Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor prognosis and is difficult to treat. A diagnosis of TNBC means that the three most common types of receptors known to fuel most breast cancer growth–estrogen, progesterone, and HER2– are not present in the cancer tumors. Since the tumor cells lack necessary receptors, common treatments like hormone therapies and targeted HER2 drugs are ineffective. The use of chemotherapy in treating TNBC is an effective option instead. However, chemotherapy is not selective. A peptide-drug conjugate (PDC) targeting overexpressed epidermal growth factor receptor (EGFR) in TNBC cells was synthesized to increase the uptake of drug by TNBC cells, thereby improving the safety and efficacy of chemotherapeutic doxorubicin (Dox) in TNBC treatment. This PDC includes a novel 13-mer linear peptide that was attached to Dox through a cleavable linker. It was purified by reversed-phase HPLC and characterized by MALDI-TOF mass analysis. Its stability was studied in different conditions including aqueous-organic solvent mixture, human serum and mouse serum. The PDC was stable in aqueous-organic condition. In addition, its half-life in human serum was about 12 hours indicating that it is stable enough to reach the tumor sites for its activity. MTT assay will be used to evaluate its cytotoxicity toward TNBC cells versus non-cancerous mammary epithelial cells. Initial evaluations of this PDC suggest that EGFR targeting PDCs have the potential to improve the efficacy and reduce off-target side effects of chemotherapy.

Synthesis and evaluation of a novel peptide-doxorubicin conjugate for targeted uptake by triple-negative breast cancer cells

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.