Delivery of substances and their target-specific topical activation.
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.
Pipkorn
Rüdiger
R
Peptide Synthesis Facility, German Cancer Research Center, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. r.pipkorn@dkfz.de
Waldeck
Waldemar
W
Spring
Herbert
H
Jenne
Jürgen W
JW
Braun
Klaus
K
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
D002401:Cathepsin B