Metabolic acidosis‐induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end‐stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH‐responsive luminescent gold nanoparticles (p‐AuNPs) in the second near‐infrared emission co‐coated with 2,3‐dimethylaleic anhydride conjugated β‐mercaptoethylamine and cationic 2‐diethylaminoethanethiol hydrochloride, which showed sensitive pH‐induced charge reversal and intrarenal self‐assembly for highly sensitive and long‐time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH‐induced intrarenal self‐assembly and enhanced interactions between pH‐triggered positively charged p‐AuNPs and renal tubular cells, the early‐ and late‐stage MAKI could be differentiated rapidly within 10 min post‐injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p‐AuNPs were demonstrated to effectively real‐time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH‐responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early‐stage diagnosis of pH‐related diseases.

中文翻译：

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肾内 pH 响应自组装发光金纳米颗粒用于诊断早期肾损伤

代谢性酸中毒肾损伤（MAKI）早期无症状且缺乏临床生物标志物，但迅速进展为严重肾纤维化，最终导致终末期肾衰竭。因此，开发直接响应肾小管酸性微环境而不是延迟生物标志物的快速和无创策略对于及时的肾脏保护干预至关重要。在此，我们在第二次近红外发射中开发了 pH 响应发光金纳米粒子 (p-AuNPs)，该纳米粒子与 2,3-二甲基丙烯酸酐共轭的 β-巯基乙胺和阳离子 2-二乙氨基乙硫醇盐酸盐共涂层，显示出敏感的 pH 诱导电荷逆转和肾内自组装，用于 MAKI 不同阶段的高灵敏度和长时间（~24 小时）成像。通过整合pH诱导的肾内自组装的优点以及pH触发的带正电的p-AuNPs和肾小管细胞之间增强的相互作用，早期和晚期MAKI可以在注射后10分钟内快速分化（pi）对比度指数 (CI) 分别为 3.5 和 4.3。相应的最大 CI 在感染后 12 小时可分别达到 5.1 和 9.2。此外，p-AuNPs 被证明可以有效地实时监测 MAKI 小鼠治疗后肾损伤的进展恢复情况，并且还表现出出色的药物筛选能力。这种 pH 响应策略在肾功能障碍进展的反馈方面显示出巨大的前景，为 pH 相关疾病的早期诊断开辟了新的可能性。