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Towards Bioactive Rosette Nanotubes for Biomedical Applications

  • Author / Creator
    Alsbaiee, Alaaeddin
  • Rosette nanotubes (RNTs) are bio-inspired nanomaterials generated from the self-assembly of a guanine-cytosine motif called the “G∧C” base. These nanotubular architectures are promising 2-D coating materials for bone tissue engineering applications, and delivery scaffolds for hydrophobic drug molecules in physiological media. For successful biomedical applications of RNTs however, it is necessary to: 1) explore the extent to which peptides on their outer surface can be tolerated, 2) develop radiolabeling methods to facilitate in vivo studies, and 3) extend the RNT inner diameter for enhanced drug encapsulation capability. This thesis aims to provide physical and synthetic tools in which to expand the scope of the RNTs for biomedical applications, particularly within the areas of bone tissue engineering and drug delivery. Chapter 1 provides a literature review of self-assembled nanomaterials that are based on bio-inspired building blocks including peptides and nucleic acids and are currently being investigated for biomedical applications. Given the importance of functionalizing such nanomaterials with peptides, Chapter 2 aims to demonstrate that RNTs can act as a scaffold to express three bioactive 11-amino acid-long peptides named A, B and C. Specifically, the synthesis and self-assembly of peptides (A-C)-functionalized twin G∧C motifs, (pA-TB, pB-TB and pC-TB) and a lysine-functionalized motif K1-TB, are presented. Next, three co-assembled RNT-constructs consisting of 90% of K1-TB and 10% of each of the peptide-TB conjugates are prepared. Circular dichroism in combination with microscopy techniques, provide evidence for the first time of the formation of bi-functionalized RNTs having a random mixed configuration. Chapter 3 introduces two radiolabeling strategies of RNTs for single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging techniques. In these strategies, the synthesis and self-assembly of RNTs, which are functionalized with an oxo-rhenium complex (for SPECT) and p-fluorobenzoate (for PET) are presented. Next, Chapter 4 describes a 13-step synthetic strategy to obtain an organic-soluble tetracyclic yG∧C motif for self-assembly into RNTs with a ca. 1.7 nm inner diameter for drug delivery applications. The self-assembly of this motif is then investigated using microscopy techniques. Finally, Chapter 5 highlights the significance and future directions of this work

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3F97N
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Chemistry
  • Supervisor / co-supervisor and their department(s)
    • Co-supervisor: West, Frederick G (Department of Chemistry)
    • Supervisor: Fenniri, Hicham (Department of Chemistry)
  • Examining committee members and their departments
    • Campbell, Robert E (Department of Chemistry)
    • Lowary, Todd (Department of Chemistry)
    • Petersen, Nils (Department of Chemistry)
    • MacLachlan, Mark (Department of Chemistry, University of British Columbia)