Engineered redox-responsive PEG detachment mechanism in PEGylated nano-graphene oxide for intracellular drug delivery.
Engineered redox-responsive PEG detachment mechanism in PEGylated nano-graphene oxide for intracellular drug delivery.
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聚乙二醇化纳米氧化石墨烯中设计的氧化还原响应性 PEG 分离机制，用于细胞内药物输送。
DOI：
10.1002/smll.201101613
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发表时间：
2012-03
期刊：
影响因子：
13.3
通讯作者：
Shi, Donglu
中科院分区：
文献类型：
--
作者：
Song, Yanyan;Li, Xuequan;Li, Yongyong;Shi, Donglu
在生物医学应用中，聚乙二醇（PEG）功能化一直是修饰纳米载体（例如纳米氧化石墨烯）以满足特定生物学要求的主要方法。然而，PEG 壳的掺入造成了显着的扩散障碍，对负载药物的释放产生不利影响。本研究通过采用氧化还原响应 PEG 分离机制解决了这个关键问题。开发了一种具有氧化还原响应性可拆卸 PEG 外壳的聚乙二醇化纳米氧化石墨烯 (NGO-SS-mPEG)，可以在肿瘤相关的谷胱甘肽 (GSH) 水平快速释放封装的有效负载。接枝到 NGO 片材上的 PEG 壳赋予纳米复合材料较高的生理溶解度和循环稳定性。在细胞内 GSH 刺激下，它可以选择性地与 NGO 分离。研究表明，表面工程结构可加速 NGO-SS-mPEG 中盐酸阿霉素 (DXR) 的释放，速度比不含 GSH 的情况快 1.55 倍。共聚焦显微镜显示 HeLa 细胞中 NGO-SS-mPEG 内吞作用的清晰证据，主要积累在细胞质中。此外，当将带有二硫键连接的 PEG 外壳的 DXR 负载 NGO 内化到 HeLa 细胞中时，DXR 在升高的 GSH 还原环境中有效释放，如共焦显微镜和流式细胞术实验中所观察到的。重要的是，细胞增殖的抑制与 DXR 快速释放导致的细胞内 GSH 浓度增加直接相关。
In biomedical applications, polyethylene glycol (PEG) functionalization has been a major approach to modify nanocarriers such as nano-graphene oxide for particular biological requirements. However, incorporation of a PEG shell poses a significant diffusion barrier that adversely affects the release of the loaded drugs. This study addresses this critical issue by employing a redox-responsive PEG detachment mechanism. A PEGylated nano-graphene oxide (NGO-SS-mPEG) with redox-responsive detachable PEG shell is developed that can rapidly release an encapsulated payload at tumor-relevant glutathione (GSH) levels. The PEG shell grafted onto NGO sheets gives the nanocomposite high physiological solubility and stability in circulation. It can selectively detach from NGO upon intracellular GSH stimulation. The surface-engineered structures are shown to accelerate the release of doxorubicin hydrochloride (DXR) from NGO-SS-mPEG 1.55 times faster than in the absence of GSH. Confocal microscopy shows clear evidence of NGO-SS-mPEG endocytosis in HeLa cells, mainly accumulated in cytoplasm. Furthermore, upon internalization of DXR-loaded NGO with a disulfide-linked PEG shell into HeLa cells, DXR is effectively released in the presence of an elevated GSH reducing environment, as observed in confocal microscopy and flow cytometric experiments. Importantly, inhibition of cell proliferation is directly correlated with increased intracellular GSH concentrations due to rapid DXR release.
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