Tandem Molecular Self‐Assembly in Liver Cancer Cells

We herein describe the tandem molecular self‐assembly of a peptide derivative (1) that is controlled by a combination of enzymatic and chemical reactions. In phosphate‐buffered saline (PBS), compound 1 self‐assembles first into nanoparticles by phosphatase and then into nanofibers by glutathione. Liver cancer cells exhibit higher concentrations of both phosphatase and GSH than normal cells. Therefore, the tandem self‐assembly of 1 also occurs in the liver cancer cell lines HepG2 and QGY7703; compound 1 first forms nanoparticles around the cells and then forms nanofibers inside the cells. Owing to this self‐assembly mechanism, compound 1 exhibits large ratios for cellular uptake and inhibition of cell viability between liver cancer cells and normal liver cells. We envision that using both extracellular and intracellular reactions to trigger tandem molecular self‐assembly could lead to the development of supramolecular nanomaterials with improved performance in cancer diagnostics and therapy. In Gegenwart von Phosphatase bildet Verbindung 1 zuerst Nanopartikel und daraufhin in Gegenwart von Glutathion Nanofasern. Dieser Prozess funktioniert sowohl in Pufferlösung als auch in Leberkrebszellen aufgrund der erhöhten Phosphatase‐ und GSH‐Konzentration. Die Zellaufnahme und Zellviabilität dieser Verbindung unterscheiden sich deutlich für normale Zellen und Leberkrebszellen.