Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin 300350, China.
Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Bioconjug Chem. 2024 Apr 17;35(4):540-550. doi: 10.1021/acs.bioconjchem.4c00113. Epub 2024 Apr 1.
Ultrasmall Au(MPA) clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au(MPA) and AuZn(MPA) can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.
由于具有明确可调的结构和性质，超小的 Au(MPA) 团簇在生物催化剂和生物成像方面具有巨大的潜力。因此，Au 纳米团簇 (Au NCs) 的药代动力学和毒性对于临床转化非常重要，尤其是在高剂量下。在此，研究了暴露于 Au NCs（300 和 500 mg/kg）后的血液、组织和神经影响，其中浓度是治疗用途的 10 倍。即使在超高剂量 500 mg/kg 下，注射的 Au NCs 的生化和血液参数仍在正常范围内。同时，Au NC 组未观察到组织病理学变化，免疫荧光染色显示主要器官无明显病变。此外，实时近红外-II (NIR-II) 成像显示，大多数 Au(MPA) 和 AuZn(MPA) 可以通过肾脏代谢。这些结果通过评估超高剂量下主要器官毒性作用的表现，证明了 Au NCs 具有良好的生物安全性，为它们在生物医学中的应用提供了可靠的数据。
