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Influence of PEG Conformation on Efficacy of Silica Nanoparticle Immunotherapy for Metastatic Tumors

Becicka, Wyatt Morgan
http://rave.ohiolink.edu/etdc/view?acc_num=case1605201031658173

Abstract Details

2020, Master of Sciences, Case Western Reserve University, Biomedical Engineering.
Although the average cancer mortality rate has steadily declined over the past 25 years, the majority of advanced disease remains resistant to current treatment methods and yields dismal prognoses.1 Novel immunotherapies such as CAR T-cell transfer therapy and ICB provide promising avenues to overcome tumor-mediated immune evasion and initiate an adaptive immune response towards cancer cells. The strongly immunosuppressive microenvironment in advanced tumors, however, can limit the downstream potential of these therapies, and to date these therapies have provided mixed clinical results.2,3 In an attempt to reverse the immunosuppressive tumor microenvironment, we have designed a MSN that can traffic a STING agonist—cdGMP—into innate immune cells and produce a nearly 9-fold increase in pro-inflammatory IFN-𝛽 secretion compared to the free agonist. In a metastatic 4T1 model, the surface density of PEG molecules dictates what innate immune cells have access to systemically injected MSNs. Following treatment with cdGMP-loaded MSNs, this differential distribution and uptake of particles leads to differences in innate immune cell recruitment at metastatic sites and in the blood. It is displayed that an immunostimulatory nanoparticle can be engineered to enhance innate immune cell activation in advanced, metastatic disease, providing a tool that may be able to work in combination with other current immunotherapies to yield more robust and consistent therapeutic responses.
Efstathios Karathanasis, PhD (Committee Chair)
David Wald, MD-PhD (Committee Member)
Horst von Recum, PhD (Committee Member)
40 p.
Biomedical Engineering
Cancer immunotherapy; mesoporous silica nanoparticle; systemic drug delivery; STING agonist; PEG

Recommended Citations

Citations

  • Becicka, W. M. (2020). Influence of PEG Conformation on Efficacy of Silica Nanoparticle Immunotherapy for Metastatic Tumors [Master's thesis, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1605201031658173

    APA Style (7th edition)

  • Becicka, Wyatt. Influence of PEG Conformation on Efficacy of Silica Nanoparticle Immunotherapy for Metastatic Tumors. 2020. Case Western Reserve University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1605201031658173.

    MLA Style (8th edition)

  • Becicka, Wyatt. "Influence of PEG Conformation on Efficacy of Silica Nanoparticle Immunotherapy for Metastatic Tumors." Master's thesis, Case Western Reserve University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1605201031658173

    Chicago Manual of Style (17th edition)

case1605201031658173
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© 2020, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.