dc.contributor.author	Cornell, Hannah D.	en
dc.contributor.committeechair	Morris, Amanda	en
dc.contributor.committeemember	Tanko, James M.	en
dc.contributor.committeemember	Gandour, Richard D.	en
dc.contributor.committeemember	Matson, John	en
dc.contributor.department	Chemistry	en
dc.date.accessioned	2022-05-21T08:00:25Z	en
dc.date.available	2022-05-21T08:00:25Z	en
dc.date.issued	2022-05-20	en
dc.description.abstract	The development of controllable drug delivery systems is crucial for reducing toxicity and minimizing off-target drug effects for patients undergoing chemotherapy. Metal–organic frameworks (MOFs) are a class of hybrid materials that have become of interest in the field of drug delivery. MOFs are composed of metal nodes and organic bridging ligands. MOFs have a wide range of desirable properties including chemical stability, high porosity, and structural tunability which have positioned them as successful drug carriers. Through judicious choice of linker, stimuli-responsive MOFs can be synthesized to achieve precise control over cargo release. Previously, our lab developed a novel light-responsive drug delivery system using a framework known as UiO-AZB (UiO= University of Oslo, AZB=4,4ʹ-azobenzenedicarboxylic acid). This MOF contains a photoswitchable azobenzene linker. Upon irradiation with ultraviolet light, the compound undergoes a structural change known as photoisomerization, resulting in degradation of the MOF structure and simultaneous release of encapsulated cargo. To improve the clinical relevance of our framework, we focus on developing synthetic methods for production of visible light-responsive azobenzene photoswitches. A green light-responsive MOF (UiO-AZB-F) containing a 4,4ʹ-(diazene-1,2- diyl)bis(3,5-difluorobenzoic acid) linker was developed as a drug delivery system for the treatment of colorectal cancer. Our work also focuses on optimizing various aspects of MOF design to maximize and diversify cargo loading and precisely control cargo release rates. A combined computational and experimental investigation of drug adsorption process reveals that the presence of solvent can significantly impact the adsorption of drug molecules within MOF pores. To address these concerns, a variety of drug loading procedures were screened to determine conditions for maximizing the loading of diverse drug cargoes. Conditions for the loading of single agents as well as chemotherapy cocktails were explored to expand the application of our delivery platform to other cancer types including lung, pancreatic, bladder and cervical. To modulate the release of cargo, a series of MOFs containing precise ratios of green light-responsive linker were synthesized to create a platform for sustained release. Remarkably, several MOF derivatives showed enhancement in drug adsorption, highlighting the important role of host–guest interactions in nanocarrier development. Holistically, this work highlights the promise of stimuli-responsive MOFs as drug delivery platforms.	en
dc.description.abstractgeneral	Cancer is one of the leading causes of death worldwide. In 2021, nearly 2 million people in the U.S. were diagnosed with cancer. For patients undergoing chemotherapy treatment, the side effects of potent chemotherapeutics are often debilitating. Drug- delivery systems serve as a promising platform for localizing the delivery of chemotherapeutic drugs within a diseased area. When chemotherapeutics are delivered precisely to tumor regions via drug delivery systems, systemic side effects are significantly diminished. In this work, a series of materials known as metal–organic frameworks (MOFs) are developed as carriers for chemotherapeutic cargo. Due to the incorporation of photoactivated compounds within the backbone, these MOFs can be degraded on-demand through green light irradiation. As the framework degrades into small molecule components, drug cargo is simultaneously released. Methods for maximizing MOF drug loadings, diversifying the types of cargo that can be incorporated, and modifying cargo release rates are also investigated. This work establishes stimuli-responsive MOFs as promising materials for on-demand drug delivery.	en
dc.description.degree	Doctor of Philosophy	en
dc.format.medium	ETD	en
dc.identifier.other	vt_gsexam:34847	en
dc.identifier.uri	http://hdl.handle.net/10919/110127	en
dc.language.iso	en	en
dc.publisher	Virginia Tech	en
dc.rights	In Copyright	en
dc.rights.uri	http://rightsstatements.org/vocab/InC/1.0/	en
dc.subject	metal–organic framework	en
dc.subject	drug delivery	en
dc.subject	stimuli-responsive	en
dc.subject	azobenzene	en
dc.title	A Green Light at the Intersection of Metal-Organic Frameworks and Drug Delivery	en
dc.type	Dissertation	en
thesis.degree.discipline	Chemistry	en
thesis.degree.grantor	Virginia Polytechnic Institute and State University	en
thesis.degree.level	doctoral	en
thesis.degree.name	Doctor of Philosophy	en

A Green Light at the Intersection of Metal-Organic Frameworks and Drug Delivery

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