Wang Ximeng, Yue Zhengya, Zhong Wencheng, Wang Lin, Shang Li
State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University (NPU), Xi'an 710072, China.
ACS Appl Mater Interfaces. 2025 Jan 22;17(3):4689-4698. doi: 10.1021/acsami.4c20389. Epub 2025 Jan 7.
Gold nanoclusters (AuNCs) have garnered significant attention in biomedical applications, particularly in biosensing, cancer therapy, and imaging, due to their unique optical property, good biocompatibility, and distinct bioactivity. Understanding the cellular uptake behavior of AuNCs is critical to improve the efficacy of their applications, whose mechanism has not been adequately validated. In this work, we synthesized AuNCs with varying surface modifications to quantify the exact law of surface charge on the cellular uptake of AuNCs in a multidimensional manner by using 3D multicellular tumor spheroids of both HeLa cells and MCF-7 cells as the model system. By the combined use of fluorescence live cell imaging and inductively coupled plasma-mass spectrometry, we systematically investigated the effect of surface charge on their uptake rate, intracellular versus intercellular distribution, and penetration depth in a quantitative manner. Our results showed that the cellular uptake of AuNCs was strongly charge dependent, with uptake efficiency increasing with the degree of surface positive charges. A similar charge-dependent uptake behavior was observed in both 2D cell cultures and 3D multicellular tumor spheroids, but the difference in 3D spheroids was less pronounced, in comparison to the 2D model. The effect of AuNCs' surface charge on the cellular uptake has been quantified in multiple dimensions in this work, which also provides crucial knowledge for effective cancer therapeutics and imaging applications based on AuNCs and other nanomaterials.
金纳米团簇（AuNCs）因其独特的光学性质、良好的生物相容性和显著的生物活性，在生物医学应用中备受关注，尤其是在生物传感、癌症治疗和成像方面。了解AuNCs的细胞摄取行为对于提高其应用效果至关重要，但其机制尚未得到充分验证。在这项工作中，我们合成了具有不同表面修饰的AuNCs，以HeLa细胞和MCF-7细胞的3D多细胞肿瘤球体为模型系统，通过多维度方式量化表面电荷对AuNCs细胞摄取的确切规律。通过结合荧光活细胞成像和电感耦合等离子体质谱，我们系统地定量研究了表面电荷对其摄取速率、细胞内与细胞间分布以及穿透深度的影响。我们的结果表明，AuNCs的细胞摄取强烈依赖于电荷，摄取效率随表面正电荷程度的增加而提高。在二维细胞培养和三维多细胞肿瘤球体中均观察到类似的电荷依赖性摄取行为，但与二维模型相比，三维球体中的差异不太明显。这项工作在多个维度上量化了AuNCs表面电荷对细胞摄取的影响，这也为基于AuNCs和其他纳米材料的有效癌症治疗和成像应用提供了关键知识。
