CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, China.
Biomaterials. 2010 Oct;31(30):7606-19. doi: 10.1016/j.biomaterials.2010.06.051. Epub 2010 Jul 24.
Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents.
金纳米棒（AuNRs）已被认为是用于生物医学应用的有前途的材料，例如传感、成像、基因和药物输送和治疗，但它们的毒理学问题仍存在争议，特别是对于用种子介导法合成的 AuNRs。在这项研究中，我们研究了纵横比和表面涂层对其毒性和细胞摄取的影响。细胞摄取高度依赖于纵横比和表面涂层。然而，表面化学起主要作用，因为 PDDAC 涂层的 AuNRs 表现出更强的被细胞内化的能力。目前的数据表明，形状无关但涂层依赖的细胞毒性。在悬浮溶液中以及 AuNRs 表面留下的 CTAB 分子被确定为细胞毒性的实际原因。CTAB 可以在没有 AuNRs 的情况下进入细胞，损伤线粒体，然后诱导细胞凋亡。还使用具有不同涂层的 AuNRs 研究了表面涂层对毒性和细胞摄取的影响。当 AuNRs 被添加到培养基中时，蛋白质会迅速吸附在 AuNRs 上，使表面带负电荷。表面电荷可能不会直接影响细胞摄取。我们进一步证明，吸附在 AuNRs 上的血清蛋白（尤其是 BSA）的量与 AuNRs 进入细胞的能力呈正相关。此外，我们已经成功地揭示了具有 4 的纵横比的带正电荷的 PDDAC 涂层的 AuNRs 具有低毒性和高细胞摄取效率的理想组合，有望成为光热治疗剂。
