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Multifunctional Chemical Cross-linkers for Drug Carriers and Molecular Probes

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dc.contributor.authorWalker, Joshua Aaron
dc.contributor.chairAlabi, Christopher Akinleye
dc.contributor.committeeMemberDelisa, Matthew
dc.contributor.committeeMemberBaird, Barbara Ann
dc.date.accessioned2019-10-15T16:48:09Z
dc.date.available2020-08-29T06:00:21Z
dc.date.issued2019-08-30
dc.description.abstractBioconjugates are an indispensable tool for molecular biology as well as an established modality for biomedical imaging and drug delivery. Broadly, bioconjugation is the use of a chemical cross-linker to covalently attach non-natural reporters, chemical handles, drug cargo, or targeting ligands to biologics to augment their innate properties and functions. Many bioconjugation strategies attach a single non-natural component to the biomolecule of interest. This limits the functional complexity of the resulting bioconjugate. Incorporating multiple functionalities and/or stimuli responsive units has the potential to enable new applications of bioconjugates as molecular probes and drug carriers. Herein, we present a survey of our work towards developing multifunctional bioconjugates. We develop a new strategy for the site-specific modification of native antibodies. This strategy enables dual “click” modification of native antibodies. We also develop new synthetic methods for the synthesis of oligothioetheramides. We apply this new synthesis to study the effect of cross-linker sequence on the biophysical properties of antibody-drug conjugates. Finally, we discuss our efforts to develop molecular probes to characterize the surface of extracellular vesicles and quantify endosomal escape for siRNA therapeutics. Taken together, these works highlight the importance of chemical cross-linkers in the design of multifunctional bioconjugates for a variety of applications.
dc.identifier.doihttps://doi.org/10.7298/vzs9-0176
dc.identifier.otherWalker_cornellgrad_0058F_11591
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:11591
dc.identifier.otherbibid: 11050542
dc.identifier.urihttps://hdl.handle.net/1813/67559
dc.language.isoen_US
dc.subjectChemical engineering
dc.subjectAntibody-drug Conjugates
dc.subjectBioconjugates
dc.subjectClick Chemistry
dc.subjectSequence-defined Polymers
dc.subjectsiRNA Therapeutics
dc.subjectSite-specific Protein Modification
dc.subjectChemistry
dc.subjectBioengineering
dc.titleMultifunctional Chemical Cross-linkers for Drug Carriers and Molecular Probes
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810
thesis.degree.disciplineChemical Engineering
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh.D., Chemical Engineering

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