Researchers at the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences, Peking University and the Zhujiang Hospital of Southern Medical University have a ferritin (Fn) -based nanomedicine for the targeted release of arsenic (As) and for efficient therapy against various leukemias develops types.

The study was published in Nature Nanotechnology on October 25th.

Leukemia is a serious threat to human health, with poor survival rates for both adults and children. In the clinic, chemotherapy is still the most important therapeutic method for all types of leukemia and inevitably leads to a maldistribution and toxic side effects.

The targeted delivery of chemotherapeutic agents to leukemia cells can alleviate toxic side effects and intensify the therapeutic effects. Several new targets have been identified on leukemia cells, but their expression characteristics vary widely for different types and courses of leukemia.

By screening a large number of clinical samples, the researchers confirmed that patients with various forms of leukemia had stable and high levels of expression of CD71. “CD71 can be used as a new and reliable target for the development of precision therapies for leukemia,” said Prof. LI Yuhua of Zhujiang Hospital.

As a CD71 ligand, Fn has a unique quaternary structure and internal cavity that are beneficial for drug accommodation. With the help of an iron-mediated coordination process, trivalent As (AsIII), the drug form of the chemotherapeutic agent arsenic trioxide (ATO), was efficiently loaded into Fn.

“The charge level is ~ 200 As in each Fn and the As corresponds to the known clinically effective valence state of the approved ATO,” said Prof. MA Ding of Peking University.

the [email protected] The formulation retained a strong ability to bind to various types of leukemia cells. After internalization, the AsIII would then be released in the acidic lysosome.

“We are happy that our [email protected] Nanomedicine significantly improved Enrichment in leukemia cells both in vitro and in vivo, “said Prof. WEI Wei from the IPE.” Such target behavior is beneficial in order to improve the killing effect on leukemia cells and at the same time reduce the toxicity for normal tissue. “

As for the therapeutic effectiveness, [email protected] Exceeded the gold standard in various xenograft models derived from cell lines as well as in a patient-derived xenograft model.

“This nanomedicine has not only expanded the therapeutic window of As, but also extended its application to other types of leukemia,” said Prof. MA Guanghui from the IPE. “Because Fn is an endogenous protein and ATO has been approved for clinical use in leukemia, our nanomedicine has the potential for clinical implementation.”

A peer reviewer from Nature Nanotechnology said, “Overall, the study was well conducted and controlled, with a significant amount of in vitro and in vivo data to show that the newly developed” [email protected] as a novel ferritin-based As nanomedicine is effective in treating various human leukemias. “

Source:

Headquarters of the Chinese Academy of Sciences

Journal reference:

Wang, C., et al. (2021) The targeted delivery of ferritin-based arsenic to various types of leukemia confers strong therapeutic effects against leukemia. Nature nanotechnology. doi.org/10.1038/s41565-021-00980-7.

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