Journal
ADVANCED SCIENCE
Volume 7, Issue 16, Pages -Publisher
WILEY
DOI: 10.1002/advs.201903323
Keywords
hepatoma therapy; iron oxide nanoparticles; iron transport systems; tumoricidal autophagy
Categories
Funding
- National Natural Science Foundation of China [81771968, 81773222, 31400719]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine [20181705]
- Shanghai Municipal Commission of Health and Family Planning [201840020]
- Shanghai Talent Development Fund [2017053]
- Shanghai Jiao Tong University [ZH2018ZDA05]
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The combined treatment with nanoparticles and autophagy inhibitors, such as chloroquine (CQ) and hydroxychloroquine (HCQ), is extensively explored for cancer therapy. However, the toxicity of autophagy inhibitors and their unselective for tumoricidal autophagy have seriously hindered the application of the combined treatment. In this study, a carboxy-functional iron oxide nanoparticle (Fe2O3@DMSA) is designed and identified to significantly exert an antitumor effect without adding CQ or HCQ. Further investigation indicates that the effective inhibition effect of Fe2O3@DMSA alone on hepatoma growth is triggered by inhibiting the fusion of autophagosomes and lysosomes to enhance tumoricidal autophagy, which is induced by intracellular iron-retention-induced sustained reactive oxygen species (ROS) production. Furthermore, in two hepatoma-bearing mouse models, Fe2O3@DMSA alone effectively suppresses the growth of tumors without obvious toxic side effects. These studies offer a promising strategy for cancer therapy.
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