A Selective Nano Cell Cycle Checkpoint Inhibitor Overcomes Leukemia Chemoresistance
Jie Sun
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Liangzhu LaboratoryZhejiang University Medical CenterInstitute of Hematology, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorFan Xia
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorShaoqi Zhang
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Liangzhu LaboratoryZhejiang University Medical CenterInstitute of Hematology, Zhejiang University, Hangzhou, 310058 China
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorBo Zhang
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
WLA Laboratories, Shanghai, 201203 China
Search for more papers by this authorYunan Guan
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorXi Hu
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012 China
Search for more papers by this authorPengpeng Xue
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorShengfei Yang
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorYan Zhou
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Daishun Ling
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
WLA Laboratories, Shanghai, 201203 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Fangyuan Li
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
WLA Laboratories, Shanghai, 201203 China
Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, 310009 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorJie Sun
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Liangzhu LaboratoryZhejiang University Medical CenterInstitute of Hematology, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorFan Xia
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorShaoqi Zhang
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Liangzhu LaboratoryZhejiang University Medical CenterInstitute of Hematology, Zhejiang University, Hangzhou, 310058 China
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorBo Zhang
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
WLA Laboratories, Shanghai, 201203 China
Search for more papers by this authorYunan Guan
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorXi Hu
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012 China
Search for more papers by this authorPengpeng Xue
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorShengfei Yang
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorYan Zhou
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Daishun Ling
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
WLA Laboratories, Shanghai, 201203 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Fangyuan Li
Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240 China
WLA Laboratories, Shanghai, 201203 China
Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, 310009 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
Cell cycle checkpoint activation promotes DNA damage repair, which is highly associated with the chemoresistance of various cancers including acute myeloid leukemia (AML). Selective cell cycle checkpoint inhibitors are strongly demanded to overcome chemoresistance, but remain unexplored. A selective nano cell cycle checkpoint inhibitor (NCCI: citric acid capped ultra-small iron oxide nanoparticles) that can catalytically inhibit the cell cycle checkpoint of AML to boost the chemotherapeutic efficacy of genotoxic agents is now reported. NCCI can selectively accumulate in AML cells and convert H2O2 to •OH to cleave heat shock protein 90, leading to the degradation of ataxia telangiectasia and Rad3-related proteinand checkpoint kinase 1, and the subsequent dysfunction of the G2/M checkpoint. Consequently, NCCI revitalizes the anti-AML efficacy of cytarabine that is previously ineffective both in vitro and in vivo. This study offers new insights into designing selective cell cycle checkpoint inhibitors for biomedical applications.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| smll202300736-sup-0001-SuppMat.pdf20.6 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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