A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma
ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. Chemotherapy is one of the first-line clinical therapeutic strategies for HCC. Still, the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resista...
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KeAi Communications Co. Ltd.
2025-07-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667325824005351 |
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| author | Chen Guo Rui Dou Linbang Wang Jiayu Zhang Xiaomeng Cai Jiaruo Tang Zhengyuan Huang Xiaoguang Liu Jun Chen Hanqing Chen |
| author_facet | Chen Guo Rui Dou Linbang Wang Jiayu Zhang Xiaomeng Cai Jiaruo Tang Zhengyuan Huang Xiaoguang Liu Jun Chen Hanqing Chen |
| author_sort | Chen Guo |
| collection | DOAJ |
| description | ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. Chemotherapy is one of the first-line clinical therapeutic strategies for HCC. Still, the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resistance caused by insufficient delivery. Herein, we developed a metal-drug self-delivery nanomedicine (FDAH) to improve the chemo/chemodynamic therapeutic efficacy of HCC. The core of FDAH is an iron-based nanoparticle chelated with two clinical drugs, Doxorubicin (DOX) and Plerixafor (AMD3100). Additionally, the nanomedicine is externally modified with a hyaluronic acid (HA) shell, which can prolong the circulation time of the nanoparticles in the bloodstream after intravenous administration. After entering the bloodstream, the nanomedicine reaches the tumor tissue through the EPR effect and is phagocytosed by the tumor cells via HA/CD44-specific interaction. Iron ion-mediated chemodynamic therapy is mediated by the Fenton reaction to generate ROS, causing an imbalance of redox homeostasis within the tumor cells and enhancing the sensitivity of tumor cells to DOX. In addition, AMD3100 intervenes in the CXCL12/CXCR4 axis to influence the infiltration level of immune cells and promote DOX chemotherapy in tumor cells. This work suggests that alleviating immunosuppression via a metal-drug self-delivery system of the CXCR4 inhibitor can effectively improve the DOX chemotherapy and iron ions-mediated chemodynamic therapy. |
| format | Article |
| id | doaj-art-c035ea95a767471f90f5b5a940d022e8 |
| institution | DOAJ |
| issn | 2667-3258 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | KeAi Communications Co. Ltd. |
| record_format | Article |
| series | Fundamental Research |
| spelling | doaj-art-c035ea95a767471f90f5b5a940d022e82025-08-20T02:48:43ZengKeAi Communications Co. Ltd.Fundamental Research2667-32582025-07-01541440145010.1016/j.fmre.2024.12.014A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinomaChen Guo0Rui Dou1Linbang Wang2Jiayu Zhang3Xiaomeng Cai4Jiaruo Tang5Zhengyuan Huang6Xiaoguang Liu7Jun Chen8Hanqing Chen9Department of Gastroenterology and Hepatology, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510320, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Orthopedics, Peking University Third Hospital, Beijing 100191, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Orthopedics, Peking University Third Hospital, Beijing 100191, ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.Department of Gastroenterology and Hepatology, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510320, China; Department of Nutrition & Food Hygiene, School of Public Health, Capital Medical University, Beijing 100069, China; Corresponding authors.ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. Chemotherapy is one of the first-line clinical therapeutic strategies for HCC. Still, the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resistance caused by insufficient delivery. Herein, we developed a metal-drug self-delivery nanomedicine (FDAH) to improve the chemo/chemodynamic therapeutic efficacy of HCC. The core of FDAH is an iron-based nanoparticle chelated with two clinical drugs, Doxorubicin (DOX) and Plerixafor (AMD3100). Additionally, the nanomedicine is externally modified with a hyaluronic acid (HA) shell, which can prolong the circulation time of the nanoparticles in the bloodstream after intravenous administration. After entering the bloodstream, the nanomedicine reaches the tumor tissue through the EPR effect and is phagocytosed by the tumor cells via HA/CD44-specific interaction. Iron ion-mediated chemodynamic therapy is mediated by the Fenton reaction to generate ROS, causing an imbalance of redox homeostasis within the tumor cells and enhancing the sensitivity of tumor cells to DOX. In addition, AMD3100 intervenes in the CXCL12/CXCR4 axis to influence the infiltration level of immune cells and promote DOX chemotherapy in tumor cells. This work suggests that alleviating immunosuppression via a metal-drug self-delivery system of the CXCR4 inhibitor can effectively improve the DOX chemotherapy and iron ions-mediated chemodynamic therapy.http://www.sciencedirect.com/science/article/pii/S2667325824005351Hepatocellular carcinomaMetal-drug self-delivery nanomedicineChemotherapyChemodynamic therapyImmunosuppressive microenvironment |
| spellingShingle | Chen Guo Rui Dou Linbang Wang Jiayu Zhang Xiaomeng Cai Jiaruo Tang Zhengyuan Huang Xiaoguang Liu Jun Chen Hanqing Chen A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma Fundamental Research Hepatocellular carcinoma Metal-drug self-delivery nanomedicine Chemotherapy Chemodynamic therapy Immunosuppressive microenvironment |
| title | A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma |
| title_full | A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma |
| title_fullStr | A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma |
| title_full_unstemmed | A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma |
| title_short | A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma |
| title_sort | metal drug self delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo chemodynamic therapy against hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Metal-drug self-delivery nanomedicine Chemotherapy Chemodynamic therapy Immunosuppressive microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2667325824005351 |
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