Ferritin-based nanomedicine developed for targeted leukemia therapy

As the CD71 ligand, Fn has a unique quaternary structure and interior cavity, which are favorable 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 leukemia cells. After internalization, 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 leukemia cells both in vitro and in vivo," said 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."

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 leukemia," said Prof. MA Guanghui from IPE. "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."

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 leukemia."