Journal
JOURNAL OF MOLECULAR RECOGNITION
Volume 16, Issue 5, Pages 280-287Publisher
WILEY
DOI: 10.1002/jmr.638
Keywords
cancer therapy; drug delivery; human calcitonin; carrier peptides; endocytosis
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Severe and often therapy-limiting side effects are a major obstacle in cancer chemotherapy. New delivery concepts reducing systemic side effects are needed in order to optimize anticancer therapies. Several approaches have been followed, most of them concentrating on macromolecular carriers like liposomes, monoclonal antibodies, serum proteins or polyethylene glycol. We present here a novel type of anthracycline conjugate, using a small carrier peptide derived from the peptide hormone human calcitonin (hCT). The carrier peptide hCT(9-32) has so far been shown to be capable of transporting fluorophores or proteins across cellular membranes. Two different carrier peptide-daunorubicin conjugates were prepared, one with an acid-stable amide bond, the second with an acid-labile hydrazone bond. In vitro studies with daunorubicin linked to the carrier peptide via an acid-labile hydrazone bond demonstrated comparable cytotoxicity to daunorubicin in various daunorubicin sensitive cell lines (neuroblastoma cell lines SK-N-MC and SMS-KAN; HEK 293 T cells). In addition, fluorescence microscopy provided further insight into the mechanism of uptake of the carrier peptide hCT(9-32), indicating that endosomal compartments with reduced pH are involved in the intracellular release of daunorubicin. Copyright (C) 2003 John Wiley Sons, Ltd.
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