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Author ORCID Identifier
Open Access Dissertation
Doctor of Philosophy (PhD)
Year Degree Awarded
Month Degree Awarded
Vincent M. Rotello
Michael J. Maroney
Lisa M. Minter
Animal Sciences | Bacteriology | Biology and Biomimetic Materials | Catalysis and Reaction Engineering | Nanomedicine | Nanoscience and Nanotechnology | Organic Chemicals | Other Materials Science and Engineering | Other Microbiology
Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for bioorthogonal imaging and therapeutic applications.
My research is focused on modulating nanozyme surface chemistry for controlled localization of nanozymes at the site of interest for controlled bioorthogonal catalysis in mammalian and bacterial cells. In the intial studies, I have demonstrated controlled localization of nanozymes inside and outside the mammalian cell membrane. Nanozymes bearing cationic charge were used for activation of substrates inside the cells, owing to their high cellular internalization, whereas relatively impermeable zwitterionic nanozymes were used for extracellular activation of substrate molecules. Next, these cell-penetrating nanozymes were loaded inside the macrophages to develop a toolkit for targeting tumor site. With the inherent ability of macrophages to home in on tumor site, I demonstrated that nanozymes can generate chemotherapeutic drugs to selectively kill the cancer cells. This strategy has potential to reduce the off-target toxicity of the chemotherapy drugs.
In subsequent studies, I utilized engineered bioorthogonal nanozymes to target bacterial biofilm infections. Functionalization of nanozyme surface with pH-responsive ligands enabled us to selectively image bacterial biofilms by targeting the acidic microenvironment of biofilms. In another strategy, nanozymes were non-covalently adsorbed on the surface of Red Blood Cells (RBCs) for selective killing of pathogenic bacteria. RBCs being highly susceptible to bacterial exotoxins were hemolyzed, resulting in selective accumulation of nanozymes at site of infection. These nanozymes in-turn activated pro-antibiotics at the site of bacterial infection to eradicate biofilms. Overall, these studies show strong potential of engineered nanozymes toolkit to generate imaging and therapeutic agents at targeted sites utilizing bioorthogonal chemistry.
Das, Riddha, "Engineered Nanoparticles for Site-Specific Bioorthogonal Catalysis: Imaging and Therapy" (2020). Doctoral Dissertations. 1819.
Available for download on Monday, February 01, 2021
Animal Sciences Commons, Bacteriology Commons, Biology and Biomimetic Materials Commons, Catalysis and Reaction Engineering Commons, Nanomedicine Commons, Nanoscience and Nanotechnology Commons, Organic Chemicals Commons, Other Materials Science and Engineering Commons, Other Microbiology Commons