Delivery of substances and their target-specific topical activation

• Published in: Biochimica et biophysica acta 2006-05, Vol.1758 (5), p.606-610
• Main Authors: Pipkorn, Rüdiger, Waldeck, Waldemar, Spring, Herbert, Jenne, Jürgen W., Braun, Klaus
• Format: Article
• Language: English
• Subjects: Administration, Topical; Amino Acid Sequence; Cathepsin B; Cathepsin B - metabolism; Cell Line, Tumor; Cell Membrane Permeability; Chromatography, High Pressure Liquid; Drug Delivery Systems; Drug targeting; Glioblastoma multiforme; Humans; Intracellular targeting; Microscopy, Confocal; Sensitivity and Specificity; Solid phase peptide synthesis; SPPS; Transmembrane transport
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2006.03.036

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.