整合素α6靶向自组装促凋亡纳米多肽对中枢神经系统急性淋巴细胞白血病的靶向治疗  

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

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 

机构地区：[1]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 [2]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 [3]School of Pharmaceutical Sciences(Shenzhen),Shenzhen Campus of Sun Yat-sen University,Shenzhen 518107,China [4]Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering,Biomaterials Research Center,School of Biomedical Engineering,Southern Medical University,Guangzhou 510515,China [5]State Key Laboratory of Organ Failure Research,Guangdong Provincial Institute of Nephrology,Southern Medical University,Guangzhou 510515,China

出　　处：《Engineering》2024年第4期226-240,共15页工程（英文）

基　　金：supported by grants from the National Natural Science Foundation of China (81972531, 82373175, 82102775, and 82002466);the Major Scientific and Technological Projects of Guangdong Province (2019B020202002);the Young Talents Program of Sun Yat-sen University Cancer Center (YTP-SYSUCC-0067)

摘　　要：There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 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 integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-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.

关 键 词：Central nervous system acute lymphoblastic LEUKEMIA Integrinα6 Targeted peptide Proapoptotic Nanopeptide 

分 类 号：R739.4[医药卫生—肿瘤]