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Author ORCID Identifier
https://orcid.org/0000-0002-9585-7458
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Chemistry
Year Degree Awarded
2023
Month Degree Awarded
May
First Advisor
Vincent M. Rotello
Subject Categories
Chemicals and Drugs | Nanomedicine
Abstract
Bioorthogonal chemistry offers versatile strategies for monitoring and modulating biomolecules in their native environments through abiotic chemical reactions. Bioorthogonal catalysis via transition metal catalysts (TMCs) provides the controlled activation of anticancer therapeutics, which mimics the enzymatic amplifications. However, the direct use of TMCs in living systems faces challenges such as instability, poor solubility, and low biocompatibility. Engineering the structure of TMCs can partially solve the problems, but the rapid clearance of small molecules hurdles the in vivo applications. Therefore, embedding TMCs in/onto nanomaterials to obtain bioorthogonal nanozymes enhances stability, solubility, biocompatibility, and the presence of the catalysts in biological environments for drug activation.
In this thesis, I screened a library of surface-functionalized gold nanoparticles (AuNPs) to check their effect on immune cells. I chose the positively charged with hydrophilic headgroup one to hydrophobic TMCs. AuNPs insulate the catalyst from the deactivating environment. The surface ligands of AuNPs were further engineered to generate stimuli-responsive nanozymes by harnessing the formation and proteolysis of the protein corona. Moreover, the cationic-charged nanozyme exhibited prolonged stability both in vitro and in vivo, allowing for localized drug activation. The localized cancer therapy mediated by nanozymes efficiently reduced the growth of aggressive breast cancer and avoided acute liver damage, a common off-target effect of chemotherapy. The nanozymes were also applied for anticancer immunotherapy by polarizing macrophages to anticancer phenotype through activating the precursor of an immune modulator.
Other than gold nanoparticles, I functionalized zinc sulfite nanoparticles as the scaffold to integrate degradability and enhanced catalysis for anticancer drug activation. I also developed a scalable polymeric-based nanozyme that resisted serum poisoning for cancer killing. Overall, this dissertation presents the promising potential of fabricating bioorthogonal nanozymes for localized anticancer therapy.
DOI
https://doi.org/10.7275/34537381
Recommended Citation
Zhang, Xianzhi, "TRANSITION METAL CATALYST (TMC)-EMBEDDED BIOORTHOGONAL NANOZYMES FOR ANTICANCER THERAPEUTICS" (2023). Doctoral Dissertations. 2878.
https://doi.org/10.7275/34537381
https://scholarworks.umass.edu/dissertations_2/2878