SIOC English
有机化学
高级检索

有机化学 >

2013 , Vol. 33 >Issue 03: 573 - 580

DOI: https://doi.org/10.6023/cjoc201211033

研究论文

功能化石墨烯负载冬凌草甲素抗肿瘤制剂的研究

  • 徐志远 ,
  • 李永军 ,
  • 史萍 ,
  • 王博婵 ,
  • 黄晓宇
展开
  • a 华东理工大学材料科学与工程学院 上海 200237;
    b 生物反应器工程国家重点实验室 上海 200237;
    c 中国科学院上海有机化学研究所 上海 200032;
    d 聚合物分子工程国家重点实验室(复旦大学) 上海 200043

收稿日期: 2012-11-16

  修回日期: 2012-12-01

  网络出版日期: 2012-12-07

基金资助

国家自然科学基金(Nos. 31100549, 21204098)、上海市青年科技启明星跟踪计划(No. 11QH1402800)和上海市生物医药科技重点(No. 10431903000)资助项目.

收起

Functionalized Graphene Oxide as a Nanocarrier for Loading and Delivering of Oridonin

  • Xu Zhiyuan ,
  • Li Yongjun ,
  • Shi Ping ,
  • Wang Bochan ,
  • Huang Xiaoyu
Expand
  • a School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237;
    b The State Key Laboratory of Bioreactor Engineering, Shanghai 200237;
    c Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032;
    d State Key Laboratory of Molecular Engineering of Polymers (Fudan University), Shanghai 200043

Received date: 2012-11-16

  Revised date: 2012-12-01

  Online published: 2012-12-07

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 31100549, 21204098), the Shanghai Rising Star Program (No. 11QH1402800), and the Shanghai Scientific and Technological Innovation Project (No. 10431903000).

Fold

摘要

通过改进的Hummers法制备氧化石墨烯(GO), 利用酰胺化反应将端基为氨基的六臂聚乙二醇(PEG)连到氧化石墨烯表面, 改善其水溶性和生物相容性. 原子力显微镜(AFM)数据表明所制备的GO-PEG尺寸小于250 nm, 稳定性试验证明GO-PEG在水和PBS缓冲液中可以很好地分散. 利用制备的GO-PEG作为药物载体, 通过物理共混的方法负载疏水性抗肿瘤药物——冬凌草甲素. 紫外光谱法测得载药率高达105%, 远高于一般其他的药物载体. 选择肺癌细胞A549和乳腺癌细胞MCF-7对载药体系的细胞毒性进行了研究, 结果表明即使在高达100 mg/L的浓度下培养48 h, 载体GO-PEG对两种细胞仍然具有很小的毒性(相对细胞存活率＞85%), 而通过载体负载后冬凌草甲素的疗效有所增强, 对细胞具有更大的杀伤作用.

关键词： 氧化石墨烯; 冬凌草甲素; 药物传输

本文引用格式

徐志远 , 李永军 , 史萍 , 王博婵 , 黄晓宇 . 功能化石墨烯负载冬凌草甲素抗肿瘤制剂的研究[J]. 有机化学, 2013 , 33(03) : 573 -580 . DOI: 10.6023/cjoc201211033

Abstract

Graphene oxide (GO) was prepared by modified Hummers method firstly. In order to improve its water solubility and biocompatibility, 6-armed PEG was grafted onto GO via an amidation process. The size of GO-PEG was less than 250 nm and stability test indicated excellent dispersibility of GO-PEG in water and PBS buffer. Furthermore, oridonin, a widely used cancer chemotherapy drug, is adsorbed onto GO-PEG via blending. The drug loading ratio was determined to be as high as 105%, which was much higher than other common drug carriers. A549 lung cancer cell and MCF-7 breast cancer cell were chosen to study the cytotoxicity of GO-PEG/oridonin, GO-PEG, and free oridonin. The results demonstrated that GO-PEG did not show obvious toxicity (relative cell viability＞85%), even cultivated for 48 h at a relatively high concentration of 100 mg/L. Compared to oridonin, the GO-PEG/oridonin nanocarrier shows higher cytotoxicity in A549 and MCF-7 cells.

Key words： graphene oxide; oridonin; drug delivery

参考文献

[1] (a) Zhang, D. Y.; Li, Z. Y.; Shi, L. Y.; Wu, X. M.; Hua, W. Y. Chin. J. Org. Chem. 2008, 28, 1911 (in Chinese).
(张大永, 李子元, 施连勇, 吴晓明, 华唯一, 有机化学, 2008, 28, 1911.)
(b) Han, Q. B.; Mei, S. X.; Jiang, B.; Zhao, A. H.; Sun, H. D. Chin. J. Org. Chem. 2003, 23, 270 (in Chinese).
(韩全斌, 梅双喜, 姜北, 赵爱华, 孙汉董, 有机化学, 2003, 23, 270.)

[2] Ran, Q.; Xu, J. Y.; Wu, X. M.; Hua, W. Y. Pharm. Clin. Res. 2007, 15, 2 (in Chinese).
(冉倩, 徐进宜, 吴晓明, 华唯一, 药学与临床研究, 2007, 15, 2.)

