title: Functional exosome-mimic for delivery of siRNA to cancer: in vitro and in vivo evaluation.
abstract: Exosomes, the smallest subgroup of extracellular vesicles, have been recognized as extracellular organelles that contain genetic and proteomic information for long distance intercellular communication. Exosome-based drug delivery is currently a subject of intensive research. Here, we report a novel strategy to produce nanoscale exosome-mimics (EMs) in sufficient quantity for gene delivery in cancer both in vitro and in vivo. Size-controllable EMs were generated at a high yield by serial extrusion of non-tumorigenic epithelial MCF-10A cells through filters with different pore sizes. siRNA was then encapsulated into the EMs by electroporation. Biosafety and uptake efficiency of the EMs were evaluated both in vitro and in vivo. The mechanism underlying their cellular endocytosis was also studied.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43212, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43212, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Kang
authors.affiliation: Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43212, USA.
authors.forename: Chiling
authors.initials: C
authors.lastname: Chiang
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tumor Biomarker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China; Peking Union Medical College, Beijing 100021, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Tairong
authors.initials: T
authors.lastname: Kuang
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Aili
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43212, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China. Electronic address: tenglesheng@jlu.edu.cn.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA. Electronic address: lee.31@osu.edu.
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D018274:Electroporation; D004705:Endocytosis / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D055354:Exosomes; D018014:Gene Transfer Techniques; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering
keywords: Electroporation; Endocytosis; Exosome; MCF-7; siRNA