title: Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy.
abstract: Oncolytic viruses have been utilized for the treatment of various cancers. However, delivery of the viral particles to tumor cells remains a major challenge. Microparticles (MP) are vesicle forms of plasma membrane fragments of 0.1-1 μm in size that are shed by cells. We have previously shown the delivery of chemotherapeutic drugs using tumor cell-derived MPs (T-MP). Here we report that T-MPs can be utilized as a unique carrier system to deliver oncolytic adenoviruses to human tumors, leading to highly efficient cytolysis of tumor cells needed for in vivo treatment efficacy. This T-MP-mediated oncolytic virotherapy approach holds multiple advantages, including: 1) delivery of oncolytic adenovirus by T-MPs is able to avoid the antiviral effect of host antibodies; 2) delivery of oncolytic adenovirus by T-MPs is not limited by virus-specific receptor that mediates the entry of virus into tumor cells; 3) T-MPs are apt at delivering oncolytic adenoviruses to the nucleus of tumor cells as well as to stem-like tumor-repopulating cells for the desired purpose of killing them. These findings highlight a novel oncolytic adenovirus delivery system with highly promising clinical applications.
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ran
authors.affiliation: Center Laboratory, Beijing Military General Hospital of PLA, Beijing, 100700, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tan
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Ji
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Dong
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Tong
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Degao
authors.initials: D
authors.lastname: Chen
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Yin
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Molecular Immunology and Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215123, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qin
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China; Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China. Electronic address: tjhuangbo@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics*
chemical_list: D004337:Drug Carriers
keywords: Cancer therapy; Delivery system; Microparticles; Oncolytic adenovirus