p Electrostatically Controlled ex Situ and in Situ Polymerization of Diacetylene-Containing Peptide Amphiphiles in Living Cells

Precise control of diacetylene-containing peptide amphiphile (DPA) based supramolecular architectures is important for their in cellulo polymerization behaviors and biomedical applications. Herein, we reported two DPAs (cationic PA-NH2 and zwitterionic PA-OH) with a similar molecular structure, which exhibited completely opposite polymerization behaviors in aqueous solution and living cells. Specifically, PA-NH2 was unpolymerizable in aqueous solution but underwent in cellulo polymerization to respond to the intracellular microenvironment. On the contrary, zwitterionic PA-OH was polymerized in solution, rather than inside living cells. Based on the results of cell viability and total internal reflection fluorescent microscopy measurement, PA-OH exhibited higher aflinity with cell membranes and lower cytotoxicity than those of PA-NH2. Therefore, it is suggested that the in cellulo polymerization of PA-NH2 should be responsive for greater cytotoxicity, rather than the membrane aflinity. This study provides an in-depth understanding of the role of charge properties in the polymerization behavior of DPAs and seeks their potential biomedical applications.