Gp350-anchored extracellular vesicles: promising vehicles for delivering therapeutic drugs of B cell malignancies  

作　　者：Huiqing Xiu Xi Nan Danfeng Guo JiaoliWang Jiahui Li Yanmei Peng Guirun Xiong Shibo Wang Changjun Wang Gensheng Zhang Yunshan Yang Zhijian Cai 

机构地区：[1]Institute of Immunology,and Department of Orthopedics of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [2]Henan Key Laboratory for Digestive Organ Transplantation,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,China [3]Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Affiliated Hangzhou First People’s Hospital,Zhejiang University School of Medicine,Hangzhou,China [4]Zhejiang University Cancer Centre,Hangzhou,China [5]Department of Critical Care Medicine of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [6]Department of Emergency Medicine,Tongde Hospital of Zhejiang Province,Hangzhou,China [7]Second Affiliated Hospital of Zhejiang University School of Medicine,Zhejiang Provincial Key Lab of Ophthalmology,Hangzhou,China [8]Department of Medical Oncology,The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer(IBMC),Chinese Academy of Sciences,Hangzhou,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第3期462-474,共13页亚洲药物制剂科学（英文）

基　　金：supported by the Natural Science Foundation of Zhejiang Province(LY19H160009 and LY20H120007);the National Natural Science Foundation of China(82130053,81971871,31970845 and 81901571);the Joint Preresearch Fund for Clinical Scientific Research of Hangzhou First People’s Hospital Affiliated to Zhejiang University(YYJJ2019Z07);the Major Project of Hangzhou Health Science and Technology Plan(Z20200134).

摘　　要：Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.

关 键 词：Extracellular vesicles GP350 CD21 Red blood cells B cell malignancies 

分 类 号：R943[医药卫生—药剂学]