Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy

被引:55
作者
Jo, Seong-Min [1 ]
Wurm, Frederik R. [1 ]
Landfester, Katharina [1 ]
机构
[1] Max Planck Inst Polymer Res, Ackermannweg 10, D-55128 Mainz, Germany
关键词
Nanoreactor; oxidative cancer therapy; enzyme reactions; glucose oxidase; enzymatic therapeutics; enzyme protection; INDUCED APOPTOSIS; GLUCOSE; CELLS; ACTIVATION; PRODRUG; PATHWAY;
D O I
10.1021/acs.nanolett.9b04263
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core-shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization.
引用
收藏
页码:526 / 533
页数:8
相关论文
共 34 条
  • [1] Hydrogen peroxide-mediated cytosolic acidification is a signal for mitochondrial translocation of Bax during drug-induced apoptosis of tumor cells
    Ahmad, KA
    Iskandar, KB
    Hirpara, JL
    Clement, MV
    Pervaiz, S
    [J]. CANCER RESEARCH, 2004, 64 (21) : 7867 - 7878
  • [2] Apoptotic and necrotic blebs in epithelial cells display similar neck diameters but different kinase dependency
    Barros, LF
    Kanaseki, T
    Sabirov, R
    Morishima, S
    Castro, J
    Bittner, CX
    Maeno, E
    Ando-Akatsuka, Y
    Okada, Y
    [J]. CELL DEATH AND DIFFERENTIATION, 2003, 10 (06) : 687 - 697
  • [3] Enzyme Encapsulated Hollow Silica Nanospheres for Intracellular Biocatalysis
    Chang, Feng-Peng
    Hung, Yann
    Chang, Jen-Hsuan
    Lin, Chen-Han
    Mou, Chung-Yuan
    [J]. ACS APPLIED MATERIALS & INTERFACES, 2014, 6 (09) : 6883 - 6890
  • [4] Enhanced Phototherapy by Nanoparticle-Enzyme via Generation and Photolysis of Hydrogen Peroxide
    Chang, Kaiwen
    Liu, Zhihe
    Fang, Xiaofeng
    Chen, Haobin
    Men, Xiaoju
    Yuan, Ye
    Sun, Kai
    Zhang, Xuanjun
    Yuan, Zhen
    Wu, Changfeng
    [J]. NANO LETTERS, 2017, 17 (07) : 4323 - 4329
  • [5] Discrepancy between the effects of morronside on apoptosis in human embryonic lung fibroblast cells and lung cancer A549 cells
    Chen, Jian-Ping
    Xu, De-Guo
    Yu, Xiao-Yi
    Zhao, Feng-Ming
    Xu, Dong-Qing
    Zhang, Xu
    Cai, Bao-Chang
    Wang, Ming-Yan
    [J]. ONCOLOGY LETTERS, 2014, 7 (04) : 927 - 932
  • [6] Industrial applications of enzyme biocatalysis: Current status and future aspects
    Choi, Jung-Min
    Han, Sang-Soo
    Kim, Hak-Sung
    [J]. BIOTECHNOLOGY ADVANCES, 2015, 33 (07) : 1443 - 1454
  • [7] Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu
    Clément, MV
    Ponton, A
    Pervaiz, S
    [J]. FEBS LETTERS, 1998, 440 (1-2): : 13 - 18
  • [8] Glucose oxidase mediated targeted cancer-starving therapy by biotinylated self-assembled vesicles
    Dinda, Soumik
    Sarkar, Saheli
    Das, Prasanta Kumar
    [J]. CHEMICAL COMMUNICATIONS, 2018, 54 (71) : 9929 - 9932
  • [9] Activation of caspase 3 in HL-60 cells exposed to hydrogen peroxide
    DiPietrantonio, AM
    Hsieh, TC
    Wu, JM
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 255 (02) : 477 - 482
  • [10] Glucose-Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy
    Fan, Wenpei
    Lu, Nan
    Huang, Peng
    Liu, Yi
    Yang, Zhen
    Wang, Sheng
    Yu, Guocan
    Liu, Yijing
    Hu, Junkai
    He, Qianjun
    Qu, Junle
    Wang, Tianfu
    Chen, Xiaoyuan
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2017, 56 (05) : 1229 - 1233