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The Designs, Syntheses and Medical Applications of Mesoporous Silica Nanoparticle Based Drug Delivery Systems

Abstract

The work covered in this thesis focuses on the development of mesoporous silica nanoparticle-based platforms for the controlled delivery of therapeutic agents. The first part of the thesis discusses the physical chemical properties of mesoporous silica nanoparticles, including the studies on their uptake and release capacities and the physical states of the encapsulated cargo molecules using spectroscopic methods. The second part of the thesis describes the organic functionalizations of the mesoporous silica nanoparticles with novel cyclodextrin-based nanogate systems, achieving pH and redox responsive controlled release mechanisms, as well as cargo size selectivity for the release from a dual-loaded system. In the third part of this thesis, several examples of the biomedical applications of the mesoporous silica nanoparticle based drug delivery systems are shown. This includes the in vitro delivery of small interference RNA to shutdown endogenous and exogenous gene expressions in cells using the polyethyleneimine coated nanoparticles, the in vivo delivery of anti-cancer therapeutic to achieve tumor suppression effects on mice models, and the in vivo delivery of anti-microbial therapeutic to achieve animal protection from anthrax lethal toxins. A combination of all these areas of research demonstrate the advancement of the mesoporous silica nanoparticle based drug delivery system towards utilization within living organisms, and realization of medicine on the nanoscale.

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