Targeted Therapy of Central Nervous System Acute Lymphoblastic Leukemia with an Integrin α6-Targeted Self-Assembling Proapoptotic Nanopeptide

Jia-Cong Ye, Wan-Qiong Li, Mei-Ling Chen, Qian-Kun Shi, Hua Wang, Xin-Ling Li, Ying-He Li, Jie Yang, Qiao-Li Wang, Fang Hu, Yan-Feng Gao, Shu-Wen Liu, Mu-Sheng Zeng, Guo-Kai Feng

Engineering ›› 2024, Vol. 35 ›› Issue (4) : 226-240.

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Engineering ›› 2024, Vol. 35 ›› Issue (4) : 226-240. DOI: 10.1016/j.eng.2023.11.012
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Targeted Therapy of Central Nervous System Acute Lymphoblastic Leukemia with an Integrin α6-Targeted Self-Assembling Proapoptotic Nanopeptide

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Abstract

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia (CNS-ALL). Integrin α6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression. The targeted peptide D(RWYD) (abbreviated RD), with nanomolar affinity to integrin α6 was identified by peptide scanning techniques such as alanine scanning, truncation, and D-substitution. Herein, we developed a therapeutic nanoparticle based on the integrin α6-targeted peptide for treating CNS-ALL. The self-assembled proapoptotic nanopeptide D(RWYD)-D(KLAKLAK)2-GD(FFY) (abbreviated RD-KLA-Gffy) contains the integrin α6-targeted peptide RD, the well-known proapoptotic peptide D(KLAKLAK)2 (abbreviated KLA), and the self-assembling tetrapeptide GD(FFY) (abbreviated Gffy). The functional mechanism of RD-KLA-Gffy is clarified using different experiments. Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis, thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity. Moreover, the combined use of RD-KLA-Gffy and methotrexate (MTX) shows a potent antitumor effect in treating CNS-ALL, indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX, which shows promise for application in CNS-ALL therapy.

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Central nervous system acute lymphoblastic leukemia / Integrin α6 / Targeted peptide / Proapoptotic / Nanopeptide

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Jia-Cong Ye, Wan-Qiong Li, Mei-Ling Chen, Qian-Kun Shi, Hua Wang, Xin-Ling Li, Ying-He Li, Jie Yang, Qiao-Li Wang, Fang Hu, Yan-Feng Gao, Shu-Wen Liu, Mu-Sheng Zeng, Guo-Kai Feng. Targeted Therapy of Central Nervous System Acute Lymphoblastic Leukemia with an Integrin α6-Targeted Self-Assembling Proapoptotic Nanopeptide. Engineering, 2024, 35(4): 226‒240 https://doi.org/10.1016/j.eng.2023.11.012

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