TOPOLOGICAL ENGINEERING AND SURFACE CHEMISTRY OF ULTRASMALL FLUORESCENT SILICA NANOPARTICLES FOR CANCER NANOMEDICINES

Abstract

In the evolution of life on earth, complex biological molecules, viruses, and microorganisms have first emerged. The fascinating complexity of these biological structures at the nanoscale, with topologies varying from spheres to icosahedral objects to rings and with different surface chemistries, have always been an inspiration to scientists from a number of disciplines. Although the role of such topologies and respective surface chemistries on modulating biological response is still an open question, there have been numerous efforts in both synthesizing such nanoscale structures and their applications in medicine, particularly cancer diagnostics and therapeutics. In this dissertation, ultrasmall fluorescent silica nanoparticles with diameters around 10 nm and spherical, dodecahedral, and torus-type topologies are investigated. First, orthogonal pathways for surface functionalization of inside and outside surfaces of torus-shaped ultrasmall silica nanoparticles are explored using high-performance liquid chromatography (HPLC). Second, the formation mechanisms of ultrasmall spherical silica nanoparticles are investigated in order to minimize surface chemical heterogeneities as detected by HPLC that result from incomplete covalent encapsulation of fluorescent dye molecules. Finally, in-vivo studies in mice elucidate the effects of nanoparticle topology on pharmacokinetics and biodistribution. Results suggest synthetic pathways to next generation nanomaterials for advanced applications in bioimaging and nanomedicine.