Integrin-Targeting Knottin Peptide-Drug Conjugates Are Potent Inhibitors of Tumor Cell Proliferation.

Journal Article (Journal Article)

Antibody-drug conjugates (ADCs) offer increased efficacy and reduced toxicity compared to systemic chemotherapy. Less attention has been paid to peptide-drug delivery, which has the potential for increased tumor penetration and facile synthesis. We report a knottin peptide-drug conjugate (KDC) and demonstrate that it can selectively deliver gemcitabine to malignant cells expressing tumor-associated integrins. This KDC binds to tumor cells with low-nanomolar affinity, is internalized by an integrin-mediated process, releases its payload intracellularly, and is a highly potent inhibitor of brain, breast, ovarian, and pancreatic cancer cell lines. Notably, these features enable this KDC to bypass a gemcitabine-resistance mechanism found in pancreatic cancer cells. This work expands the therapeutic relevance of knottin peptides to include targeted drug delivery, and further motivates efforts to expand the drug-conjugate toolkit to include non-antibody protein scaffolds.

Full Text

Duke Authors

Cited Authors

  • Cox, N; Kintzing, JR; Smith, M; Grant, GA; Cochran, JR

Published Date

  • August 16, 2016

Published In

Volume / Issue

  • 55 / 34

Start / End Page

  • 9894 - 9897

PubMed ID

  • 27304709

Pubmed Central ID

  • PMC6231717

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

Digital Object Identifier (DOI)

  • 10.1002/anie.201603488


  • eng

Conference Location

  • Germany