文献类型：期刊文献

英文题名：PEGylated graphene oxide as a nanocarrier of the disulfide prodrug of podophyllotoxin for cancer therapy

作者：Liu, Yajing[1,2];Lv, Xiaoguang[1,2];Xia, Shengli[3];Hao, Bingjie[4];Huang, Xiaoyu[4];Shi, Ping[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Key Lab Adv Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Inst Fine Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Shanghai Univ Med & Hlth Sci, Affiliated Zhoupu Hosp, Dept Orthoped, 1500 Zhoupu Zhouyuan Rd, Shanghai 201318, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Organ Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China

年份：2020

卷号：22

期号：9

外文期刊名：JOURNAL OF NANOPARTICLE RESEARCH

收录：;EI(收录号：20203809193806);WOS:【SCI-EXPANDED(收录号:WOS:000568305400001)】；

基金：This work was sponsored by grants from the National Natural Science Foundation of China (31671309) and the Training Planned Fund of Academic Leaders, Shanghai Pudong New Area Health System (PWR 12018-09).

语种：英文

外文关键词：Nanocarrier; GO-PEG; DCM-S-PPT; GSH; Tumor-bearing mice; Nanomedicine

摘要：Efficient drug delivery systems are required to increase drug concentrations at tumor sites and to reduce the side effects on normal cells. In this work, we developed a nanoscale drug delivery system based on graphene oxide (GO) and used it to load a disulfide prodrug of podophyllotoxin (DCM-S-PPT), which was linked by a thiol-specific cleavable disulfide bond. In order to improve the biocompatibility in physiological solution, GO was functionalized with 6-armed polyethylene glycol (PEG) and characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. By atomic force microscopy, the size distribution of the nanoparticles was shown to be 25 similar to 250 nm. DCM-S-PPT was loaded on GO-PEG via p-p stacking and hydrophobic interactions. The loading rate reached 138%. In vitro cytotoxicity assay showed that GO-PEG/DCM-S-PPT inhibited the proliferation of human cervical adenocarcinoma HeLa cells more than that of human normal kidney 293T cells, which was attributed to the different intracellular concentrations of GSH. After intravenous injection in mice bearing tumors, GO-PEG/DCM-S-PPT showed the better antitumor activity and less side effects than those of DCM-S-PPT and PPT. Compared with DCM-S-PPT or PPT, GO-PEG/DCM-S-PPT complex showed the best tumor-targeting and specific drug release. Our results provide a novel strategy for the combination of nanocarriers and modified chemotherapy drugs in the future.