Reversible Self-Assembly of Nanoprobes in Live Cells for Dynamic Intracellular pH Imaging

Self-assembly is a powerful tool to organize the elementary molecular units into functional nanostructures, which provide reversible stimulus-responsive systems for a variety of purposes. However, the ability to modulate the reversible self-assembly in live systems remains a great challenge owing to the chemical complexity of intracellular environments, which often damage synthetic assembled superstructures. Herein, we describe a robust reversible self-assembly system that is composed of a hydrophobic gold nanoparticle (AuNP) core and a shell of pH-responsive dye-incorporated block copolymers. The reversible assembly-disassembly processes were precisely controlled through mediating the molecular interactions between the copolymers and AuNPs. More importantly, the major endogenous biospecies such as proteins will not impair the reversible self-assembly, which was supported by free-energy calculations. The reversible pH-responsive nanostructures were employed as "smart" probes for visualizing the subtle dynamic pH changes among different intracellular compartments, facilitating the study of pH influence on biological processes.