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

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外文摘要：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 diag-nosis 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 inte-grin 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.

外文关键词：

Central nervous system acute lymphoblasticleukemiaIntegrin α6Targeted peptideProapoptoticNanopeptide

作者：

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

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作者单位：

Guangdong Provincial Key Laboratory of New Drug Screening & NMPA Key Laboratory of Drug Metabolism Research and Evaluation,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China

State Key Laboratory of Oncology in South China & Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,China

School of Pharmaceutical Sciences(Shenzhen),Shenzhen Campus of Sun Yat-sen University,Shenzhen 518107,China

Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering,Biomaterials Research Center,School of Biomedical Engineering,Southern Medical University,Guangzhou 510515,China

State Key Laboratory of Organ Failure Research,Guangdong Provincial Institute of Nephrology,Southern Medical University,Guangzhou 510515,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaMajor Scientific and Technological Projects of Guangdong ProvinceYoung Talents Program of Sun Yatsen University Cancer CenterResearch Data Deposit(RDD)public platform

项目编号：

819725318237317582102775820024662019B020202002YTP-SYSUCC-0067RDDB2023462053

出版年：

2024

DOI：

10.1016/j.eng.2023.11.012

工程(英文)

CSTPCDEI

ISSN：2095-8099

年,卷(期)：2024.35(4)