ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: chemical engineering
- Creators: Acharya, Abhinav P
Description
Drug delivery has made a significant contribution to cancer immunotherapy and can have a tremendous impact on modulating immunometabolism, thereby affecting cancer outcomes. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. For example, cancer vaccines require activation of dendritic cells (DCs) and tumour associated Mɸs (TAMs) through modulation of their energy metabolism (e.g., glycolysis, glutaminolysis, Krebs cycle). Similar to activated immune cells, cancer cells also upregulate glucose and glutamine transporters for proliferation and survival. Cancer cells having accelerated energy metabolism, which has been exploited as a target for various therapeutic studies. In the first strategy, an immunometabolism strategy based on sustained release of succinate from biomaterials, which incorporate succinate in the backbone of the polymer was developed. This study demonstrates that succinate-based polymeric microparticles act as alarmins by modulating the immunometabolism of DCs and Mɸs to generate robust pro-inflammatory responses for melanoma treatment in immunocompetent young as well as aging mice. In the second strategy, a biomaterial-based strategy was developed to deliver metabolites one-step downstream of the node where the glycolytic pathway is inhibited, to specifically rescue DCs from glycolysis inhibition. The study successfully demonstrated for the first time that the glycolysis of DCs can be rescued both in vitro and in vivo using a biomaterial strategy of delivering metabolites downstream of the inhibitory node. Overall, it is believed that advanced drug delivery strategies will play an important role in marrying the fields of immunometabolism and immunotherapy to generate translatable anti-cancer treatments.
ContributorsInamdar, Sahil (Author) / Acharya, Abhinav P (Thesis advisor) / Rege, Kaushal (Committee member) / Green, Matthew (Committee member) / Curtis, Marion (Committee member) / Seetharam, Mahesh (Committee member) / Arizona State University (Publisher)
Created2022
Description
This work aims to characterize protein-nanoparticle interactions through the application of experimental techniques to aid in controlled nanoparticle production for various applications from manufacturing through medical to defense. It includes multiple steps to obtain purified and characterized protein and then the production of nanoparticles using the protein. This application of protein requires extremely pure homogenous solution of the protein that was achieved using numerous protein separation techniques which were experimented with. Crystallization conditions, protein separation methods and protein characterization methods were all investigated along with the protein-nanoparticle interaction studies. The main protein of study here is GroEL and the inorganic nanoparticle used is platinum. Some studies on MBP producing gold nanoparticles from an ionic gold precursor were also conducted to get a better perspective on nanoparticle formation. Protein purification methods, crystallization conditions, Car-9 tag testing and protein characterization methods were all investigated along with the focus of this work. It was concluded that more Car9 studies need to be carried out before being used as in the form of a loop in the protein. The nanoparticle experiments were successful and platinum nanoparticles were successfully synthesized using GroEL. The direction of further research in protein-nanoparticle studies are outlined towards the end of the thesis.
ContributorsSirajudeen, Luqmanal Hakim (Author) / Nannenga, Brent L. (Thesis advisor) / Acharya, Abhinav P (Committee member) / Mills, Jeremy H (Committee member) / Arizona State University (Publisher)
Created2019