Triple negative breast cancer (TNBC) is a subtype of breast cancer with chemotherapy as a main form of treatment. A significant challenge with chemotherapeutic drugs is their toxicity to non-cancerous (normal) cells and tissues, which limits their clinical application due to the detrimental side effects such as nausea, myelosuppression and cardiotoxicity. However, targeted delivery of chemotherapeutic agents such as doxorubicin (Dox) to TNBC cells could be accomplished by linking the drug to a targeting ligand such as a peptide that binds appropriate receptors on TNBC cells. Despite promising results with peptides as targeting ligands, incorporating peptides in targeted drug delivery for clinical applications is hindered due to their fast proteolytic degradation in vitro and in vivo. Here we have designed and synthesized a novel peptide-drug conjugate using a 11-mer peptide 18-4 (CWxEAAYQrFL) with high proteolytic stability and specificity for breast cancer cells. In addition, an established crosslinker, SMCC, which was used in an FDA approved drug conjugate, was used to link peptide to the drug (Dox). The conjugate shows good stability in aqueous conditions and human serum. The in vitro cytotoxicity of the conjugate tested on two different TNBC cell lines and normal breast cell line using MTT assay showed that the conjugate is specific to cancer cells. These results are promising for the development of an effective peptide-drug conjugate for TNBC treatment.

Peptide-doxorubicin conjugate for specific uptake by triple negative breast cancer cells

2019 Fall National Meeting

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