Red blood cell membrane-coated FLT3 inhibitor nanoparticles to enhance FLT3-ITD acute myeloid leukemia treatment

作     者：Jisheng Liu Junli Chen Xifeng Zhang Yin Wu Xin Qi Jie Wang Xiang Gao Jisheng Liu;Junli Chen;Xifeng Zhang;Yin Wu;Xin Qi;Jie Wang;Xiang Gao

作者机构：Department of Neurosurgery and Institute of NeurosurgeryState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China Department of HematologyWest China HospitalSichuan UniversityChengdu 610041China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2024年第35卷第9期

页      面：303-308页

核心收录：

学科分类：1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 0702[理学-物理学] 

基　　金：supported by the National Natural Science Foundation of China(No.32222046,China) the Sichuan Science and Technology Program(Nos.2022NSFSC0823,2023NSFSC193,2022NSFSC0793,China) the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21022,China) 

主　　题：FLT3-ITD Acute myeloid leukemia AML Red blood cell membrane Biomimetics 

摘      要：FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients,and are associated with unfavorable prognosis,higher risk of relapse,drug resistance,and poor clinical *** FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD *** is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule ***,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side *** we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML ***,we physically coextruded red blood cell(RBC)membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M,which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro,while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation ***,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free *** findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.