An artificial-enzyme-equipped immunoregulator blocks platelet-mediated breast cancer hematogenous metastasis
Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering "micro-thrombi," CTCs evade immune surveillance in circulation, th...
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| Vydáno v: | Biomaterials Ročník 322; s. 123380 |
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| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Netherlands
Elsevier Ltd
01.11.2025
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| Témata: | |
| ISSN: | 0142-9612, 1878-5905, 1878-5905 |
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| Abstract | Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering "micro-thrombi," CTCs evade immune surveillance in circulation, thereby promoting hematogenous tumor metastasis. Based on this, we designed a self-assembling nanoenzyme drug GSNO@B (NO donor-modified GOx self-assembled with the hydrophobic drug BMS-202) against platelet-mediated tumor metastasis. This strategy involves the depletion of glucose by GOx, which inhibits platelets activity and reduces forming the micro-aggregation. Concurrently, the nanoenzyme in situ releases NO further diminishes the protective adhesion and micro-aggregation of platelet on the tumor cells surface, thereby exposing them in shear forces and immune recognition in the circulatory system. Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway. |
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| AbstractList | Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering "micro-thrombi," CTCs evade immune surveillance in circulation, thereby promoting hematogenous tumor metastasis. Based on this, we designed a self-assembling nanoenzyme drug GSNO@B (NO donor-modified GOx self-assembled with the hydrophobic drug BMS-202) against platelet-mediated tumor metastasis. This strategy involves the depletion of glucose by GOx, which inhibits platelets activity and reduces forming the micro-aggregation. Concurrently, the nanoenzyme in situ releases NO further diminishes the protective adhesion and micro-aggregation of platelet on the tumor cells surface, thereby exposing them in shear forces and immune recognition in the circulatory system. Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway. Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering "micro-thrombi," CTCs evade immune surveillance in circulation, thereby promoting hematogenous tumor metastasis. Based on this, we designed a self-assembling nanoenzyme drug GSNO@B (NO donor-modified GOx self-assembled with the hydrophobic drug BMS-202) against platelet-mediated tumor metastasis. This strategy involves the depletion of glucose by GOx, which inhibits platelets activity and reduces forming the micro-aggregation. Concurrently, the nanoenzyme in situ releases NO further diminishes the protective adhesion and micro-aggregation of platelet on the tumor cells surface, thereby exposing them in shear forces and immune recognition in the circulatory system. Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway.Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering "micro-thrombi," CTCs evade immune surveillance in circulation, thereby promoting hematogenous tumor metastasis. Based on this, we designed a self-assembling nanoenzyme drug GSNO@B (NO donor-modified GOx self-assembled with the hydrophobic drug BMS-202) against platelet-mediated tumor metastasis. This strategy involves the depletion of glucose by GOx, which inhibits platelets activity and reduces forming the micro-aggregation. Concurrently, the nanoenzyme in situ releases NO further diminishes the protective adhesion and micro-aggregation of platelet on the tumor cells surface, thereby exposing them in shear forces and immune recognition in the circulatory system. Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway. |
| ArticleNumber | 123380 |
| Author | Sun, Fushan Duan, Xiaohui Zhang, Fang Wang, Yu Chang, Yunhua Hu, Ben Quan, Xiaolong Lin, Huimin Zhang, Fengling Wang, Jigang Yu, Meng |
| Author_xml | – sequence: 1 givenname: Ben surname: Hu fullname: Hu, Ben organization: NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China – sequence: 2 givenname: Huimin surname: Lin fullname: Lin, Huimin organization: NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China – sequence: 3 givenname: Xiaolong surname: Quan fullname: Quan, Xiaolong organization: NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China – sequence: 4 givenname: Fushan surname: Sun fullname: Sun, Fushan organization: NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China – sequence: 5 givenname: Fengling surname: Zhang fullname: Zhang, Fengling organization: NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China – sequence: 6 givenname: Fang surname: Zhang fullname: Zhang, Fang organization: Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China – sequence: 7 givenname: Yu surname: Wang fullname: Wang, Yu organization: Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China – sequence: 8 givenname: Yunhua surname: Chang fullname: Chang, Yunhua organization: Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades F-75015, Paris, 75005, France – sequence: 9 givenname: Jigang surname: Wang fullname: Wang, Jigang email: jgwang@icmm.ac.cn organization: Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineer Technology Research and Development Center, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518020, China – sequence: 10 givenname: Xiaohui orcidid: 0000-0002-2224-0887 surname: Duan fullname: Duan, Xiaohui email: duanxh5@mail.sysu.edu.cn organization: Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China – sequence: 11 givenname: Meng orcidid: 0000-0003-1039-9687 surname: Yu fullname: Yu, Meng email: yumeng999@smu.edu.cn organization: NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China |
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| Keywords | Glucose oxidase Drug delivery Platelet inhibition Nanomedicine Tumor metastasis |
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| SubjectTerms | Animals Blood Platelets - drug effects Blood Platelets - pathology Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Line, Tumor Drug delivery Female Glucose oxidase Humans Mice Mice, Inbred BALB C Mice, Nude Nanomedicine Neoplasm Metastasis Neoplastic Cells, Circulating - drug effects Neoplastic Cells, Circulating - pathology Platelet inhibition Tumor metastasis |
| Title | An artificial-enzyme-equipped immunoregulator blocks platelet-mediated breast cancer hematogenous metastasis |
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