Researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences, Peking University and Zhujiang Hospital of Southern Medical University have developed a ferritin (Fn)-based nanomedicine for targeted delivery of arsenic (As) and efficient therapy against diverse leukaemia types.

The study was published in Nature Nanotechnology.

Leukaemia is a severe threat to human health, with poor survival rates for both adults and children. In the clinic, chemotherapy is still the main therapeutic modality for all types of leukaemia and inevitably induces off-target distribution and toxic side effects.

Targeted delivery of chemotherapeutic drugs to leukaemia cells can relieve toxic side effects and enhance therapeutic effects. Several new targets have been identified on leukaemia cells, but their expression features vary greatly for different types and courses of leukaemia.

Through screening large numbers of clinical samples, researchers confirmed that patients with different forms of leukaemia featured stable and strong expression of CD71.

"CD71 can be used as a new and reliable target for the development of anti-leukaemia precision therapies," said Prof. LI Yuhua of Zhujiang Hospital.

As the CD71 ligand, Fn has a unique quaternary structure and interior cavity, which are favourable for drug accommodation. With the assistance of a ferric-mediated coordination process, trivalent As (AsIII), the medicinal form of the chemotherapeutic drug arsenic trioxide (ATO), was efficiently loaded 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," said Prof. MA Ding of Peking University.

The As@Fn formulation retained a strong capacity to bind to diverse types of leukaemia cells. After internalisation, the AsIII would then be released in the acidic lysosome.

"We are excited to observe that our As@Fn nanomedicine significantly improved As accumulation in leukaemia cells both in vitro and in vivo," said Prof. WEI Wei from IPE.

"Such target behaviour is favourable for improving the killing effect on leukaemia cells while reducing the toxicity to normal tissues."

In terms of therapeutic efficacy, As@Fn outperformed the gold standard in diverse cell line-derived xenograft models, as well as 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 leukaemia," said Prof. MA Guanghui from IPE.

"Given that Fn is an endogenous protein and ATO has been approved for clinical anti-leukaemia use, our nanomedicine has the potential for clinical translation."

A peer reviewer from Nature Nanotechnology said, "Overall, the study was well conducted and controlled with substantial amount of in vitro and in vivo data to support that the newly developed As@Fn as a novel ferritin-based As nanomedicine is efficacious to treat diverse human leukaemia."

Source: Chinese Academy of Sciences Headquarters