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%)
Figure 1: Leukemia cell CD71 expression, As@Fn construction and targeting analysis: (a) The positive rate of CD71 expression in each cell group in the bone marrow of leukemia patients; (b) The proportion of each cell group; (c) The expression of C71 in each cell group Abundance; (d) As@Fn transmission electron microscope image; (e) As@Fn energy spectrum image; (f) As@Fn spherical aberration electron microscope image; (g) As@Fn and leukemia cell specific binding curve; (h ) Comparison of the endocytosis of As@Fn and ATO in leukemia cells; (i) Intracellular localization of As@Fn; (j) Comparison of IC50 of As@Fn and ATO for leukemia cells; (k) As@Fn targeting leukemia cells in vivo Analysis; (l) Comparison of the distribution of As@Fn and ATO in the body (photo courtesy of the research team)
Figure 1: Leukemia cell CD71 expression, As@Fn construction and targeting analysis: (a) The positive rate of CD71 expression in each cell group in the bone marrow of leukemia patients; (b) The proportion of each cell group; (c) The expression of C71 in each cell group Abundance; (d) As@Fn transmission electron microscope image; (e) As@Fn energy spectrum image; (f) As@Fn spherical aberration electron microscope image; (g) As@Fn and leukemia cell specific binding curve; (h ) Comparison of the endocytosis of As@Fn and ATO in leukemia cells; (i) Intracellular localization of As@Fn; (j) Comparison of IC50 of As@Fn and ATO for leukemia cells; (k) As@Fn targeting leukemia cells in vivo Analysis; (l) Comparison of the distribution of As@Fn and ATO in the body (photo courtesy of the research team) 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
Figure 2: The curative effect of As@Fn on the patient-derived leukemia xenotransplantation model: (a) Leukemia PDX model construction and pharmacodynamic analysis diagram; (b) White blood cell change curve of mice in different treatment groups; (c) mice in different treatment groups Body weight change curve; (d) the proportion of leukemia cells in peripheral blood (PB), bone marrow (BM) and spleen of mice in different treatment groups; (e) survival curve of mice in different treatment groups (photo courtesy of the research team)
Figure 2: The curative effect of As@Fn on the patient-derived leukemia xenotransplantation model: (a) Leukemia PDX model construction and pharmacodynamic analysis diagram; (b) White blood cell change curve of mice in different treatment groups; (c) mice in different treatment groups Body weight change curve; (d) the proportion of leukemia cells in peripheral blood (PB), bone marrow (BM) and spleen of mice in different treatment groups; (e) survival curve of mice in different treatment groups (photo courtesy of the research team) 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.
In this paper, corresponding author for the Chinese Academy of Sciences researcher Ma Guanghui Process Engineering, Peking University professor Martin Peking University, Chinese Academy of Sciences Process Engineering researcher Professor Wei Weihe Zhujiang Hospital, Li Yuhua; the first author to Chinese Academy of Sciences Dr.
Chinese Academy of SciencesChinese Academy of Sciences ChineseAcademy of Sciences Chinese Academy ofSciencesChineseAcademy of Sciences Chinese Academy ofSciences Chinese Academy of SciencesChinese Academy of Sciences ChineseAcademy of Sciences Chinese Academy ofSciences Related paper information: https://doi.
https://doi.
org/10.
1038//s41565-021-00980-7 https://doi.
org/10.
1038//s41565-021-00980-7
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