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

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 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

作者机构：Guangdong Provincial Key Laboratory of New Drug Screening&NMPA Key Laboratory of Drug Metabolism Research and EvaluationSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Oncology in South China&Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences(Shenzhen)Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue EngineeringBiomaterials Research CenterSchool of Biomedical EngineeringSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologySouthern Medical UniversityGuangzhou 510515China 

出 版 物：《Engineering》 (工程（英文）)

年 卷 期：2024年第35卷第4期

页      面：226-240页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0703[理学-化学] 100214[医学-肿瘤学] 10[医学] 

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) 

主　　题：Central nervous system acute lymphoblastic leukemia Integrinα6 Targeted peptide Proapoptotic Nanopeptide 

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 *** targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and ***,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating *** 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 *** 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 ***,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.