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Leukemia is a kind of malignant tumor that makes people "disguised", commonly known as "blood cancer"
In order to improve its therapeutic effect and expand its indications, Ma Guanghui and Wei Wei, researchers at the State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, proposed a new strategy of "bionic delivery", and joined forces with Peking University professor Martin and Southern Medical University Professor Li Yuhua of Zhujiang Hospital has carried out close cooperation, using natural ferritin particles (Fn) present in the body as a drug carrier to solve the problem of Fn efficiently loading ATO and achieve targeted delivery, significantly inhibiting the progression of a variety of leukemias
The research paper will be published in Nature Nanotechnology at 23:00, October 25, 2021, Beijing time
The principle of biomimetic delivery is to create a drug carrier based on natural particles in the body, and to target the delivery of drugs by means of an inherent path in the body
The research team first collected a large number of clinical peripheral blood and bone marrow samples, and found that the CD71 expression levels of red blood cells, lymphocytes, monocytes and granulocytes in healthy samples were low (average positive rate <10%), while the leukemia cells in patient samples The expression level of cd71 increased significantly (average positive rate>90%)
On this basis, the research team proposed to use CD71 ligand Fn as a carrier to target ATO to improve the therapeutic effect and reduce side effects
According to reports, during the research process, since the diameter of the Fn cavity is less than 8 nanometers, the space is very limited, which poses a challenge to the efficient loading and controllable release of small molecule ATO
Experiments show that after intravenous injection, arsenic-based ferritin can be identified by CD71, targeted to enrich leukemia cells, and selectively release active trivalent arsenic in intracellular acid lysosomes, effectively killing leukemia cells
Researchers believe that this means that the above-mentioned biomimetic targeted delivery strategy has significantly improved the tolerated dose of clinical arsenic preparations and expanded the indications to acute myeloid, acute lymphocytic and chronic myeloid leukemia types
At the same time, the research team proved in clinical samples and patient-derived xenograft models that arsenic-based ferritin can significantly inhibit the progression of a variety of leukemias, and the effect is significantly better than the existing single ATO and combined chemotherapy strategies
According to the researchers, the above results are still pre-clinical studies, and the actual clinical efficacy still needs to be further verified
It is reported that for more than ten years, Ma Guanghui and Wei Wei’s team have discovered and created a series of new drug and vaccine delivery dosage forms, which have been successfully used in the prevention and treatment of tumors, infectious diseases, and inflammatory diseases in animal models, and some of the dosage forms have passed the hospital.
The corresponding authors of this paper are Ma Guanghui, a researcher at the Institute of Process Engineering, Chinese Academy of Sciences, Martin, a professor at Peking University, Wei Wei, a researcher at the Institute of Process Engineering, Chinese Academy of Sciences, and Li Yuhua, a professor at Zhujiang Hospital; He Yanjie, deputy chief physician of Zhujiang Hospital
Related paper information:
https://doi.