Nanotechnologies and chemical tools for cell biology

This dissertation describes several nanotechnologies and chemical tools that I have developed to probe living cells.; Chapter one gives a brief overview on the current status of biomedical and biotechnological applications of carbon nanotubes (CNTs). In this chapter, strategies for functionalization of CNTs with emphasis on biological applications are reviewed. Representative developments in biosensing, bioimaging, intracellular delivery, and tissue engineering are presented. Recent studies on toxicity of CNTs are also discussed.; Chapter two describes the development of a nanoscale cell injector for delivery of cargo to the interior of living cells without physiological harm. A CNT attached to an atomic force microscope tip was functionalized with cargo via a disulfide linker. Penetration of cell membranes with this "nanoneedle", followed by reductive cleavage of the disulfide bonds within the cell's interior, resulted in the release of cargo inside the cells.; Chapter three presents a biomimetic functionalization strategy for interfacing CNTs with biological systems. The potential biological applications of CNTs have been limited by their insolubility in aqueous environment and their intrinsic toxicity. We developed a biomimetic surface modification of CNTs using glycosylated polymers designed to mimic natural cell surface mucin glycoproteins interactions.; Chapter four further extends the biomimetic strategy for functionalization of CNTs to glycosylated dendrimers. We developed a new class of amphiphilic bifunctional glycodendrimers that comprised carbohydrate units displayed in the periphery and a pyrene tail that bound to SWNT surface via pi-pi interactions. The glycodendrimer-coated CNTs were soluble in water, and noncytotoxic. We also demonstrated that the coated CNTs could interface with biological systems including proteins and cells.; Chapter five presents a biosensing application of glycodenderimer-coated CNTs. SWNTN-FETs coated with glycodendrimers were shown to specifically recognize target lectins. This label-free electronic detection using SWNTN-FETs might be further explored for sensing of bacteria and viruses.; Chapter six describes the cytotoxicity studies of boron nitride nanotubes (BNNTs) and their biological applications. Here we report that boron nitride nanotubes (BNNTs), isosteres of CNTs with unique physical properties, are inherently noncytotoxic. Furthermore, BNNTs can be surface functionalized with biological epitopes that mediate protein and cell binding. Finally, we show that BNNTs can deliver DNA oligomers to the interior of cells with no apparent toxicity.; Chapter seven presents a metabolic oligosaccharide engineering approach towards boron neutron capture therapy (BNCT). Here we present a strategy for the selective delivery of BNCT reagents to tumor cells that exploits intrinsic differences in sialic acid expression. (Abstract shortened by UMI.)...