华南理工大学刘锦斌团队报道了发光金纳米颗粒肾内PH响应性自组装诊断早期肾损伤。相关研究成果发表在2024年5月4日出版的《德国应用化学》。

代谢性酸中毒诱导的肾损伤（MAKI）在早期无症状且缺乏临床生物标志物，但会迅速发展为严重的肾纤维化，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非延迟生物标志物的快速和无创策略，对于及时进行肾脏保护性干预至关重要。

该文中，研究人员在第二次近红外发射中开发了pH响应性发光金纳米颗粒（p-AuNPs），该纳米颗粒与2，3-二甲酸酐偶联的β-巯基乙胺和阳离子2-二乙氨基乙硫醇盐酸盐共包被，显示出敏感的pH诱导电荷逆转和肾内自组装，可对不同阶段的MAKI进行高灵敏度和长时间（~24h）成像。通过整合pH诱导的肾内自组装，和pH触发的带正电荷的p-AuNPs与肾小管细胞之间增强的相互作用的优势，早期和晚期MAKI可以在注射后10分钟内快速分化（p.i.），对比度指数（CI）分别为3.5和4.3。相应的最大CI在12 h p.i.时分别达到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逐渐恢复，并表现出卓越的药物筛选能力。这种pH反应策略显示出对肾功能障碍进展的反馈的巨大前景，为pH相关疾病的早期诊断开辟了新的可能性。

附：英文原文

Title: Intrarenal pH-Responsive Self-Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury

Author: Zhipeng Zhao, Kui He, Ben Liu, Wenyan Nie, Xiaoxi Luo, Jinbin Liu

Issue&Volume: 2024-05-04

Abstract: 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.

DOI: 10.1002/anie.202406016

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202406016