Receptor-targeting fluorescence imaging and theranostics using a graphene oxide based supramolecular glycocomposite

Receptor-targeting fluorescence imaging and theranostics using a graphene oxide based supramolecular glycocomposite
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DOI:
10.1039/c5tb02057c
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发表时间:
2015-01-01
影响因子:
7
通讯作者:
He, Xiao-Peng
He, Xiao-Peng
中科院分区:
工程技术2区
文献类型:
--
作者:
Ji, Ding-Kun;Zhang, Yue;He, Xiao-Peng

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细胞间糖配体-受体相互作用涉及许多疾病相关过程。靶向这些受体的有效工具可能有助于疾病治疗诊断。然而,由于其低结合亲和力,需要糖配体的多价呈递以增加与跨膜受体的亲合力。虽然以前的策略集中在共价偶联的糖配体的合成骨架,我们在这里表明,使用氧化石墨烯(GO)大大提高了细胞和组织成像能力的小分子荧光糖探针。我们确定具有最佳尺寸的GO可以作为聚类平台,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,我们通过将糖探针和抗癌药物共组装到单个GO表面上,进一步构建了超分子糖复合物。除了成像能力,与对照细胞相比,该材料对过表达糖蛋白受体的肝癌细胞显示出改善的毒性。
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.