Ultrasmall
gold nanoclusters (AuNCs) are emerging as promising
luminescent nanoprobes for bioimaging due to their fantastic photoluminescence
(PL) and renal-clearable ability. However, it remains a great challenge
to design them for in vivo sensitive molecular imaging in desired
tissues. Herein, we have developed a strategy to tailor the PL and
biofate of near-infrared II (NIR-II)-emitting AuNCs via ligand anchoring
for improved bioimaging. By optimizing the ligand types in AuNCs and
using Er3+-doped lanthanide (Ln) nanoparticles as models,
core–satellite Ln@AuNCs assemblies were rationally constructed,
which enabled 2.5-fold PL enhancement of AuNCs at 1100 nm and prolonged
blood circulation compared to AuNCs. Significantly, Ln@AuNCs with
dual intense NIR-II PL (from AuNCs and Er3+) can effectively
accumulate in the liver for ratiometric NIR-II imaging of H2S, facilitated by H2S-mediated selective PL quenching
of AuNCs. We have then demonstrated the real-time imaging evaluation
of liver delivery efficacy and dynamics of two H2S prodrugs.
This shows a paradigm to visualize liver H2S delivery and
its prodrug screening in vivo. Note that Ln@AuNCs are body-clearable
via the hepatobiliary excretion pathway, thus reducing potential long-term
toxicity. Such findings may propel the engineering of AuNC nanoprobes
for advancing in vivo bioimaging analysis.