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Halley - Masters Thesis - 3.pdf (48.59 MB)

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DNA Origami as a Drug Delivery Vehicle for in vitro and in vivo Applications

Halley, Patrick D
http://rave.ohiolink.edu/etdc/view?acc_num=osu1480632777328142

Abstract Details

2016, Master of Science, Ohio State University, Chemical Engineering.
DNA origami nanostructure technology allows for the precise control of size and structure formation using the building blocks of life. Here, DNA was not used as the blueprint for protein formation but as a delivery vehicle for chemotherapeutic drugs, such as the anthracycline antibiotic, daunorubicin. By itself, daunorubicin has limited pharmacokinetics and biodistribution profiles when applied in vivo. In addition, daunorubicin, like most small molecule drugs, is ineffective against cancer cells that have acquired multi-drug resistance (MDR). By delivering the chemotherapeutic using DNA origami allows the drug to travel through the endolysosomal pathway, bypassing MDR mechanisms. Here, we were able to overcome MDR mechanisms in a liquid tumor cell line using the “Trojan Horse” DNA origami nanostructure as a drug delivery vehicle. Though promising, there are many barriers to pass before DNA origami nanostructures is a viable option for clinical use. This includes commercial level scale-up, target specificity and testing for immunogenicity and toxicity in vivo. Here, we discuss a method developed for the scale up of DNA origami production by 1500x standard volumetric reaction amounts. In addition, we were able to characterize a multitude of nanostructures for a more universal scaled process. Furthermore, we measured the effects that high concentrations of DNA origami nanostructures have in a mouse model. Lastly, since the binding and subsequent cellular internalization of DNA origami is non-specific, we were able to attached strategically located antibodies allowing for not only targeted drug specificity, but also blocking non-specific cell uptake. With these additions, the hope is that effective chemotherapeutics can be delivered to tumor sites while avoiding undesirable damage to healthy tissues in a clinical setting.
Carlos Castro (Advisor)
160 p.
Biomedical Engineering; Biomedical Research; Chemical Engineering; Nanoscience; Nanotechnology; Oncology; Pharmaceuticals
nanotechnology; DNA origami; DNA nanostructures; Drug Delivery; AML; Fabrication; Chemotherapy; Trojan Horse; MDR; Multi drug resistance; best; in vivo; immunogenicity; toxicity; targeted; therapy; antibody

Recommended Citations

Citations

  • Halley, P. D. (2016). DNA Origami as a Drug Delivery Vehicle for in vitro and in vivo Applications [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480632777328142

    APA Style (7th edition)

  • Halley, Patrick. DNA Origami as a Drug Delivery Vehicle for in vitro and in vivo Applications . 2016. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1480632777328142.

    MLA Style (8th edition)

  • Halley, Patrick. "DNA Origami as a Drug Delivery Vehicle for in vitro and in vivo Applications ." Master's thesis, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480632777328142

    Chicago Manual of Style (17th edition)

osu1480632777328142
143
© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.