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Novel Ferritin-Based Nanomedicine is Efficacious to Treat Diverse Human Leukemia

A novel ferritin (Fn)-based nanomedicine has been created by researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences, Peking University, and Zhujiang Hospital of Southern Medical University.

Novel Ferritin-Based Nanomedicine is Efficacious to Treat Diverse Human Leukemia

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The nanomedicine serves for the targeted delivery of arsenic (As) and has been shown to be an efficient therapy against various types of leukemia. The paper describing this technique was published in Nature Nanotechnology on October 25th, 2021.

Leukemia is a major threat to human health, presenting poor survival rates for adults and children alike. Clinically, chemotherapy is still the primary therapeutic modality for leukemia of diverse types, and it unavoidably leads to off-target distribution and harmful side effects.

When chemotherapeutic drugs are delivered in a targeted way to leukemia cells, harmful side effects can be avoided, and therapeutic effects can be enhanced. Although various new targets on leukemia cells have been determined, their expression features differ greatly for multiple types and courses of leukemia.

Researchers screened large numbers of clinical samples and confirmed that patients with various forms of leukemia presented stable and strong expression of CD71. Yuhua Li, a Professor at Zhujiang Hospital commented, "CD71 can be used as a new and reliable target for the development of anti-leukemia precision therapies."

Fn is the CD71 ligand with an exclusive quaternary structure and interior cavity, which are ideal for drug accommodation. A ferric-mediated coordination process helped efficient loading of trivalent As (AsIII), the medicinal form of the chemotherapeutic drug arsenic trioxide (ATO), inside Fn.

The loading content is ~200 As in each Fn and the As matches the known clinically efficacious valence state of the approved ATO.

Ding Ma, Professor, Peking University

The [email protected] formulation exhibited a robust capacity to attach to various types of leukemia cells. Following internalization, the AsIII would subsequently be released in the acidic lysosome.

We are excited to observe that our [email protected] nanomedicine significantly improved As accumulation in leukemia cells both in vitro and in vivo,” noted Prof. Wei Wei from IPE. “Such target behavior is favorable for improving the killing effect on leukemia cells while reducing the toxicity to normal tissues.”

When it comes to therapeutic efficacy, [email protected] outclassed the gold standard in various cell line-derived xenograft models, and also in a patient-derived xenograft model.

This nanomedicine not only expanded the therapeutic window of As but also extended the application to more types of leukemia. Given that Fn is an endogenous protein and ATO has been approved for clinical anti-leukemia use, our nanomedicine has the potential for clinical translation.

Guanghui Ma, Professor, Institute of Process Engineering, Chinese Academy of Sciences

According to a peer reviewer from Nature Nanotechnology, “Overall, the study was well conducted and controlled with substantial amount of in vitro and in vivo data to support that the newly developed [email protected] as a novel ferritin-based As nanomedicine is efficacious to treat diverse human leukemia.”

Journal Reference:

Wang, C., et al. (2021) Ferritin-based targeted delivery of arsenic to diverse leukemia types confers strong anti-leukemia therapeutic effects. Nature Nanotechnology. doi.org/10.1038/s41565-021-00980-7.

Source: https://english.cas.cn/

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