Tailoring Oxidation Responsiveness of Gold Nanoclusters via Ligand Engineering for Imaging Acute Kidney Injury

Gold nanoclusters (AuNCs) have shown great promise for in vivo imaging because of their definable structure, tunable photoluminescence (PL), and desired renal clearance. However, current understanding of the responsiveness of AuNCs to biological substances is still limited, which may hamper their biomedical applications. Herein, we explore the oxidation responsiveness of near-infrared II (NIR-II) luminescent AuNCs capped with two different ligands, which can be optimized for high-efficiency NIR-II PL imaging of mice acute kidney injury (AKI) featuring high-level peroxynitrite anions (ONOO-). We found that in the presence of ONOO-, N-acetylcysteine-capped AuNCs (NAC-AuNCs) tended to be oxidized more easily than that capped with the macromolecular mercapto-beta-cyclodextrin (CDS-AuNCs), resulting in the aggregation of NAC-AuNCs into large-sized assemblies, which was not observed in CDS-AuNCs. The oxidation-triggered morphology, composition, and NIR-II PL changes in NAC-AuNCs were then systematically studied. We finally demonstrated that NAC-AuNCs can be implemented for sensitive NIR-II PL imaging of mice AKI, facilitated by the synergetic in situ AuNC aggregation and decreased glomerular filtration rate (GFR) in the injured kidney, which outperforms the methods solely based on the decreased GFR effect. Therefore, this work highlights the critical significance of ligand engineering in AuNCs and may motivate future design of AuNCs for diverse bioimaging applications.