This trojan horse strategy improves arsenic uptake, outperforming the current gold standard.
As of 2018, leukaemia is the top ten leading cause of cancer death in China. Leukaemia is a cancer of the white blood cells, where abnormal white blood cells responsible for fighting infections, block up the bone marrow and impairs its ability to produce red blood cells and platelets. Currently, chemotherapy is still the main therapeutic approach for the different types of leukaemia though it inevitably causes off-target distribution and toxic side effects. This calls for a need to design new methods to effectively transport chemotherapeutic drugs to the various leukaemia types.
To do this, scientists can construct specific carriers for targeted delivery, which can reduce toxic side effects and increase therapeutic effects. While a handful of new targets have been identified on leukaemia cells, their expression features differ greatly for various types and courses of leukaemia.
In a study published in Nature Nanotechnology, a team from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences, Peking University, and Zhujiang Hospital of Southern Medical University have designed a ferritin (Fn)-based nanomedicine for targeted delivery of arsenic, thereby improving arsenic uptake and providing more effective therapy for various leukaemia types.
By screening large numbers of clinical samples, the researchers observed that patients with different types and courses of leukaemia exhibited stable and strong expression of receptor CD71. “CD71 can be used as a new and reliable target for the development of anti-leukaemia precision therapies,” said Professor Li Yuhua of Zhujiang Hospital.
As a ligand of CD71, Fn’s unique quaternary structure and interior cavity made it ideal for drug accommodation. With the assistance of a ferric-mediated coordination process, trivalent arsenic, which is the medicinal form of the chemotherapeutic drug arsenic trioxide, was effectively loaded inside Fn.
“The loading content is ~200 [arsenic] in each [ferritin] and the [arsenic] matches the known clinically efficacious valence state of the approved [arsenic trioxide],” said Professor Ma Ding of Peking University.
The obtained [email protected] formulation maintained the ability to bind to different types of leukaemia cells with high affinity, leading to improved arsenic uptake and enhanced cytotoxicity.
“We are excited to observe that our [email protected] nanomedicine significantly improved [arsenic] accumulation in leukaemia cells both in vitro and in vivo,” said Professor Wei wei from IPE. “Such target behaviour is favourable for improving the killing effect on leukaemia cells while reducing the toxicity to normal tissues.”
When compared to the gold standard in diverse cell line-derived xenograft models and patient-derived xenograft models, the [email protected] displayed much superior anti-leukaemia effects.
“This nanomedicine not only expanded the therapeutic window of [arsenic] but also extended the application to more types of leukaemia,” said Professor Ma Guanghui from IPE. “Given that [ferritin] is an endogenous protein and [arsenic trioxide] has been approved for clinical anti-leukaemia use, our nanomedicine has the potential for clinical translation.” [APBN]
Source: Wang et al. (2021). Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects. Nature Nanotechnology, 1-11