Gold nanoparticles (AuNPs) display unique characteristics compared to their macro-counterparts that are dependent on shape, size, and attached surface molecules. Methods have been developed to precisely control both size and shape of AuNPs for specific applications. The biocompatibility, plasmonic properties, and ease of functionalization with thiolated molecules, make gold nanoparticles attractive to a wide variety of biomedical fields, such as carriers for drug delivery and molecular sensing. This work focuses on the design and characterization of gold nanostars (AuNS) functionalized with thiolated DNA oligonucleotides for therapeutics.These AuNS are synthesized with a surfactantless method that yields a heterogenous mixture of shapes with a combination of positive, negative, and neutral curvatures. In Chapter 2, we explore how the negative curvature impacts the contrast enhancement of gadolinium-based of magnetic resonance imaging contrast agents, and the role the surrounding DNA plays. Building off previous work that had the Gd(III) chelate bonded to the DNA, a new chelate was synthesized to directly conjugate to the surface of the AuNS, which allows for the deconvolution of enhancement effects from both the nanostar and the surface DNA. Due to many of the properties of AuNS being dependent on shape and the synthesis resulting is a heterogeneous mixture, Chapter 3 investigates both pre- and post-synthesis shape determinants. Despite the AuNS deriving from only two precursors, the Good’s buffer HEPES and the gold salt (HAuCl4), and no seed precursor, little is known about what dictates the final shape or why some batches of AuNS do not form. Here, we look into how the oxidation state of the HEPES buffer affects the shape population. Then, we investigate the ability of the AuNS to maintain their distinctive sharp branch tips when exposed to environmental stressors – heat and light irradiation – and how attached surface molecules act as a protectant against particle reshaping. Since many of the biological applications are dependent on the surface molecules interacting with the surrounding environment, placement on the AuNS is critical to the design of the nanoconstruct. If a DNA oligo is required to bind to a cellular receptor, being located in the sterically hindered negative curvature could prevent NP-receptor interactions. Chapter 4 explores characterization methods of molecules bound to the surface of AuNS with Au-S chemistry. The size of nanoparticles often requires measurements of the bulk solution, however, here we use techniques for single-NP characterization. Finally, in Chapter 5, we delve into the design of AuNS for therapeutic cancer vaccines. Because oligonucleotide-coated AuNPs enter cells without transfection agents, they are an ideal delivery agent for both the adjuvant and antigen components of a vaccine. As a therapeutic vaccine instead of prophylactic, the construct is required to contain all elements necessary to re-train the immune system to attack cells labeled as “self”, without over-stimulating the immune system and creating adverse reactions. Here, we develop a TLR9-targeted construct to activate the immune system and a platform to selectively functionalize only the tips of AuNS branches with the immunogenic DNA sequence.

Creator

• Coughlin, Emma

DOI

• https://doi.org/10.21985/n2-5kcc-n257

Subject

• Nanotechnology
• Chemistry
• Biology

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:15532
• etdadmin_upload_815702

Keyword

• gold nanopaticles
• therapeutics
• DNA
• cancer vaccine
• plasmonics

Date created

• 2021-01-01

Resource type

• Dissertation

Rights statement

• In Copyright