Cao Tianye, You Peihong, Zhou Xiaobao, Luo Jianmin, Xu Xiaoping, Zhou Zhiguo, Yang Shiping, Zhang Yingjian, Yang Hong, Wang Mingwei
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Center for Biomedical Imaging, Fudan University, Shanghai Engineering Research Center for Molecular Imaging Probes, No. 270 Dong'An Road, Shanghai 200032, China.
J Mater Chem B. 2016 Oct 21;4(39):6446-6453. doi: 10.1039/c6tb01892k. Epub 2016 Sep 26.
PEGylated nanosized graphene oxides (NGO-PEG) and related derivatives have attracted extensive attention owing to their unique properties, which confer significant theranostic benefits for cancer treatment. The size of NGO-PEG varies largely, from tens of nanometers to micrometers, and the optimal size range with the most efficient tumor retention in vivo remains to be determined. For this purpose, we designed different sizes of NGO-PEG, specifically, ultra-small NGO-PEG (usNGO-PEG, sub-50 nm) and NGO-PEG (over 50 nm) and compared their biological behaviors in vitro and in vivo. Both NGO-PEGs exhibited nearly identical physicochemical properties and low cytotoxicity. Following Cy5.5 tagging, confocal microscopy fluorescence imaging revealed faster and higher dynamic cellular uptake of usNGO-PEG than NGO-PEG. Longitudinal, non-invasive visualization of the NGO-PEGs using single proton emission computed tomography (SPECT) imaging with I-radiolabeling revealed that tumor retention of usNGO-PEG was significantly higher and longer compared to that of NGO-PEG, whereas the blood circulation and biodistribution of both NGO-PEGs were similar in major organs. In conclusion, Sub-50 nm was further confirmed to be the favorable size for efficient tumor accumulation of PEGylated GO via the enhanced permeability and retention (EPR) effect. We propose that the sub-50 nm NGO-PEG designed in this study may be effectively utilized to develop novel PEGylated GO-based nanoplatforms for multifunctional cancer nanotheranostics.
聚乙二醇化纳米氧化石墨烯（NGO-PEG）及其相关衍生物因其独特的性质而备受关注，这些性质为癌症治疗带来了显著的诊疗优势。NGO-PEG的尺寸差异很大，从几十纳米到微米不等，体内肿瘤保留效率最高的最佳尺寸范围仍有待确定。为此，我们设计了不同尺寸的NGO-PEG，具体而言，超小NGO-PEG（usNGO-PEG，小于50纳米）和NGO-PEG（大于50纳米），并比较了它们在体外和体内的生物学行为。两种NGO-PEG都表现出几乎相同的物理化学性质和低细胞毒性。用Cy5.5标记后，共聚焦显微镜荧光成像显示usNGO-PEG比NGO-PEG具有更快、更高的动态细胞摄取。使用I放射性标记的单质子发射计算机断层扫描（SPECT）成像对NGO-PEG进行纵向、非侵入性可视化显示，与NGO-PEG相比，usNGO-PEG的肿瘤保留率显著更高且持续时间更长，而两种NGO-PEG在主要器官中的血液循环和生物分布相似。总之，通过增强渗透和滞留（EPR）效应，进一步证实小于50纳米是聚乙二醇化氧化石墨烯有效肿瘤蓄积的有利尺寸。我们提出，本研究中设计的小于50纳米的NGO-PEG可有效用于开发基于聚乙二醇化氧化石墨烯的新型纳米平台，用于多功能癌症纳米诊疗。
