two, we have demonstrated a strategy to prepare mesoporous silicon from parent mesoporous silica via magnesiothermic reduction. The resulted mesoporous silicon possesses uniquemesopores itself. Another feature of as-prepared mesoporous silicon is that they exhibit high surface area, high crystallinity and preserve the same morphology of mesoporous silica precursors. Besides, these materials may hold immense promise in drug delivery system and intrigue interest in studies of semiconductor. Moreover, the present strategy will provide an effective way to the targeted synthesis of mesoporous silicon-based materials for further applications.The mesoporous silica have been promising in many fields including catalysis, separation science and sensors due to their unique and advantageous structural properties, such as high surface area and pore volume, stable mesostructure, tunable pore diameter and modifiable morphology. And then this triggered widely research interest on the fabrication of mesoporous silica based drug delivery system as well. Recently, the development of gated stimuli-responsive drug delivery system based on mesoporous silica is a new research field. To date, different gated structures have been reported that contain, which in most of cases use pH, rcdox changes, and light as trigger for uncapping the pores. Out of these applied stimuli, a more effective strategy to accomplish fast-cytoplasmic drug release to cancer cells will be to employ pH responsive nanoparticles as drug vehicles due to the acidic extracellular and intracellular environment of cancer cells. In chapter three, acid-decomposable, luminescent ZnO quantum dots (QDs) have been employed to seal the nanopores of mesoporous silica nanoparticles (MSNs), loaded with antineoplastic drug doxorubicin (DOX), to inhibit the premature drug release. After being internalized into lysosomes of HeLa cells, these ZnO QD lids arc instantly dissolved and in turn the loaded DOX is readily released to the cytosols from the MSNs and resultantly kill the cancer cells. ZnO QDs not only act as a cap but also exhibits synergistic antitumor activity. We anticipate that these unprecedented nanoparticles may prove a significant step towards the development of a pH-sensitive drug delivery system to minimize the drug toxicity.Recently, multifunctional nanostructured materials that combinations of various different properties have been applied to multimodal imaging and simultaneous diagnosis and therapy. Halloysite nanotubes (HNTs), a type of aluminosilicate clay mineral, having a hollow tubular structure in the submicron range, are increasingly becoming the focus of investigations. Due to its biocompatibility and very low cytotoxicity as demonstrated in cell growth experiments, hence, HNTs qualified a promising candidate for nanomedicine. In chapter four, we devised a facile strategy to utilize multifunctional halloysitc nanotubes as nanovector for anticancer drug delivery. Tumor cell targeting molecules folic acid (FA, a nonimmunogenic receptor-specific ligand) and magnetic nanopartieles were tethered to the halloysite nanotubes via a facile EDC chemistry. Furthermore, this multifunctional nanoformulation exhibited pH-sensitive drug release behavior due to electrostatic interaction between the drug and HNTs. It is expected that this orchestrated system may provide a more effective tool for targeted cancer therapeutics.