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