Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy
Abstract 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 ap...
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.201903323 |
| _version_ | 1818133123784769536 |
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| author | Yuexia Xie Jiana Jiang Qianyun Tang Hanbing Zou Xue Zhao Hongmei Liu Ding Ma Chenlei Cai Yan Zhou Xiaojing Chen Jun Pu Peifeng Liu |
| author_facet | Yuexia Xie Jiana Jiang Qianyun Tang Hanbing Zou Xue Zhao Hongmei Liu Ding Ma Chenlei Cai Yan Zhou Xiaojing Chen Jun Pu Peifeng Liu |
| author_sort | Yuexia Xie |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-11T08:47:43Z |
| format | Article |
| id | doaj.art-0a569f48e7464124a981cbbc1b06be8e |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-11T08:47:43Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-0a569f48e7464124a981cbbc1b06be8e2022-12-22T01:14:06ZengWileyAdvanced Science2198-38442020-08-01716n/an/a10.1002/advs.201903323Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal AutophagyYuexia Xie0Jiana Jiang1Qianyun Tang2Hanbing Zou3Xue Zhao4Hongmei Liu5Ding Ma6Chenlei Cai7Yan Zhou8Xiaojing Chen9Jun Pu10Peifeng Liu11State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 ChinaAbstract 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.https://doi.org/10.1002/advs.201903323hepatoma therapyiron oxide nanoparticlesiron transport systemstumoricidal autophagy |
| spellingShingle | Yuexia Xie Jiana Jiang Qianyun Tang Hanbing Zou Xue Zhao Hongmei Liu Ding Ma Chenlei Cai Yan Zhou Xiaojing Chen Jun Pu Peifeng Liu Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy Advanced Science hepatoma therapy iron oxide nanoparticles iron transport systems tumoricidal autophagy |
| title | Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy |
| title_full | Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy |
| title_fullStr | Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy |
| title_full_unstemmed | Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy |
| title_short | Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy |
| title_sort | iron oxide nanoparticles as autophagy intervention agents suppress hepatoma growth by enhancing tumoricidal autophagy |
| topic | hepatoma therapy iron oxide nanoparticles iron transport systems tumoricidal autophagy |
| url | https://doi.org/10.1002/advs.201903323 |
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