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Construction of a target MSNs drugcarrier loaded with siRNAGLI1 and siRNASMO aim at hedgehog signal pathway and the pharmacodynamic study of drug-carriers in the treatment of leukemia stem cells

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Abstract

Leukemia stem cells (LSCs) are responsible for leukemia initiation and targeting LSCs is one strategy to treat this disease. This study aims to target LSCs using multi-siRNA loaded antibodies modified with mesoporous silica nanoparticles (MSNs). Here, both siRNAGLI1 and siRNASMO were loaded in an anti-CD34 antibody modified with MSNs, and then, the MSN@siRNAGLI1@Antibody + MSNs@siRNASMO@Antibody cocktail was used to target LSCs. Expression levels of BCL-2 in LSCs were significantly reduced whereas Bax expression was significantly increased after treatment with nano-drug carriers. In addition, these nano-drug carriers also effectively induced the apoptosis of LSCs. The MSNs@siRNAGLI1@Antibody + MSNs@siRNASMO@Antibody cocktail significantly inhibited LSCs. In short, we constructed two target MSN nano-drug carriers where loaded siRNAs can be used in a chemotherapeutic drug cocktail to improve the treatment of leukemia.

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The work described has not been submitted elsewhere for publication and thereby not under simultaneous consideration by another journal.

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Funding

This work was supported by the National Natural Science Foundation of China (NO.81802429).

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Authors and Affiliations

  1. Key Clinical Laboratory of Henan Province, Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Yuan Zhang, HaiJun Li, Yu Duan, Yan Zhang, Wei Jing, ShaoGang Lv, Xi Chu, Zheng Cao & Liang Ming

  2. Zhengzhou No.7 People’s Hospital, Zhengzhou, 450016, Henan, China

    Rui Cai

  3. Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Lei Yang

Authors
  1. Yuan Zhang
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  2. Rui Cai
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  3. HaiJun Li
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  4. Yu Duan
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  5. Yan Zhang
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  6. Wei Jing
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  7. ShaoGang Lv
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  8. Xi Chu
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  9. Zheng Cao
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  10. Lei Yang
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  11. Liang Ming
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Contributions

Yuan Zhang: Conceptualization, Methodology, Experimental operation, Writing and Reviewing; Rui Cai, HaiJun Li, Yu Duan, Yan Zhang, Wei Jing, ShaoGang Lv, Xi Chu, Zheng Cao and Lei Yang plays equally to the Methodology, Experimental operation and Writing. Liang Ming was the mentor of the manuscript concept.

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Correspondence to Liang Ming.

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Zhang, Y., Cai, R., Li, H. et al. Construction of a target MSNs drugcarrier loaded with siRNAGLI1 and siRNASMO aim at hedgehog signal pathway and the pharmacodynamic study of drug-carriers in the treatment of leukemia stem cells. Drug Deliv. and Transl. Res. 12, 2463–2473 (2022). https://doi.org/10.1007/s13346-020-00893-3

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  • DOI: https://doi.org/10.1007/s13346-020-00893-3

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