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Author ORCID Identifier
https://orcid.org/0000-0002-9898-8955
AccessType
Campus-Only Access for Five (5) Years
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Chemical Engineering
Year Degree Awarded
2023
Month Degree Awarded
May
First Advisor
Ashish Kulkarni
Subject Categories
Biochemical and Biomolecular Engineering
Abstract
Immunotherapy has become one of the hottest fields in cancer therapy over the past two decades, inspiring effective therapies that can overcome the limitations of current chemo- and radiotherapies and impact immune cells within tumors. Conventional cancer therapies encompass a myriad of side effects, off-target toxicities, and limitations. Developments in the field of nanomedicine have pushed these limits to create safer, more effective therapies, but do not take advantage of the biological ecosystem that cancer develops. While monotherapies both in chemo- and immunotherapy have advantages, cancer is a multi-faceted problem which causes dysregulation immune cell function within the tumor microenvironment, including discouraging interactions with the immune system. Here, multifunctional nanomaterials can be utilized to elicit increased therapeutic potential. One aim of this thesis is to take advantage of immunosuppressive macrophages within the tumor microenvironment and convert them to an inflammatory state and enact tumor growth inhibition. We hypothesize that by inhibiting two key pathways within immunosuppressive macrophages using vertical pathway inhibition, macrophages can be re-educated to an inflammatory phenotype from an immunosuppressive one. Here, a supramolecular platform was developed and characterized in which two inhibitors were chemically-modified to stably incorporate themselves inside. These were then extensively tested in vitro and in vivo in order to understand their biophysical characteristics, ability to inhibit pathways and change surface expressions in macrophages, and cause tumor growth inhibition while reducing off-target effects and deposition. The other aim of this thesis is to develop chemically-modifiable platforms that can be utilized as immune cell bridges between T cells and cancer. We hypothesize that utilizing dendrons and dendrimers with varying functionalities on either end of the construct that we can utilize T cell biology to create interactions with cancer cells. Here, we developed two different dendron and dendrimer systems that can be chemically-modified to take on multiple functionalities that allow for increased T cell – cancer cell interactions. These were then characterized to have orthogonal functionalities, and tested in vitro and in vivo to understand their potential as a therapeutic method of utilizing T cells to kill cancer cells.
DOI
https://doi.org/10.7275/34060674
Recommended Citation
Brouillard, Anthony F., "Multifunctional Nanomaterials for Cancer Immunotherapy: From Supramolecules to Immune Cell Bridges" (2023). Doctoral Dissertations. 2801.
https://doi.org/10.7275/34060674
https://scholarworks.umass.edu/dissertations_2/2801