Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells

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• 作者：Artjom Wischnjow ; Dikran Sarko ; Maria Janzer ; Christina Kaufman ; Barbro Beijer ; Sebastian Brings ; Uwe Haberkorn ; Gregor Larbig ; Armin Kübelbeck ; Walter Mier
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：April 20, 2016
• 年：2016
• 卷：27
• 期：4
• 页码：1050-1057
• 全文大小：537K
• 年卷期：0
• ISSN：1520-4812

文摘

Kidney-specific drug targeting is an attractive strategy to reduce unwanted side effects and to enhance drug efficacy within the renal tissue. For this purpose a novel kidney-specific drug carrier was developed. The peptide sequence (KKEEE)₃K triggers exceptional renal specificity at high accumulation rates. Micro-PET imaging studies of megalin-deficient mice indicate that the cellular endocytosis of this carrier is mediated by megalin. This assumption is supported by immunohistochemical analysis of FITC-labeled carrier peptide, which exclusively accumulated at the apical side of proximal tubule cells within the renal cortex. Scintigraphic studies of modified ciprofloxacin conjugated to (KKEEE)₃K confirmed the excellent drug targeting potential of the peptide carrier. The conjugate accumulated entirely in the kidneys, revealing flawless redirection of ciprofloxacin, a compound that is mainly excreted by the liver. In conclusion, these results suggest the potential of (KKEEE)₃K as a promising candidate for kidney-targeted drug delivery to proximal tubule cells.