Isolation of a peptide for targeted drug delivery into human head and neck solid tumors.
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.
Hong
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The Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Clayman
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D000595:Amino Acid Sequence; D000818:Animals; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D003287:Contrast Media; D004337:Drug Carriers; C417565:HN-1 peptide; D009842:Oligopeptides; D019793:Fluorescein