Abstract

Breast cancer (BrCa) is a pressing health concern, necessitating the development of effective imaging and therapeutic agents. To address this need, we designed and synthesized molecularly targeted imaging and therapeutic agents that combine visualization and treatment of tumors in real-time. Our approach involved the development of dual-modal agents, incorporating the fluorescent near infrared (NIR) dye, IRDye78, and a chlorin-based photosensitizer (PS) dye, Mesopyropheoborbide-a (mPPa), coupled to a BrCa-targeting peptide, "18-4." Additionally, we created a water-soluble, single-modal targeted PS probe for photodynamic therapy (PDT) of BrCa for use guided by other imaging methods. Our methodology was based on a modular approach, wherein modules containing the dyes attached to a lysine scaffold were utilized to attach the dye payloads in two different combinations: one with the PS dye on the lysine side chain and fluorescent dye, IRDye78, on the n-terminus of lysine, and the other with reversed positions of the two dyes. Furthermore, we extended this method to synthesize palladium-metalated versions of these modules. For the water-soluble, targeted single-modal probe, we designed a module that incorporated the PS dye on the side chain of lysine, attached to a water-solubilizing tri-sulfonated arm on the n-terminus. This module was then coupled to the BrCa peptide, resulting in a single-modal PS for PDT of BrCa. Two probes were provided to the University of Rochester for evaluation in BrCa cells and murine models. Preliminary results confirmed the uptake of our first dual modal probe into BrCa cells through fluorescent microscopy. This work represents the first example of receptor-targeted, dual-modal imaging and therapy agents for combined imaging and PDT of BrCa. Additionally, a new approach to water-soluble, single-modal targeted PDT agent is introduced. Overall, this comprehensive approach offers hope for improved outcomes in lumpectomy and represents a substantial advancement in the fight against breast cancer.

Library of Congress Subject Headings

Molecular probes--Diagnostic use; Breast--Cancer--Imaging; Peptides--Synthesis

Publication Date

8-2023

Document Type

Thesis

Student Type

Graduate

Degree Name

Chemistry (MS)

Department, Program, or Center

School of Chemistry and Materials Science (COS)

Advisor

Hans Schmitthenner

Advisor/Committee Member

Christina Goudreau Collison

Advisor/Committee Member

Michael Heagy

Campus

RIT – Main Campus

Plan Codes

CHEM-MS

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