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

Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 462-474页

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 Institute of Immunology and Department of Orthopedics of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Henan Key Laboratory for Digestive Organ Transplantation the First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina Zhejiang University Cancer Centre HangzhouChina Department of Critical Care Medicine of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhouChina Department of Emergency Medicine Tongde Hospital of Zhejiang ProvinceHangzhouChina Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang Provincial Key Lab of OphthalmologyHangzhouChina 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 SciencesHangzhouChina

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 ***,fatal side effects greatly impede CAR T cell *** vesicles(EVs)are excellent carriers of therapeutic ***,EVs mainly accumulate in the liver when administered without *** an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B ***,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage *** 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 *** the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,***,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 ***,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

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