Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology
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Case Western Reserve University School of Graduate Studies / OhioLINK
2016
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case14529545112021-08-03T06:34:50Z Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology Wen, Amy M. Biomedical Engineering Nanotechnology plant virus nanoparticle nanomedicine bioconjugation encapsulation optical imaging MR imaging photodynamic therapy dendrons tropism aspect ratio shape targeting thrombosis 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. 2016-05-31 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511 http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Engineering Nanotechnology plant virus nanoparticle nanomedicine bioconjugation encapsulation optical imaging MR imaging photodynamic therapy dendrons tropism aspect ratio shape targeting thrombosis |
| spellingShingle |
Biomedical Engineering Nanotechnology plant virus nanoparticle nanomedicine bioconjugation encapsulation optical imaging MR imaging photodynamic therapy dendrons tropism aspect ratio shape targeting thrombosis Wen, Amy M. Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology |
| author |
Wen, Amy M. |
| author_facet |
Wen, Amy M. |
| author_sort |
Wen, Amy M. |
| title |
Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology |
| title_short |
Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology |
| title_full |
Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology |
| title_fullStr |
Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology |
| title_full_unstemmed |
Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology |
| title_sort |
engineering virus-based nanoparticles for applications in drug delivery, imaging, and biotechnology |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2016 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511 |
| work_keys_str_mv |
AT wenamym engineeringvirusbasednanoparticlesforapplicationsindrugdeliveryimagingandbiotechnology |
| _version_ |
1719439501987676160 |