[3] (a) Yan, X. B.; Lei, M.; Zhang, J. Y.; Liu, H. M. Chin. J. Org. Chem. 2005, 25, 222 (in Chinese).
(阎学斌, 雷萌, 张建业, 刘宏民, 有机化学, 2005, 25, 222.)
(b) Xu, J. Y.; Yang, J. Y.; Ran, Q.; Wang, L.; Liu, J.; Wang, Z. X.; Wu, X. M.; Hua, W. Y.; Yuan, S. T.; Zhang, L. Y.; Shen, M. Q.; Ding, Y. F. Bioorg. Med. Chem. Lett. 2008, 18, 4741.

[4] (a) Yokoyama, M.; Satoh, A.; Sakurai, Y. Okano, T.; Matsumura, Y.; Kakizoe, T.; Kataoka, K. J. Controlled Release 1998, 55, 219.
(b) Kwon, G. S.; Okano, T. Adv. Drug. Delivery Rev. 1996, 21, 107.

[5] (a) Liu, Z.; Chen, K.; Davis, C.; Sherlock, S.; Cao, Q. Z.; Chen, X. Y.; Dai, H. J. Cancer. Res. 2008, 68, 6625.
(b) Huang, X. W.; Guo, L. N.; Lu, G. L.; Huang, X.; Zhang, Y. Q.; Huang, X. Y. Acta. Chim. Sinica 2009, 67, 1363 (in Chinese).
(黄晓炜, 顾丽娜, 陆国林, 黄啸, 张亚琴, 黄晓宇, 化学学报, 2009, 67, 1363.)
(c) Chen, S. Y.; Zhao, X. R.; Chen, J. Y.; Chen, J.; Kuznetsova, L.; Wong, S. S.; Ojima, I. Bioconjugate Chem. 2010, 21, 979.

[6] Zhang, Y. B.; Kou, X.; Lu, J. S.; Wang, G. H. J. Chin. Med. Mater. 1999, 22(4), 204 (in Chinese).
(张雁冰, 寇娴, 卢建莎, 王桂红, 中药材, 1999, 22(4), 204.)

[7] Shi, S. P.; Feng, N. P.; Yu, J.; Wu, P. Y.; Wei, L. Chin. J. Nat. Med. 2005, 3(5), 291 (in Chinese).
(施水萍, 冯年平, 余婧, 武培怡, 魏莉, 中国天然药物, 2005, 3(5), 291.)

[8] Xing, J.; Zhang, D. R.; Zhang, X. S.; Gao, L. Chin. Pharm. J. 2007, 42, 1006 (in Chinese).
(邢洁, 张典瑞, 张学顺, 高磊, 中国药学杂志, 2007, 42, 1006.)

[9] (a) Novoselov, K. S.; Geim, A. K.; Morozov, S. V.; Jiang, D.; Zhang, Y.; Dubonos, S. V.; Grigorieva, I. V.; Firsov, A. A. Science 2004, 306, 666.
(b) Dai, J.; Lang, M. D. Acta Chim. Sinica 2012, 70, 1237 (in Chinese)
(戴静, 郎美东, 化学学报, 2012, 70, 1237.)
(c) Deng, Y.; Li, Y. J.; Dai, J.; Lang, M. D.; Huang, X. Y. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 1582.

[10] (a) He, H. Y.; Klinowski, J.; Forster, M.; Lerf, A. Chem. Phys. Lett. 1998, 287, 53.
(b) Deng, Y.; Li, Y. J.; Dai, J.; Lang, M. D.; Huang, X. Y. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 4747.
(c) Chen, X. Y.; Shi, Y. L.; Yang, D.; Hu, J. H.; Yang, P. Y. Acta Chim. Sinica 2012, 70, 817 (in Chinese).
(陈小乙, 石远琳, 杨东, 胡建华, 杨芃原, 化学学报, 2012, 70, 817.)

[11] (a) Liu, Z.; Robinson, J. T.; Sun, X. M.; Dai, H. J. J. Am. Chem. Soc. 2008, 130, 10876.
(b) Bao, H. Q.; Pan, Y. Z.; Ping, Y.; Sahoo, N. G.; Wu, T. F.; Li, L.; Li, J.; Gan, L. H. Small 2011, 7, 1569.

[12] (a) Xu, Y. X.; Sheng, K. X.; Li, C.; Shi, G. Q. J. Mater. Chem. 2011, 21, 7376.
(b) Chen, J.; Sheng, K. X.; Luo, P. H.; Li, C.; Shi, G. Q. Adv. Mater. 2012, 24, 4649.

[13] Zhang, R. Y.; Hummelgard, M.; Lv, G.; Olin, H. Carbon 2011, 49, 1126.

[14] Kuang, C. C.; Du, W.; Wang, W. Herald Med. 2010, 29, 1334 (in Chinese).
(匡长春, 杜葳, 王薇, 医药导报, 2010, 29, 1334.)

[15] Chizhik, S. A.; Buzaneva, E. V.; Gorchinskiy, A. D. Chem. Mater. 1999, 11, 771.

[16] Sun, X. M.; Liu, Z.; Welsher, K.; Robinson, J. T.; Goodwin, A.; Zaric, S.; Dai, H. Nano Res. 2008, 1, 203.
Options
文章导航

/

〈 〉