Nat Nanotech: Chinese scholars have developed a highly efficient bionic delivery vehicle loaded with arsenic, which can significantly inhibit a variety of leukemias

Leukemia is a hematological malignant tumor that seriously endangers human health.

The creation of drug carriers based on natural particles in the body can target the delivery of drugs through the inherent pathways in the body, overcome the complex environment and multiple barriers in the body, improve the efficacy of approved drugs and expand the indications, and have high druggability

On October 25, 2021, a team of Prof.

Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects

The study found that a variety of leukemia cells have specific and high expression of CD71 broad-spectrum characteristics.

The State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, based on the natural components of ferritin particles (Fn) in the body and the approved drug arsenic trioxide (ATO), proposed a new strategy for biomimetic delivery, and cooperated with Peking University and Zhujiang Hospital.

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 leukemia cells in patient samples The expression level of CD71 was significantly increased (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 vivo

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 vivo Figure 1: CD71 expression of leukemia cells, construction and targeting analysis of As@Fn: (a) The positive rate of CD71 expression in each cell group in the bone marrow of leukemia patients; (b) ) Proportion of each cell population; (c) C71 expression abundance of each cell population; (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) As@Fn and ATO leukemia cell endocytosis comparison; (i) As@Fn intracellular localization; (j) As@Fn and ATO for leukemia cells IC50 comparison; (k) As@Fn in vivo targeted leukemia cell analysis; (l) As@Fn and ATO in vivo distribution comparison

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

Based on the heat resistance of Fn, the affinity of iron to the inner cavity of Fn, and the interaction between arsenic and iron, the research team cleverly designed iron pre-nucleation strategies and efficiently anchored trivalent arsenic (Fn:As=1: 200)

The above-mentioned biomimetic targeted delivery strategy significantly improves the tolerated dose of clinical arsenic preparations, and extends the indications from acute promyelocytic leukemia to acute myeloid, acute lymphocytic and chronic myeloid leukemia types

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

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 Figure 2: As@Fn in the source of patients Curative effect on 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) Weight change curve of mice in different treatment groups; (d) Different treatments Proportion of leukemia cells in peripheral blood (PB), bone marrow (BM) and spleen of mice in the group; (e) Survival curves of mice in different treatment groups

The research team stated that the above results are still pre-clinical studies, and the actual clinical efficacy still needs to be further verified

The research is based on the previous research foundation, and after 11 years of painstaking research and cross-cooperation, the research team has developed another targeted delivery formulation with transformative potential based on the new leukemia target

Original source:

Original source:

Wang, C.

Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects.


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