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Leukemia is a hematological malignant tumor that seriously harms human health.
Chemotherapy is still an important means of clinical treatment.
The main drugs include alkylating agents, antimetabolites, alkaloids, and arsenic trioxide (ATO) proposed by Chinese scholars
.
For various types of leukemia, different standard chemotherapy regimens have been established clinically, but the efficacy still needs to be improved
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 was significantly increased (average positive rate>90%)
.
The specific high expression of CD71 is not limited to the type and process of leukemia, which proves its feasibility as a broad-spectrum target of leukemia cells
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 (Figure 1)
.
Based on the heat resistance of Fn, the affinity of iron to the Fn cavity, and the interaction between arsenic and iron, the research team cleverly designed a strategy for iron pre-nucleation, and efficiently anchored trivalent arsenic in the Fn cavity (Fn: As=1: 200)
This research provides new theories and technologies for targeted delivery therapy of leukemia through cross-cooperative innovation of materials, chemistry, chemical engineering, medicine and other multidisciplinary
Figure 1 Create a leukemia targeted delivery and treatment system based on Fn and ATO: (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 abundance of each cell group C71; ( d) As@Fn transmission electron microscope image; (e) As@Fn energy spectrum; (f) As@Fn spherical aberration electron microscope image; (g) As@Fn in vivo targeted leukemia cell analysis; (h) As@Fn and Comparison of the distribution of ATO in vivo; (i) the white blood cell change curve of leukemia PDX model mice after different treatment schemes; (j) the survival curve of mice in different treatment groups
