Wilhelm, StefanFrickenstein, Alex2023-08-022023-08-022023-08-04https://shareok.org/handle/11244/338768Mechanisms of nanoparticle-cell interactions are dependent upon the size of the administered nanoparticles. At pre-clinical and clinical levels, precise control over the size and monodispersity of nanoparticles is required to produce consistent, effective, well-understood results. Gold nanoparticles (AuNPs) are a commonly used model nanoparticle for understanding nano-bio interactions based on AuNPs relative ease of synthesis and characterization. While ensemble characterization methods of AuNPs made using citrate-based synthesis approaches indicate relative size monodispersity, single nanoparticle analytical techniques reveal a wide size distribution. This wide size distribution decreases confidence in exact size-interaction correlations within nano-bio interactions and confounds sensitivity of single nanoparticle analysis. There is a need for AuNPs possessing a lower size distribution for improving single cell and single nanoparticle analyses of nano-bio interactions. In the current dissertation, single particle inductively coupled mass spectrometry (SP-ICP-MS) is used to characterize AuNPs synthesized using two different synthesis methods – citrate-based and CTAC-based – to identify differences in size monodispersity. Our analysis confirmed that CTAC-based AuNPs possess a tighter size distribution compared to citrate-based AuNPs. SP-ICP-MS was used to assess size prediction and synthesis scale-up models for each of the two synthesis methods. Further, AuNP growth kinetics of CTAC-based synthesis were characterized. AuNPs synthesized using CTAC-based methods are innately cytotoxic, making them unfit for biomedical use immediately after synthesis. To overcome this challenge, different methods of surface modification were developed that improved biocompatibility and biofunctionalization of CTAC-based AuNPs. SP-ICP-MS measurements confirmed that surface modification strategies did not result in a change in monodispersity, maintaining a tight size distribution for CTAC-based AuNPs. Biocompatible, biofunctional CTAC-based AuNPs were compared to citrate-based AuNPs in cell viability, cell uptake, and surface ligand interaction experiments. The overall findings of these results provide tools and methods by which highly monodisperse AuNPs may be synthesized, modified, and applied to better understand nano-bio interactions. Further, these results illuminate the possibilities and advantages of applying biocompatible monodisperse AuNPs in nanomedicine.Inorganic Nanoparticle SynthesisSingle Nanoparticle Mass SpectrometryNanoparticle Monodispersity