Nat Nanotechnol breakthrough!

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iNature trivalent arsenic (AsIII) is an effective drug for the treatment of patients with acute promyelocytic leukemia, but its ionic nature has caused several major limitations, such as low effective concentration in leukemia cells and high off-target cell toxicity, which limits Its general application in other types of leukemia
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On October 25, 2021, Ma Guanghui, Wei Wei, Martin of Peking University, and Yuhua Li of Southern Medical University from the Institute of Process Engineering of the Chinese Academy of Sciences published an online publication titled "Ferritin-based targeted delivery of arsenic to" in Nature Nanotechnology (IF=39).
Diverse leukaemia types confers strong anti-leukaemia therapeutic effects" research paper.
Based on clinical findings, cancer cells from different leukemia patients have stable and strong CD71 expression characteristics.
The study designed a ferritin-based As nano-drug As@Fn and As@Fn bind to leukemia cells with very high affinity, and effectively deliver cytotoxic AsIII to a large number of different leukemia cell lines and patient cells
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In addition, As@Fn has played a strong anti-leukemia effect in xenograft models derived from multiple cell lines and xenograft models derived from patients.
In this model, it has always been superior to the gold standard, showing that it can be used as an accurate treatment for various leukemias.
Potential
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Leukemia has always been a serious threat to human health, and the survival rate of adults and children is very low
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Due to its complex pathogenesis and characteristics, leukemia can be divided into many types according to the course of the disease (acute and chronic leukemia) and the source of leukemia cells (myeloid and lymphocytic leukemia)
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So far, chemotherapy is still the main clinical treatment method.
For different types of leukemia, many programs based on chemotherapy drugs and their combinations have been established
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Among these chemotherapy drugs, arsenic trioxide (ATO) is the first-line anti-tumor drug for the treatment of acute promyelocytic leukemia (APL), which is a subtype of acute myeloid leukemia (AML)
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As a medicinal form, trivalent arsenic (AsIII) can play an anti-leukemia effect mainly by inducing cell apoptosis
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However, ATO in clinical preparations is an ionic agent (ATO injection), which can be quickly eliminated in the body
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This off-target distribution always damages the therapeutic index and increases toxic side effects
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More seriously, the absorption efficiency of this ion AsIII in other types of leukemia cells may even be lower, thus limiting the application of anti-leukemia to other types of leukemia
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This dilemma emphasizes the urgent need to develop new strategies to effectively deliver AsIII to different leukemia types
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To achieve this goal, one possible method is to discover new targets for leukemia cells and construct corresponding AsIII vectors for delivery
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Although a series of new targets that are highly expressed on leukemia cells (such as CD19, CD20, and CD22) have been identified, their expression characteristics (such as abundance and stability) vary greatly among different types and courses of leukemia
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In terms of vector construction, nanoparticles should usually be synthesized for AsIII regulation, and target ligands (eg, antibodies, peptides) should be combined to bind leukemia cells
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Unfortunately, nanocarriers synthesized from exogenous materials always cause safety issues for clinical use, and the complex ligand binding process creates further obstacles for expansion of production and quality control
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In view of these considerations, the study found a reliable target here, and rationally designed a biomimetic AsIII nanocarrier using its ligand, which can be used to effectively treat a variety of leukemia types
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In short, clinical observations indicate that leukemia cells from patients with multiple types and courses of leukemia are often characterized by strong expression of CD71
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As a CD71 ligand, ferritin with unique quaternary structure, lumen and thermal stability is used to accommodate AsIII through a coordination process mediated by ferric iron
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The resulting As@Fn specifically binds to several types of leukemia cells with high affinity, thereby significantly increasing the uptake of AsIII and greatly enhancing cytotoxicity
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In the cell line-derived xenograft (CDX) model and the patient-derived xenograft (PDX) model, the study systematically verified that this strategy can show superior anti-leukemia efficacy than the combination of ATO and other chemotherapy
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The above results are still pre-clinical studies, and the actual clinical efficacy still needs to be further verified
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In view of the fact that Fn is a human endogenous component and ATO is an approved drug, the preparation has good clinical transformation potential
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 The corresponding authors of this paper are Prof.
Guanghui Ma (Institute of Process, Chinese Academy of Sciences), Prof.
Martin (Peking University), Prof.
Wei Wei (Institute of Process Research, Chinese Academy of Sciences), and Prof.
Li Yuhua (Zhujiang Hospital); the first author is PhD student Wang Changlong (Institute of Process, Chinese Academy of Sciences), Dr.
Zhang Wei (Peking University) and Deputy Chief Physician He Yanjie (Zhujiang Hospital)
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