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 

机构地区：[1]Department of Neurosurgery and Institute of Neurosurgery,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,West China Medical School,Sichuan University,Chengdu 610041,China [2]West China School of Basic Medical Sciences&Forensic Medicine,Sichuan University,Chengdu 610041,China [3]Department of Hematology,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Chinese Chemical Letters》2024年第9期303-308,共6页中国化学快报（英文版）

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).

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 outcome.Even FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD mutations.This is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule inhibitors.Besides,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side effects.Here we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML treatment.Briefly,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 properties.Furthermore,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free drug.These 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.

关 键 词：FLT3-ITD Acute myeloid leukemia AML Red blood cell membrane Biomimetics 

分 类 号：R733.71[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]