Department of Electronic Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University , Shanghai 200240, P.R. China.
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai, 200237. P.R. China.
ACS Nano. 2015 Aug 25;9(8):7913-24. doi: 10.1021/acsnano.5b01685. Epub 2015 Jul 24.
A deep understanding of the interaction of a graphene oxide (GO) sheet with cells at the molecular level may expedite its biomedical application and predict its new functions and adverse effects. Herein we inspect the interaction between micrometer-sized GO (mGO), commonly used in biomedical research, and cells at the molecular level through a variety of techniques. A major finding is that, instead of direct cellular penetration, the mGO sheets can stimulate the cellular response by interacting with the membrane protein and the membrane. Specifically, it is illustrated that even within a short exposure time the mGO sheets can induce the formation of vacuoles in the cytosolic compartment and enhance the cell permeability. The vacuolization is only observed in the cells that strongly express aquaporin (AQP1), indicating the specific interaction of the mGO with AQP1. Moreover, inhibition of the AQP1 activity prevents the formation of vacuoles, revealing that the interaction of the mGO with AQP1 occurs most probably at the vestibule of AQP1 at the extracellular side. Additionally, though the cell permeability was enhanced, it only improves the penetration of small molecules, not for macromolecules such as proteins. These findings are potentially valuable in cancer therapy because AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors, and it will also be beneficial for drug transport across barrier membranes.
深入了解氧化石墨烯（GO）片与细胞在分子水平上的相互作用，可能会加速其在生物医学中的应用，并预测其新的功能和不良反应。在此，我们通过多种技术研究了常用于生物医学研究的微米级 GO（mGO）与细胞在分子水平上的相互作用。一项主要发现是，mGO 片不是直接穿透细胞，而是通过与膜蛋白和膜相互作用来刺激细胞反应。具体来说，研究表明，即使在短时间的暴露下，mGO 片也可以诱导细胞质腔室中形成空泡，并增强细胞通透性。这种空泡化仅在强烈表达水通道蛋白（AQP1）的细胞中观察到，表明 mGO 与 AQP1 的特异性相互作用。此外，抑制 AQP1 的活性可以防止空泡的形成，表明 mGO 与 AQP1 的相互作用很可能发生在细胞外侧面 AQP1 的前庭部位。此外，尽管细胞通透性增强，但它只能改善小分子的穿透，而不能用于大分子，如蛋白质。这些发现对于癌症治疗可能具有重要价值，因为不同来源的肿瘤细胞，特别是侵袭性肿瘤，都强烈表达 AQPs，并且它也将有利于药物跨屏障膜的转运。
