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ENGINEERING SELF-ASSEMBLING BIOMATERIALS USING PROTEIN BLOCK COPOLYMERS FOR DRUG DELIVERY AND MOLECULAR IMAGING IN GLIOBLASTOMA
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Montclare, Jin Kim
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Fall 2023
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2023-08-23
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Bhattacharya_thesis.pdf
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ABSTRACT
ENGINEERING SELF-ASSEMBLING BIOMATERIALS USING PROTEIN BLOCK COPOLYMERS FOR
DRUG DELIVERY AND MOLECULAR IMAGING IN GLIOBLASTOMA
By
Aparajita Bhattacharya
Thesis Advisor: Jin Kim Montclare, PhD
A thesis submitted to the faculty of The School of Graduate Studies
State University of New York Downstate Health Sciences University in partial fulfillment of
the requirements for the Degree of Doctor of Philosophy in Molecular and Cellular Biology
Aug 22, 2023
In this thesis, we discuss the engineering a single protein-based system combining drug
delivery and diagnostic capabilities in addition to its variants. Chapter 2 covers the
engineering and characterization of a protein-based theranostic nanomaterial, TRAP2 that
performs drug delivery and near infrared fluorescence imaging in a preclinical model of
glioblastoma. Though NIR imaging has limited application in the clinical setting except its
role in surgical guidance, it has vast potential within preclinical research due to its tissue
penetration. To enhance the targeting ability of TRAP2 to glioblastoma, Chapter 3 explores
the recombinant conjugation of a transferrin receptor-targeting short peptide tag to the
protein and its characterization. Chapter 4 addresses the development of protein engineered
PET agent, 18F-TRAP3, for bestowing it with a high LOD and resulting sensitivity. We employ
residue-specific incorporation of an azide-bearing methionine analog, azidohomoalanine to
give rise to clickable azide-functionalized TRAP3AHA that can be subsequently conjugated to
a 18F bearing alkyne analog of boron-dipyrromethene (BDP FL DBCO) dye, imparting it an
ability to be used as a dual modality PET probe capable of fluorescence as well as 18F-PET
imaging. Together, these proteins represent an endeavor directed at the development of
theranostic agents for enhanced drug delivery and preclinical imaging in glioblastoma.
Citation
Bhattacharya, A (2023). ENGINEERING SELF-ASSEMBLING BIOMATERIALS USING PROTEIN BLOCK COPOLYMERS FOR DRUG DELIVERY AND MOLECULAR IMAGING IN GLIOBLASTOMA. [Doctoral dissertation, SUNY Downstate Health Sciences University]. SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/14755