Nanomaterials are increasingly incorporated in modern day life, from the biogenic viruses that cause pandemics and the mineral crystallites embedded alongside collagen in our bones, to the anthropogenic nanomaterials that are small but powerful components of sunscreen and paint, swimming pool algaecides and wound dressings, cancer treatments, bicycle frames, and chewing gum. With their highly tunable properties and wide range of applications, nanomaterials are only likely to become more ubiquitous, and accordingly, so too will their interactions with biology. Imaging and otherwise characterizing these interfaces, between materials of highly dissimilar properties, presents many unique challenges; however, expanding our knowledge of these interactions is critical to enhancing understanding of biological development for synthesis of improved materials, and for illuminating the complex interactions between human tissue and exogenous nanomaterials — whether they appear in the environment or deliberately delivered as medicine. In this thesis, we explore the application of advanced materials characterization techniques to the nanomaterial-tissue interface. We first employ several EM-based methods to study the formation of calcite spicules in sea urchins, constructing a correlative cryo-fluorescence/cryoSEM system and identifying ultrastructural features caused by VEGF exposure in vitro. Second, we establish a multi-scale imaging platform that can be used to evaluate delivery of nanotherapeutics to cells and solid tumors. We demonstrate proof-of-concept in an analysis of platinum-stabilized arsenic-loaded ‘nanobins’, as delivered to a patient derived xenograft model of glioblastoma (GBM). Using MRI, fluorescence imaging, TEM, LA-ICP-MS, synchrotron XRF, cryogenic X-ray nanotomography, and XANES, we show that NBs are successfully delivered to the brain and GBM tumors, are internalized within cells, and may enter cell nuclei. XANES reveals differential processing of arsenic in regions of low and high arsenic content in brain tissue, and that arsenic glutathione is a major metabolite in cells. We further illustrate that arsenic and platinum are transported differently in the cell due to endosomal recycling, implying that arsenic, the primary cytotoxic agent, escapes the endosomal pathway, which limits the delivery of many nanotherapeutics. Our platform is highly generalizable and may be easily extended to other nanomaterial/cancer systems, thus offering a systematic approach to expedite translation of nanomaterials to the clinic.

Creator

• DiCorato, Allessandra Elizabeth

DOI

• https://doi.org/10.21985/n2-wghz-4631

Subject

• Nanoscience
• Materials Science

Language

• en

Alternate Identifier

• etdadmin_upload_843461
• http://dissertations.umi.com/northwestern:15714

Date created

• 2021-01-01

Resource type

• Dissertation

Rights statement

• In Copyright