Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia  

作　　者：Yifeng Xia Jingnan An Jiaying Li Wenxing Gu Yifan Zhang Songsong Zhao Cenzhu Zhao Yang Xu Bin Li Zhiyuan Zhong Fenghua Meng 

机构地区：[1]Biomedical Polymers Laboratory,College of Chemistry,Chemical Engineering and Materials Science,and State Key Laboratory of Radiation Medicine and Protection,Soochow University,Suzhou,215123,PR China [2]College of Pharmaceutical Sciences,Soochow University,Suzhou,215123,PR China [3]Jiangsu Institute of Hematology,The First Affiliated Hospital of Soochow University,Institute of Blood and Marrow Transplantation of Soochow University,Collaborative Innovation Center of Hematology,Soochow University,Suzhou,215123,PR China [4]Orthopedic Institute,Soochow University,Suzhou,215007,PR China

出　　处：《Bioactive Materials》2023年第3期499-510,共12页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(NSFC 52033006 and 82000157);Natural Science Foundation of Jiangsu Province(NO.BK20190173).

摘　　要：Acute myeloid leukemia(AML)remains a most lethal hematological malignancy,partly because of its slow development of targeted therapies compared with other cancers.PLK1 inhibitor,volasertib(Vol),is among the few molecular targeted drugs granted breakthrough therapy status for AML;however,its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits.Here,we report that transferrin-guided polymersomes(TPs)markedly augment the targetability,potency and safety of Vol to AML.Vol-loaded TPs(TPVol)with 4%trans-ferrin exhibited best cellular uptake,effective down-regulation of p-PLK1,p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells.Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow.The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood,bone marrow,liver and spleen,effectively enhanced mouse survival rate,and impeded bone loss.This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.

关 键 词：Targeted delivery Acute myeloid leukemia Polo-like kinase 1 Molecular targeted drug 

分 类 号：R733.7[医药卫生—肿瘤]