ENGINEERING SELF-ASSEMBLING BIOMATERIALS USING PROTEIN BLOCK COPOLYMERS FOR DRUG DELIVERY AND MOLECULAR IMAGING IN GLIOBLASTOMA

Abstract

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.