文献类型：期刊文献

英文题名：Vacuolization in Cytoplasm and Cell Membrane Permeability Enhancement Triggered by Micrometer-Sized Graphene Oxide

作者：Wu, Congyu[1];Wang, Chong[2];Zheng, Jing[2];Luo, Chao[2];Li, Yanfang[2];Guo, Shouwu[1];Zhang, Jingyan[2]

机构：[1]Shanghai Jiao Tong Univ, Sch Elect Informat & Elect Engn, Dept Elect Engn, Shanghai 200240, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2015

卷号：9

期号：8

起止页码：7913

外文期刊名：ACS NANO

收录：;EI(收录号：20153501215296);WOS:【SCI-EXPANDED(收录号:WOS:000360323300020)】；

基金：This research was carried out with financial support from the national "973 Program" of China (Nos. 2014CB260411, 2015CB931801), National Science foundation of China (No. 11374205), the State Key Laboratory of Bioreactor Engineering (No. 2060204), 111 Project (No. 807023), the Shanghai Committee of Science and Technology (Nos. 11DZ2260600 and 12 nm0503500), and national "863" Program of China (No. 2012AA022603) for financial support of this work. J. Zhang and S. Guo designed the project. C. Wu, C. Wang, and C. Luo carried out the molecular level experiments. C. Wu prepared and characterized the mGO. J. Zheng contributed to the nerve cell related experiments. C. Luo and Y. Li carried out Western and RT-PCR experiments. J. Zhang, S. Guo, and C. Wu wrote the manuscript.

语种：英文

外文关键词：micrometer-sized graphene oxide; mGO; aquaporins; AQPs; cell membrane

摘要：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.