Isolation of a peptide for targeted drug delivery into human head and neck solid tumors

Cancer Res. 2000 Dec 1;60(23):6551-6.

Abstract

Lack of tumor specificity remains a major problem with chemotherapies in that side effects prevent the delivery of dosages of drugs that are required to eliminate tumors. In this report, we describe the isolation of a 12-mer peptide (HN-1), with approximately 1% of the mass of typical antibodies, that meets several criteria for targeted drug delivery into a solid tumor. First, internalization of HN-1 by human head and neck squamous cell cancer (HNSCC) cells suggests that HN-1 is capable of translocating drugs across cell membranes. Second, HN-1 appears to be HNSCC-specific, given its reduced uptake by nonmalignant human oral keratinocytes and other types of human cells, its preferential binding to primary HNSCC, and its localization to HNSCC-derived xenografts. Third, the presence of HN-1 within HNSCC xenografts suggests that it is capable of penetrating tumor tissues. Our results establish the utility of tumor-specific peptides for targeted drug delivery into solid tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Astrocytoma / drug therapy
  • Astrocytoma / metabolism
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Membrane / metabolism
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Contrast Media / administration & dosage
  • Contrast Media / pharmacokinetics
  • Drug Carriers
  • Drug Delivery Systems*
  • Female
  • Fluorescein / administration & dosage
  • Fluorescein / pharmacokinetics
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Oligopeptides / administration & dosage
  • Oligopeptides / isolation & purification*
  • Oligopeptides / pharmacokinetics*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media
  • Drug Carriers
  • HN-1 peptide
  • Oligopeptides
  • Fluorescein