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Virus-Based Nanoparticles Cancer Drug Delivery

Czapar, Anna
http://rave.ohiolink.edu/etdc/view?acc_num=case1499438915195222

Abstract Details

, Doctor of Philosophy, Case Western Reserve University, Pathology.
Cancer is one of the leading causes of death in the world. Nanotechnology has emerged as one way to improve cancer patient survival; nanoparticles can carry large payloads of chemotherapeutics and can be engineered to accumulate preferentially in target solid tumors, limiting off-target adverse effects while overcoming development of drug resistance. Another avenue is the use of nanoparticles for immunotherapy – rather then delivering toxic payloads, immune-stimulatory agents are deployed to activate the body’s immune system against cancer. A wide range of nanoparticles, including synthetic and naturally occurring, have been investigated both for drug delivery and cancer immunotherapy in pre-clinical and clinical trials. My thesis focused on the development of plant viruses for drug delivery and immunotherapy, specifically I worked with the tobacco mosaic virus (TMV) and cowpea mosaic virus (CPMV). Compared to their synthetic counterparts as well as mammalian viral vectors, plant viruses have the advantage of having a high degree of quality control (genetically encoded materials are highly monodisperse) and of being non-infectious to mammals. The different size and shape of TMV and CPMV allows them to be utilized for different applications: I focused my efforts with TMV on drug delivery studies and developed CPMV as an immunotherapy approach. TMV is a rigid, rod-shaped virus (300 nm x 18nm); the high aspect ratio allows for enhanced tumor penetration and reduced immune cell uptake. My studies with TMV focused on developing this platform as a carrier for platinum chemotherapeutics for treatment of breast and ovarian cancer. To further improve the TMV-based drug delivery system, I investigated polymer coatings to avoid premature immune clearance. Next, I turned toward the icosahedral CPMV particles for cancer immunotherapy application making use of its natural immune stimulation. It has previously been shown that CPMV is a potent in situ vaccine, when administered intratumorally, CPMV primes an anti-tumor response. In this work, I developed a slow release formulation of the CPMV in situ vaccine to alleviate the need for repeat administration. Overall my work has expanded the understanding of plant viruses for cancer therapy in two areas: drug delivery and immunotherapy and provides a stepping-stone toward translation.
Nicole Steinmetz, PhD (Advisor)
Biomedical Research

Recommended Citations

Citations

  • Czapar, A. (n.d.). Virus-Based Nanoparticles Cancer Drug Delivery [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1499438915195222

    APA Style (7th edition)

  • Czapar, Anna. Virus-Based Nanoparticles Cancer Drug Delivery. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1499438915195222.

    MLA Style (8th edition)

  • Czapar, Anna. "Virus-Based Nanoparticles Cancer Drug Delivery." Doctoral dissertation, Case Western Reserve University. Accessed APRIL 24, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1499438915195222

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.