Engineering the interfaces between biomolecules and nanomaterials is central to the creation of materials for diverse areas of biomedical applications, including therapy, sensing and imaging. The goal of this research has been oriented toward the tailoring of the interfaces through the atomic level control provided by the organic synthesis. By employing a synergistic approach in the research, combining colloids, surface science, organic synthesis and biology, gold nanoparticles with tailored monolayers have been developed for bio-applications. This thesis illustrates the design and synthesis of these surface functionalized gold nanoparticles and their use in protein surface recognition and delivery systems for therapeutic applications. For protein surface recognition, we have fabricated gold nanoparticles bearing a diversity of amino acids termini and studied their interactions with proteins to elucidate the parameters affecting their interactions and catalytic behavior. In therapeutic applications, we have demonstrated the use of organically tailored nanoparticles for the creation of delivery systems featuring tunable stability and regulated drug release. Additionally, gold nanoparticles functionalized with molecular recognition motif have been used to demonstrate host-guest chemistry inside the living cells for the activation of therapeutic gold nanoparticles.

Self-assembly of nanoparticles presents an excellent tool in the development of novel nanoscale structures and materials for creating high sensitive sensors, electronic and diagnostic devices, ultrahigh-density magnetic storage devices and many more. In these systems, the nanoparticle core imparts exceptional physical properties while their organic coatings regulate the assembly process. Moreover, organic coatings improve particle stability and solubility, as well as regulate charge and hydrophobicity. This thesis has focused on the engineering of nanoparticles’ surfaces using organic molecules and assembly of these particles through supramolecular interactions for various applications. Morphology of the nanoparticle assembly was tuned simply by varying the degree of fluorinated coating on particles’ surfaces and thus controlling their hydrophobicity. Surface engineered particles were also assembled at oil-water interfaces alone and with enzymes creating colloidal microcapsules for controlled release and catalysis respectively. The combination of the unique attributes of the nanoparticle cores and the function of the organic coating provides ample opportunities in the creation of multi-functional nano-materials that are useful in biological and materials applications.

Over the past few decades, tremendous efforts have been made to develop nanomaterials for biotechnological applications such as therapeutics. Understanding and engineering interfaces between biomacromolecules and nanomaterials is a key to the creation of successful therapeutic systems. My research has been oriented toward developing therapeutic systems using gold nanoparticles (AuNPs) incorporating material science, organic synthesis, and biology. For this purpose, mixed monolayer protected AuNPs (∼2 nm core size) with various functional groups have been employed for triggering therapeutic effects. Several strategies have been accomplished using anticancer drugs that non-covalently and covalently incorporate onto AuNPs as a drug delivery carrier. Alternatively, AuNPs were developed by regulating host-guest complexation processes inside the cell, allowing control of the therapeutic effect of the AuNP. In addition, by using host-guest chemical events on the AuNPs, exocytosis of the AuNPs was controlled, enabling their prolonged retention inside of the cells, providing new strategies for improving conventional drug delivery systems. Therefore, engineering of the AuNP surface can afford new pathways for designing and improving therapeutics.

Monolayer protected nanoparticles (NPs) include an inorganic core and a monolayer of organic ligands. The wide variety of core materials and the tunable surface monolayers make NPs promising materials for numerous applications. Concerns related to unforeseen human health and environmental impacts of NPs have also been raised. In this thesis, new analytical methods based on mass spectrometry are developed to understand the fate, transport, and biodistributions of NPs in the complex biological systems. A laser desorption/ionization mass spectrometry (LDI-MS) method has been developed to characterize the monolayers on NP surface. LDI-MS allows multiple NPs taken up by cells to be measured and quantified in a multiplexed fashion. The correlations between surface properties of NPs and cellular uptake have also been explored. LDI-MS is further coupled with inductively coupled plasma mass spectrometry (ICP-MS) to quantitatively measure monolayer stability of gold NPs (AuNPs) and quantum dots (QDs), respectively, in live cells. This label-free approach allows correlating monolayer structure and particle size with NP stability in various cellular environments. Finally, uptake, distribution, accumulation, and excretion of NPs in higher order organisms, such as fish and plants, have been investigated to understand the environmental impact of nanomaterials. The results indicate that surface chemistry is a primary determinant. NPs with hydrophilic surfaces are substantially less toxic and present a lower degree of bioaccumulation, making these nanomaterials attractive for sustainable nanotechnology.