Decomposition-induced Assembly Of Pyrene-derivative Micelles Under Mild Conditions And Its Influence On Cytoviability

In recent years, self-assembly has become one of the most prominent and promising tools for preparation of various nanomaterials. In particular, assemblies with stimuli-responsive functions show promise for a variety of potential applications in biological, electronic and optoelectronic fields.Our group developed a new method for preparing one-dimensional nanotubes or nanorods from poly(allylamine hydrochloride) (PAH)-g-pyrene (Py) microcapsules. The nanotubes and nanorods were self-assembled by π-π stacking of 1-pyrenecarboxaldehyde (Py-CHO) during gradual hydrolysis of Schiff base bonds between PAH and Py-CHO in pH 0 and pH 2 solutions, respectively. However, the pH for the hydrolysis of the Schiff base bonds is too low to realize intracellular decomposition-induced assembly. Thus, the Schiff base bonds should be substituted with another type of linking bonds to enable the assembly to take place at mild intracellular conditions.For this purpose, amphiphilic pyrene-containing random copolymers with pH-sensitive hydrazone bonds were synthesized by copolymerizing hydrophobic pyrene-containing methacrylhydrazone with hydrophilic N,N-dimethylacrylamide (DMA). The hydrolysable copolymers formed spherical micelles in pH 6 water, which were further transformed into pure Py-CHO nanorods due to cleavage of the hydrazone bonds. Likewise, the shape transformation was observed under biomimetic conditions of pH 5.5 phosphate buffered saline. Moreover, the hydrolysable micelles co-cultured with A549 cells (a kind of lung cancer cells) caused higher cytotoxicity than non-hydrolysable ones without shape transformation synthesized by reducing the hydrolysable ones with NaHB4.In addition, amphiphilic pyrene-containing random copolymers with photo-sensitive pyrene ester bonds were synthesized by copolymerizing hydrophobic acrylpyrene ester with hydrophilic DMA. The photodegradable copolymers formed spherical micelles in water, which were further transformed into pure 1-pyrenemethanol (Py-CH2OH) nanorods due to cleavage of the pyrene ester bonds under 365 nm UV irradiation. Likewise, the shape transformation was observed under biomimetic conditions of artificial cytoplasm. Moreover, the group of UV irradiation after adding photodegradable micelles caused significantly higher cytotoxicity to A549 cells than the ones of only UV irradiation and only adding photodegradable micelles, respectively.