Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy
Abstract Many metal complexes not only had excellent cytotoxic antitumor effects but also could function as a positive immunomodulatory to improve antitumor effects by modifying the local tumor microenvironment. Herein, a dual-target nanotherapeutics (MP3/ACPP/AE105@NPs) with uPAR targeting and tumo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | NPG Asia Materials |
| Online Access: | https://doi.org/10.1038/s41427-023-00473-0 |
| _version_ | 1797274195578585088 |
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| author | Jinggong Liu Wenying Li Yongpeng Lin Yongjun Peng Meixiao Zhan Haoqiang Lai Yanzhou Chang Yongjin Li Ka-hing Wong Bolai Chen Tianfeng Chen |
| author_facet | Jinggong Liu Wenying Li Yongpeng Lin Yongjun Peng Meixiao Zhan Haoqiang Lai Yanzhou Chang Yongjin Li Ka-hing Wong Bolai Chen Tianfeng Chen |
| author_sort | Jinggong Liu |
| collection | DOAJ |
| description | Abstract Many metal complexes not only had excellent cytotoxic antitumor effects but also could function as a positive immunomodulatory to improve antitumor effects by modifying the local tumor microenvironment. Herein, a dual-target nanotherapeutics (MP3/ACPP/AE105@NPs) with uPAR targeting and tumor microenvironment-responsive ability was developed by using AE105 as the targeting ligand and ACPP as the tumor microenvironment-responsive peptide to locate the metal complex to cells. Assisted by the surface modification, MP3/ACPP/AE105@NPs demonstrated excellent cellular uptake of the drugs in in vitro experiments, thereby enhancing the therapeutic utility of the loaded metal complex. The nanotherapeutics induced the excessive ROS generation by inhibiting the activity of TrxR and modulated those proteins which were related to metastasis through inhibiting ERK/AKT activation mediated by FAK in MDA-MB-231 cells. This nanotherapeutics could also significantly improve the therapeutic benefits in vivo accompanied by reduced toxic side effects. Importantly, MP3/ACPP/AE105@NPs treatment stimulated immunotherapeutic response, which was indicated by the activation of tumor-infiltrated cytotoxic T cells, and improved the maturation of dendritic cells (DCs), and the proliferation-inhibitory effect of tumor-associated M2 macrophages. Taken together, the results suggested that this dual-targeted nanotherapeutics offered new opportunities for boosting the synergistic treatment of breast cancer with chemotherapy and immunotherapy. |
| first_indexed | 2024-03-07T14:54:54Z |
| format | Article |
| id | doaj.art-ce78b14bbd344cbfa7db01e2530c7eef |
| institution | Directory Open Access Journal |
| issn | 1884-4057 |
| language | English |
| last_indexed | 2024-03-07T14:54:54Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | NPG Asia Materials |
| spelling | doaj.art-ce78b14bbd344cbfa7db01e2530c7eef2024-03-05T19:29:37ZengNature PortfolioNPG Asia Materials1884-40572023-04-0115111410.1038/s41427-023-00473-0Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapyJinggong Liu0Wenying Li1Yongpeng Lin2Yongjun Peng3Meixiao Zhan4Haoqiang Lai5Yanzhou Chang6Yongjin Li7Ka-hing Wong8Bolai Chen9Tianfeng Chen10Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Interventional Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Interventional Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan UniversityOrthopedics Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Interventional Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Interventional Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan UniversityDepartment of Chemistry, Jinan UniversityDepartment of Chemistry, Jinan UniversityOrthopedics Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineResearch Institute for Future Food, Department of Food Science and Nutrition, The Hong Kong Polytechnic UniversityOrthopedics Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Interventional Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan UniversityAbstract Many metal complexes not only had excellent cytotoxic antitumor effects but also could function as a positive immunomodulatory to improve antitumor effects by modifying the local tumor microenvironment. Herein, a dual-target nanotherapeutics (MP3/ACPP/AE105@NPs) with uPAR targeting and tumor microenvironment-responsive ability was developed by using AE105 as the targeting ligand and ACPP as the tumor microenvironment-responsive peptide to locate the metal complex to cells. Assisted by the surface modification, MP3/ACPP/AE105@NPs demonstrated excellent cellular uptake of the drugs in in vitro experiments, thereby enhancing the therapeutic utility of the loaded metal complex. The nanotherapeutics induced the excessive ROS generation by inhibiting the activity of TrxR and modulated those proteins which were related to metastasis through inhibiting ERK/AKT activation mediated by FAK in MDA-MB-231 cells. This nanotherapeutics could also significantly improve the therapeutic benefits in vivo accompanied by reduced toxic side effects. Importantly, MP3/ACPP/AE105@NPs treatment stimulated immunotherapeutic response, which was indicated by the activation of tumor-infiltrated cytotoxic T cells, and improved the maturation of dendritic cells (DCs), and the proliferation-inhibitory effect of tumor-associated M2 macrophages. Taken together, the results suggested that this dual-targeted nanotherapeutics offered new opportunities for boosting the synergistic treatment of breast cancer with chemotherapy and immunotherapy.https://doi.org/10.1038/s41427-023-00473-0 |
| spellingShingle | Jinggong Liu Wenying Li Yongpeng Lin Yongjun Peng Meixiao Zhan Haoqiang Lai Yanzhou Chang Yongjin Li Ka-hing Wong Bolai Chen Tianfeng Chen Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy NPG Asia Materials |
| title | Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy |
| title_full | Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy |
| title_fullStr | Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy |
| title_full_unstemmed | Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy |
| title_short | Tumor microenvironment-responsive metal nanotherapeutics for breast cancer chemo-/immunotherapy |
| title_sort | tumor microenvironment responsive metal nanotherapeutics for breast cancer chemo immunotherapy |
| url | https://doi.org/10.1038/s41427-023-00473-0 |
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