Journal
NATURE NANOTECHNOLOGY
Volume 16, Issue 12, Pages 1413-U164Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41565-021-00980-7
Keywords
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Funding
- National Natural Science Foundation of China [U2001224, 21821005, 21725301, 21821004, 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
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Trivalent arsenic (As-III) is effective in treating acute promyelocytic leukemia, but its limitations include low effective concentrations in leukemia cells and off-target cytotoxicity. Researchers designed a ferritin-based As nanomedicine, As@Fn, that targets leukemia cells expressing CD71 with high affinity, demonstrating improved efficacy in different leukemia types in animal models.
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.
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