Deciphering the targets of axonal projections plays a pivotal role in interpreting neuronal function and pathology. Neuronal tracers are indispensable neurobiology tools for elucidating advanced functions and interactions between different subregions of the brain. Commercially available neuronal tracers include small molecule dyes, viruses, and synthetic nanoparticles. Among these options, viral tracers raise concerns because of their inherent belligerent and aberrant activity. In addition, the commonly used non-viral retrograde tracers in the field, such as Cholera toxin subunit B (CTB) and Fluoro-gold (FG), are natural products and thus have not been subjected to serial structure optimization. Moreover, non-viral vectors are gathering more attention as they have tunable chemical parameters to fulfill a variety of physiological demands. However, there is no non-viral vector material available on the market with the capability of both neuronal tracing and gene delivery. Therefore, this thesis explores novel polymeric retrograde nano-tracers as neuronal tracers and vectors. This thesis describes the synthesis and characterization of polymeric retrograde neuronal tracers and vectors. First, a rainbow of polymeric nanoparticle neuronal tracers (NNTs) is harnessed by emulsion polymerization, allowing for up to 4 fluorophores to be used in neuronal tracing concurrently. An empirical optimization of synthetic conditions and monomer compositions is described. Next, in vitro studies demonstrate a comprehensive understanding of the cellular uptake mechanisms of NNTs and provide a guideline for further in vivo analysis. In vivo studies confirm the efficacy and feasibility of NNTs and illustrate a proof-of-concept to utilize the emulsion polymerization in generating modular neuronal tools for biological studies. Next, two novel DOTA-based magnetic resonance imaging (MRI) contrast agents are developed for the NNT system as an additional function to the rainbow of fluorescence labels. Lastly, different design strategies of nanocapsules are described towards the selective transport of therapeutic agents in neurons.

Creator

• Zang, Nanzhi

DOI

• https://doi.org/10.21985/n2-abdx-fn87

Subject

• Chemistry

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:15029
• etdadmin_upload_723830

Date created

• 2019-01-01

Resource type

• Dissertation

Rights statement

• In Copyright