DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression
Abstract Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202206707 |
| _version_ | 1797812788765130752 |
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| author | Zuqin Chen Sunfan Li Fangzhou Li Cheng Qin Xianlei Li Guangchao Qing Jinjin Wang Bozhang Xia Fuxue Zhang Liangliang Meng Xing‐Jie Liang Yueyong Xiao |
| author_facet | Zuqin Chen Sunfan Li Fangzhou Li Cheng Qin Xianlei Li Guangchao Qing Jinjin Wang Bozhang Xia Fuxue Zhang Liangliang Meng Xing‐Jie Liang Yueyong Xiao |
| author_sort | Zuqin Chen |
| collection | DOAJ |
| description | Abstract Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO‐micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild‐photothermal chemotherapy strategy based on MTO‐micelles has a promising prospect in the clinical transformation of TNBC treatment. |
| first_indexed | 2024-03-13T07:43:39Z |
| format | Article |
| id | doaj.art-481e5602f5d84781a5a8f1b670e5bc88 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T07:43:39Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-481e5602f5d84781a5a8f1b670e5bc882023-06-03T01:03:32ZengWileyAdvanced Science2198-38442023-06-011016n/an/a10.1002/advs.202206707DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 ExpressionZuqin Chen0Sunfan Li1Fangzhou Li2Cheng Qin3Xianlei Li4Guangchao Qing5Jinjin Wang6Bozhang Xia7Fuxue Zhang8Liangliang Meng9Xing‐Jie Liang10Yueyong Xiao11Medical School of Chinese PLA No. 28 Fuxing Road Beijing 100853 P. R. ChinaSchool of Microelectronics Shanghai University Shanghai 201800 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaMedical School of Chinese PLA No. 28 Fuxing Road Beijing 100853 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaDepartment of Medical Imaging Chinese PAP Force Hospital of Beijing Beijing 100600 P. R. ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 P. R. ChinaDepartment of Radiology The First Medical Center Chinese PLA General Hospital Beijing 100853 P. R. ChinaAbstract Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO‐micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild‐photothermal chemotherapy strategy based on MTO‐micelles has a promising prospect in the clinical transformation of TNBC treatment.https://doi.org/10.1002/advs.202206707chemotherapyDNA damageheat shock proteinmild‐photothermal therapymitoxantronepolymeric micelle |
| spellingShingle | Zuqin Chen Sunfan Li Fangzhou Li Cheng Qin Xianlei Li Guangchao Qing Jinjin Wang Bozhang Xia Fuxue Zhang Liangliang Meng Xing‐Jie Liang Yueyong Xiao DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression Advanced Science chemotherapy DNA damage heat shock protein mild‐photothermal therapy mitoxantrone polymeric micelle |
| title | DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression |
| title_full | DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression |
| title_fullStr | DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression |
| title_full_unstemmed | DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression |
| title_short | DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression |
| title_sort | dna damage inducer mitoxantrone amplifies synergistic mild photothermal chemotherapy for tnbc via decreasing heat shock protein 70 expression |
| topic | chemotherapy DNA damage heat shock protein mild‐photothermal therapy mitoxantrone polymeric micelle |
| url | https://doi.org/10.1002/advs.202206707 |
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