Peptide-Drug Conjugate Targeting Keratin 1 Inhibits Triple-Negative Breast Cancer in Mice.

Selective delivery of chemotherapy to the tumor site while sparing healthy cells and tissues is an attractive approach for cancer treatment. Carriers such as peptides can facilitate selective tumor targeting and payload delivery. Peptides with specific affinity for the overexpressed cell-surface receptors in cancer cells are conjugated to chemotherapy to afford peptide-drug conjugates (PDCs) that show selective uptake by cancer cells.

Targeting Triple Negative Breast Cancer Cells with Novel Cytotoxic Peptide-Doxorubicin Conjugates.

In this study, we have designed and synthesized two novel peptide-drug conjugates (PDCs) where the drug, doxorubicin (Dox), is linked to the peptide via a succinimidyl thioether bond or a hydrazone linker. A highly specific and proteolytically stable breast cancer cell targeting peptide (WxEAAYQrFL) is conjugated to Dox to synthesize peptide-Dox thioether () or hydrazone () conjugate. The evaluation of the stability in water, media, and human serum showed that the conjugate with the succinimidyl thioether linkage is more stable compared to the acid-sensitive hydrazone containing conjugate .