title: Delivery of substances and their target-specific topical activation.
abstract: Goal in pharmaceutical research is achievement of necessary drug concentrations in the target organ, effective treatment with safe delivery of genetic agents, while sparing normal tissue and minimizing side effects. A new "BioShuttle"-delivery system harbouring a cathepsin B cutting site, a nuclear address sequence and a functional peptide was developed and tumor cells were treated. Transport and subcellular activation were determined by confocal laser scanning microscopy permitting the conclusion: BioShuttle-conjugates prove as efficient tools for genetic interventions by selective and topical activation of therapeutic peptide precursors by enzymatic cleavage. As shown here for glioma cells and the cathepsin B cleavable site, living cells can be treated with high specificity and selectivity for diagnostic and therapeutic purposes.
authors.affiliation: Peptide Synthesis Facility, German Cancer Research Center, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. r.pipkorn@dkfz.de
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Pipkorn
authors.forename: Waldemar
authors.initials: W
authors.lastname: Waldeck
authors.forename: Herbert
authors.initials: H
authors.lastname: Spring
authors.forename: Jürgen W
authors.initials: JW
authors.lastname: Jenne
authors.forename: Klaus
authors.initials: K
authors.lastname: Braun
mesh_terms: D000287:Administration, Topical; D000595:Amino Acid Sequence; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D006801:Humans; D018613:Microscopy, Confocal; D012680:Sensitivity and Specificity
chemical_list: D002401:Cathepsin B