Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), a subtype of breast cancer that is aggressive with poor prognosis. While chemotherapeutics are potent, these agents suffer from a lack of specificity and are equally toxic to cancer and nonmalignant cells and tissues. Targeted therapies for TNBC treatment are not available at this point, largely due to the absence of well-established clinical molecular targets. In recent years, several cell surface receptors on TNBC cells have been identified that are being targeted using engineered antibodies and tumor homing/targeting peptides for site-specific delivery of chemotherapeutics. We engineered TNBC cell targeting peptides, such as linear and cyclic <b>18-4</b>, that specifically bind cell surface receptor keratin 1 (K1) on TNBC cells. We used different chemistries to link the targeting peptide to cytotoxic doxorubicin (payload) to form peptide-drug conjugates (PDCs). In this talk, conjugate syntheses with different linker chemistries, high specific uptake and toxicity of PDCs toward TNBC cells compared to free doxorubicin, and mechanism of PDC uptake by breast cancer cells will be presented. The implications of the peptide, linker and the cytotoxic payload for improved efficacy in TNBC treatment will be discussed.

Peptide-drug conjugates for improved efficacy of chemotherapy for treatment of triple-negative breast cancer

ACS Spring Meeting 2021

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