Self-Assembly of Luminescent Gold Nanoparticles with Sensitive pH-Stimulated Structure Transformation and Emission Response toward Lysosome Escape and Intracellular Imaging.

Ultrasmall luminescent gold nanoparticles (AuNPs, d < 3.0 nm) with distinct optical properties and good biocompatibilities hold enormous promise for advanced disease theranostics. However, ultrasmall AuNPs generally show low cellular interaction and are hardly ever transported into the specific subcellular compartments, hampering their further biomedical use in cellular delivery and intracellular tracking. Using a conventional cationic polymer chitosan (CS) with the isoelectric point of 6.5 as a template, ultrasmall luminescent AuNPs can be easily formed into self-assembled nanostructures (AuNPs@CS) with significantly enhanced cellular interaction capability and sensitive emission response toward subcellular location. The self-assembled AuNPs@CS become compacted nanostructures (∼23.5 nm) with high luminescence at low pH values (e.g., pH < 6.5) but reversibly transform to swelled structures with weak luminescence at high pH values (e.g., pH 7.4). The self-assembly of AuNPs not only improves the emission properties but also alters the surface charge and assembly size, resulting in both enhanced cellular internalization and effective endosomal escape capability. More importantly, the sensitive luminescence response of the AuNPs@CS from the acidic organelle lysosome to the neutral cytoplasm demonstrates the great potential in optical intracellular tracking.