Qingyuan Innovation Laboratory, 1# Xueyuan Road, Quanzhou, Fujian 362801, China.
MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China.
Anal Chem. 2023 Nov 7;95(44):16153-16159. doi: 10.1021/acs.analchem.3c02698. Epub 2023 Oct 25.
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-β-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.
金纳米团簇（AuNCs）由于其可定义的结构、可调谐的光致发光（PL）和理想的肾脏清除率，在体内成像方面显示出巨大的应用潜力。然而，目前对 AuNCs 对生物物质的响应性的理解仍然有限，这可能会阻碍它们在生物医学中的应用。在此，我们研究了两种不同配体包覆的近红外二区（NIR-II）发光 AuNCs 的氧化响应性，这可以优化其用于具有高水平过氧亚硝酸盐阴离子（ONOO）的小鼠急性肾损伤（AKI）的高效 NIR-II PL 成像。我们发现，在 ONOO 存在下，N-乙酰半胱氨酸包覆的 AuNCs（NAC-AuNCs）比大分子巯基-β-环糊精包覆的 AuNCs（CDS-AuNCs）更容易被氧化，导致 NAC-AuNCs 聚集形成较大的组装体，而 CDS-AuNCs 则没有观察到这种情况。然后，我们系统地研究了 NAC-AuNCs 的氧化触发的形态、组成和 NIR-II PL 变化。最后，我们证明了 NAC-AuNCs 可以用于敏感的 NIR-II PL 成像小鼠 AKI，这得益于协同的原位 AuNC 聚集和损伤肾脏中肾小球滤过率（GFR）的降低，这优于仅基于降低 GFR 效应的方法。因此，这项工作强调了配体工程在 AuNCs 中的关键意义，并可能激发未来对不同生物成像应用的 AuNCs 的设计。
