Abstract

Breast cancer (BrCa) is the second most common cancer and the second leading cause of cancer death among women in the U.S. This highlights the necessity of developing effective therapeutic agents to aid in the treatment of BrCa. A promising new method of treatment is photodynamic therapy (PDT), a clinically approved therapeutic procedure that uses a porphyrin-based photosensitizer (PS) dye to kill cancer cells upon excitation with a light source. It has been observed that chelation of a metal ion into the porphyrin increases the therapeutic efficacy. We have developed a synthetic route incorporating the palladized analogue of the PS dye meso-Pyropheophorbide a (mPPa) for use as a targeted therapeutic agent for the treatment of breast cancer. Our hope is to create a non-invasive treatment option that can be used as a stand-alone treatment for small surface level tumors or as part of lumpectomy operations to kill residual cancer cells left in the margins of surgery. A disadvantage of the porphyrin rings is that they are insoluble in water. To address that issue, a previous graduate student of our lab developed a “water-solubilizing” (WS) module that contains several sulfonate groups that impart water solubility. This is attached to a peptide module that is comprised of the PS dye attached to the side chain of a lysine. The module may then be attached further to a targeting group. To improve selectivity, we attached a linear and cyclic decapeptide, 18-4 and c(18-4) which have specificity for binding to receptors on the surface of breast cancer cells, including the most lethal triple negative type (TN-BrCa). We have explored 3 different pathways and successfully synthesized and purified the penultimate puzzle piece molecule for PDT that contains a water-soluble, metal-chelated porphyrin photosensitizer module on a lysine. This compound is being carried on by members of our group with respect to coupling to c(18-4).

Library of Congress Subject Headings

Molecular probes--Diagnostic use; Breast--Cancer--Diagnosis; Breast--Cancer--Treatment; Photochemotherapy

Publication Date

8-2025

Document Type

Thesis

Student Type

Graduate

Degree Name

Chemistry (MS)

Department, Program, or Center

Chemistry and Materials Science, School of

College

College of Science

Advisor

Hans Schmitthenner

Advisor/Committee Member

Lea Michel

Advisor/Committee Member

Douglas Tusch

Campus

RIT – Main Campus

Plan Codes

CHEM-MS

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