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Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects | |
Wang, Changlong1,2; Zhang, Wei3,4,5; He, Yanjie6; Gao, Zirui3,4,5; Liu, Liyuan7; Yu, Siyao6; Hu, Yuxing6; Wang, Shuang1; Zhao, Chaochao3,4,5; Li, Hui7; Shi, Jinan8,9; Zhou, Wu8,9; Li, Feng1,2; Yue, Hua1; Li, Yuhua6,10; Wei, Wei1,2; Ma, Guanghui1,2; Ma, Ding3,4,5 | |
2021-10-25 | |
Source Publication | NATURE NANOTECHNOLOGY
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ISSN | 1748-3387 |
Pages | 17 |
Abstract | Trivalent arsenic (As-III) is a clinically approved treatment agent for patients with promyelocytic leukaemia, but cannot be used for other types of leukaemia due to its toxicity. Here the authors show that different patient-derived leukaemia cells express CD71 and design a ferritin-based nanoparticle for specific delivery of As-III to these cells, demonstrating substantially improved efficacy towards different leukaemia types in animal models, with reduced side effects. Trivalent arsenic (As-III) is an effective agent for treating patients with acute promyelocytic leukaemia, but its ionic nature leads to several major limitations like low effective concentrations in leukaemia cells and substantial off-target cytotoxicity, which limits its general application to other types of leukaemia. Here, building from our clinical discovery that cancerous cells from patients with different leukaemia forms featured stable and strong expression of CD71, we designed a ferritin-based As nanomedicine, As@Fn, that bound to leukaemia cells with very high affinity, and efficiently delivered cytotoxic As-III into a large diversity of leukaemia cell lines and patient cells. Moreover, As@Fn exerted strong anti-leukaemia effects in diverse cell-line-derived xenograft models, as well as in a patient-derived xenograft model, in which it consistently outperformed the gold standard, showing its potential as a precision treatment for a variety of leukaemias. |
DOI | 10.1038/s41565-021-00980-7 |
Language | 英语 |
WOS Keyword | H-FERRITIN ; IN-VITRO ; T-CELLS ; TRIOXIDE ; NANOPARTICLES ; BINDING ; MAGNETOFERRITIN ; COMPLEXES ; RESISTANT ; ACID |
Funding Project | National Natural Science Foundation of China[U2001224] ; National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[21725301] ; National Natural Science Foundation of China[21821004] ; National Natural Science Foundation of China[51622211] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29040303] ; National Key R&D Program of China[2017YFA0207900] ; Open Funding Project of the State Key Laboratory of Biochemical Engineering[2012KF-03] ; Guangzhou Regenerative Medicine and Health Guangdong Laboratory[2018GZR110105014] ; Natural Science Foundation of Guangdong Province[2018B030311042] ; Beijing Outstanding Young Scientist Program[BJJWZYJH01201914430039] ; Tencent Foundation through the XPLORER PRIZE |
WOS Research Area | Science & Technology - Other Topics ; Materials Science |
WOS Subject | Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary |
Funding Organization | National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; Open Funding Project of the State Key Laboratory of Biochemical Engineering ; Guangzhou Regenerative Medicine and Health Guangdong Laboratory ; Natural Science Foundation of Guangdong Province ; Beijing Outstanding Young Scientist Program ; Tencent Foundation through the XPLORER PRIZE |
WOS ID | WOS:000710873000004 |
Publisher | NATURE PORTFOLIO |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ipe.ac.cn/handle/122111/50755 |
Collection | 中国科学院过程工程研究所 |
Corresponding Author | Li, Yuhua; Wei, Wei; Ma, Guanghui; Ma, Ding |
Affiliation | 1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing, Peoples R China 2.Univ Chinese Acad Sci, Sch Chem Engn, Beijing, Peoples R China 3.Peking Univ, Beijing Natl Lab Mol Engn, Coll Chem & Mol Engn, Beijing, Peoples R China 4.Peking Univ, Coll Engn, Beijing, Peoples R China 5.Peking Univ, BIC ESAT, Beijing, Peoples R China 6.Southern Med Univ, Zhujiang Hosp, Dept Hematol, Guangzhou, Peoples R China 7.Beijing Univ Chem Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn, Beijing, Peoples R China 8.Univ Chinese Acad Sci, Sch Phys Sci, Beijing, Peoples R China 9.Univ Chinese Acad Sci, CAS Key Lab Vacuum Sci, Beijing, Peoples R China 10.Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China |
Recommended Citation GB/T 7714 | Wang, Changlong,Zhang, Wei,He, Yanjie,et al. Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects[J]. NATURE NANOTECHNOLOGY,2021:17. |
APA | Wang, Changlong.,Zhang, Wei.,He, Yanjie.,Gao, Zirui.,Liu, Liyuan.,...&Ma, Ding.(2021).Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects.NATURE NANOTECHNOLOGY,17. |
MLA | Wang, Changlong,et al."Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects".NATURE NANOTECHNOLOGY (2021):17. |
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