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Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology

Wen, Amy M
http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511

Abstract Details

2016, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Nanomedical approaches are of great interest due to their potential for specifically delivering packaged contrast agents and drugs to sites of disease while avoiding healthy tissue. Non-mammalian viruses, which are noninfectious to humans, can be used as unique nanoscale scaffolds with many advantages for nanotechnology and biomedicine. Compared to synthetically programmed materials, these particles can be precisely arranged into a diverse array of shapes and sizes, and there are many available avenues for easy and reproducible modification. Here, I investigated the expansion of the potential of these viruses for diverse applications in nanomedicine. First, I demonstrated the capability for interior engineering of a well-known icosahedral plant virus, cowpea mosaic virus (CPMV), for the encapsulation of a range of molecules, including fluorophores to enable optical imaging in the setting of cancer detection and diagnosis. Then, some design considerations were examined for the use of nanoparticles for fluorescence imaging, which informed our choices for subsequent studies. Dye density, dye localization, conjugation method, and cell uptake were all found to affect the resultant fluorescence intensity with the optimal design parameters being: non-aromatic linker chemistries, exterior particle conjugation, and dye spacing of around 8-10 nm. A second set of studies explored drug delivery using virus-based particles, demonstrating their utility for photodynamic therapy through solubilization of highly hydrophobic photosensitizers as well as for the treatment of chronic infections through using their native tropism. Finally, as increasing evidence suggest that shape is an important parameter for cell and tissue interactions, we explored the effect of aspect ratio and shape in mediating cell uptake and targeting the vessel wall. Nanoparticle chains were created, with clear differences seen in cell uptake due to shape-based as well as avidity effects. Additionally, in a parallel investigation, rod-shaped particles were shown to be better able to marginate to the side of the vasculature and bind to sites of thrombosis. For more specific thrombus targeting, peptides with affinity for a mediator of thrombosis were identified and investigated for their potential to enhance particle binding to thrombi. Overall, my research spanned the imaging and treatment of cancer, infectious disease, and cardiovascular disease and added to the possibilities of using virus-based particles for future biomedical applications.
Horst von Recum, Ph.D. (Committee Chair)
Nicole Steinmetz, Ph.D. (Advisor)
Stuart Rowan, Ph.D. (Committee Member)
Daniel Simon, M.D. (Committee Member)
370 p.
Biomedical Engineering; Nanotechnology
plant virus; nanoparticle; nanomedicine; bioconjugation; encapsulation; optical imaging; MR imaging; photodynamic therapy; dendrons; tropism; aspect ratio; shape; targeting; thrombosis

Recommended Citations

Citations

  • Wen, A. M. (2016). Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511

    APA Style (7th edition)

  • Wen, Amy. Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology. 2016. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511.

    MLA Style (8th edition)

  • Wen, Amy. "Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511

    Chicago Manual of Style (17th edition)

case1452954511
409
© 2016, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.