Ji Ding-Kun, Zhang Yue, Zang Yi, Liu Wang, Zhang Xiongwen, Li Jia, Chen Guo-Rong, James Tony D, He Xiao-Peng
Key Laboratory for Advanced Materials & Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, P. R. China.
J Mater Chem B. 2015 Dec 21;3(47):9182-9185. doi: 10.1039/c5tb02057c. Epub 2015 Nov 11.
Intercellular glycoligand-receptor interactions are implicated in a number of disease-related processes. Effective tools that target these receptors may facilitate disease theranostics. However, owing to their low binding affinity, multivalent presentation of glycoligands is needed to increase the avidity with transmembrane receptors. While previous strategies focus on the covalent coupling of glycoligands to a synthetic backbone, we show here that the use of graphene oxide (GO) greatly enhances the cellular and tissue imaging ability of a small-molecule fluorescence glycoprobe. We determine that GO with an optimum size may serve as a clustering platform to reinforce the interaction of the glycoprobe with its selective receptor on a cancer cell. This phenomenon has been consistently observed with the xenograft tissue of a tumor-bearing mouse. Using this principle we have further constructed a supramolecular glycocomposite by co-assembling the glycoprobe and an anticancer drug onto a single GO surface. In addition to imaging ability, this material displays improved toxicity for liver cancer cells that over express the glycoprotein receptor, when compared to the control cells.
细胞间糖配体 - 受体相互作用与许多疾病相关过程有关。靶向这些受体的有效工具可能有助于疾病的诊疗。然而，由于它们的结合亲和力较低，需要多价呈现糖配体以增加与跨膜受体的亲和力。虽然先前的策略侧重于将糖配体共价偶联到合成主链上，但我们在此表明，使用氧化石墨烯（GO）可大大增强小分子荧光糖探针的细胞和组织成像能力。我们确定具有最佳尺寸的GO可作为聚集平台，以加强糖探针与其在癌细胞上的选择性受体的相互作用。在荷瘤小鼠的异种移植组织中一直观察到这种现象。利用这一原理，我们进一步通过将糖探针和抗癌药物共组装到单个GO表面构建了一种超分子糖复合物。与对照细胞相比，这种材料除了具有成像能力外，对过表达糖蛋白受体的肝癌细胞还显示出更高的毒性。
