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.