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Leukemia is a hematological malignant tumor that seriously endangers human health.
The mortality rate among children and adults under 35 years old ranks first among malignant tumors
.
Currently, chemotherapy is still an important method for the treatment of leukemia.
The main clinical drugs include alkylating agents, antimetabolites, alkaloids, and arsenic (arsenic trioxide, ATO) proposed by Chinese scholars to treat cancer
.
For various types of leukemia, different standard chemotherapy regimens have been established clinically, but the overall treatment effect still needs to be improved
.
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, researcher Ma Guanghui, Researcher Wei Wei, Professor of the State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Professor Martin from the School of Chemistry and Molecular Engineering of Peking University, and Professor Li Yuhua from Zhujiang Hospital of Southern Medical University teamed up in Nature.
A research paper entitled: Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects was published on Nanotechnology
.
The study found that a variety of leukemia cells have specific and high expression of CD71 broad-spectrum characteristics.
It is proposed to use CD71 ligand ferritin particles (Fn) as a drug carrier to solve the problem of efficiently loading Fn with the leukemia treatment drug arsenic trioxide (ATO) and realize Targeted delivery significantly inhibits the progression of a variety of leukemias
.
The State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, based on ferritin particles (Fn) and the approved drug arsenic trioxide (ATO) in the body, proposed a new biomimetic delivery strategy and cooperated with Peking University and Zhujiang Hospital.
Facing the actual needs of clinical applications, the research and development of innovative preparations for leukemia targeted therapy has been carried out
.
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%)
.
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
.
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.
Based on this, the research team proposed to use CD71 ligand Fn as a carrier to target ATO to improve the therapeutic effect and reduce side effects
.
However, the internal cavity of Fn is very limited (diameter ~ 8 nm), which poses a challenge for the efficient loading and controlled release of small molecule ATO
.
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)
.
After intravenous injection, arsenic-based ferritin (As@Fn) can be identified by CD71 to target and accumulate in leukemia cells, and selectively release active trivalent arsenic in intracellular acid lysosomes, effectively killing leukemia cells
.
The above-mentioned biomimetic targeted delivery strategy has significantly improved the tolerated dose of clinical arsenic preparations, and expanded the indications from acute promyelocytic leukemia to acute myeloid, acute lymphocytic and chronic myeloid leukemia types
.
The research team proved on clinical samples and patient-derived xenograft models that As@Fn 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
.
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.
The research team stated that the above results are still clinical In previous studies, the actual clinical efficacy still needs to be further verified
.
In view of the fact that Fn is a human endogenous component and ATO is an approved drug, the preparation has good clinical transformation potential
.
The research team is cooperating to advance the follow-up R&D and transformation in accordance with relevant requirements
.
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
.
Dr.
Changlong Wang (Institute of Process Engineering, Chinese Academy of Sciences), Dr.
Wei Zhang (Peking University), and Deputy Chief Physician He Yanjie (Zhujiang Hospital) are the co-first authors of the paper
.
Researcher Ma Guanghui (Institute of Process Engineering), Professor Martin (Peking University), Researcher Wei Wei (Institute of Process Engineering), and Professor Li Yuhua (Zhujiang Hospital) are the co-corresponding authors
.
Related work has been supported by the National Natural Science Foundation of China, the National Key R&D Program Project, the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences, and the Guangzhou Regenerative Medicine and Health Guangdong Laboratory Project
.
Link to the paper: https:// Hot Article Selection in 2020 1.
The cup is ready! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight and restored the old brain to a young state.
.
.
The mortality rate among children and adults under 35 years old ranks first among malignant tumors
.
Currently, chemotherapy is still an important method for the treatment of leukemia.
The main clinical drugs include alkylating agents, antimetabolites, alkaloids, and arsenic (arsenic trioxide, ATO) proposed by Chinese scholars to treat cancer
.
For various types of leukemia, different standard chemotherapy regimens have been established clinically, but the overall treatment effect still needs to be improved
.
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, researcher Ma Guanghui, Researcher Wei Wei, Professor of the State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Professor Martin from the School of Chemistry and Molecular Engineering of Peking University, and Professor Li Yuhua from Zhujiang Hospital of Southern Medical University teamed up in Nature.
A research paper entitled: Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects was published on Nanotechnology
.
The study found that a variety of leukemia cells have specific and high expression of CD71 broad-spectrum characteristics.
It is proposed to use CD71 ligand ferritin particles (Fn) as a drug carrier to solve the problem of efficiently loading Fn with the leukemia treatment drug arsenic trioxide (ATO) and realize Targeted delivery significantly inhibits the progression of a variety of leukemias
.
The State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, based on ferritin particles (Fn) and the approved drug arsenic trioxide (ATO) in the body, proposed a new biomimetic delivery strategy and cooperated with Peking University and Zhujiang Hospital.
Facing the actual needs of clinical applications, the research and development of innovative preparations for leukemia targeted therapy has been carried out
.
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%)
.
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
.
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.
Based on this, the research team proposed to use CD71 ligand Fn as a carrier to target ATO to improve the therapeutic effect and reduce side effects
.
However, the internal cavity of Fn is very limited (diameter ~ 8 nm), which poses a challenge for the efficient loading and controlled release of small molecule ATO
.
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)
.
After intravenous injection, arsenic-based ferritin (As@Fn) can be identified by CD71 to target and accumulate in leukemia cells, and selectively release active trivalent arsenic in intracellular acid lysosomes, effectively killing leukemia cells
.
The above-mentioned biomimetic targeted delivery strategy has significantly improved the tolerated dose of clinical arsenic preparations, and expanded the indications from acute promyelocytic leukemia to acute myeloid, acute lymphocytic and chronic myeloid leukemia types
.
The research team proved on clinical samples and patient-derived xenograft models that As@Fn 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
.
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.
The research team stated that the above results are still clinical In previous studies, the actual clinical efficacy still needs to be further verified
.
In view of the fact that Fn is a human endogenous component and ATO is an approved drug, the preparation has good clinical transformation potential
.
The research team is cooperating to advance the follow-up R&D and transformation in accordance with relevant requirements
.
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
.
Dr.
Changlong Wang (Institute of Process Engineering, Chinese Academy of Sciences), Dr.
Wei Zhang (Peking University), and Deputy Chief Physician He Yanjie (Zhujiang Hospital) are the co-first authors of the paper
.
Researcher Ma Guanghui (Institute of Process Engineering), Professor Martin (Peking University), Researcher Wei Wei (Institute of Process Engineering), and Professor Li Yuhua (Zhujiang Hospital) are the co-corresponding authors
.
Related work has been supported by the National Natural Science Foundation of China, the National Key R&D Program Project, the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences, and the Guangzhou Regenerative Medicine and Health Guangdong Laboratory Project
.
Link to the paper: https:// Hot Article Selection in 2020 1.
The cup is ready! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight and restored the old brain to a young state.
.
.
