title: A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.
abstract: Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here we show that exosomes, endogenous nano-sized membrane vesicles secreted by most cell types, can deliver chemotherapeutics such as doxorubicin (Dox) to tumor tissue in BALB/c nude mice. To reduce immunogenicity and toxicity, mouse immature dendritic cells (imDCs) were used for exosome production. Tumor targeting was facilitated by engineering the imDCs to express a well-characterized exosomal membrane protein (Lamp2b) fused to αv integrin-specific iRGD peptide (CRGDKGPDC). Purified exosomes from imDCs were loaded with Dox via electroporation, with an encapsulation efficiency of up to 20%. iRGD exosomes showed highly efficient targeting and Dox delivery to αv integrin-positive breast cancer cells in vitro as demonstrated by confocal imaging and flow cytometry. Intravenously injected targeted exosomes delivered Dox specifically to tumor tissues, leading to inhibition of tumor growth without overt toxicity. Our results suggest that exosomes modified by targeting ligands can be used therapeutically for the delivery of Dox to tumors, thus having great potential value for clinical applications.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China; College of Pharmaceutical Science, Jilin University, Changchun 130021, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Tian
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Ji
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors.forename: Motao
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.affiliation: College of Pharmaceutical Science, Jilin University, Changchun 130021, China. Electronic address: jingyanweijlu@163.com.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Wei
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China. Electronic address: niegj@nanoctr.cn.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D001483:Base Sequence; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004587:Electrophoresis, Agar Gel; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D009369:Neoplasms / Q000188:drug therapy*; D009838:Oligodeoxyribonucleotides
chemical_list: D000903:Antibiotics, Antineoplastic; D009838:Oligodeoxyribonucleotides; D004317:Doxorubicin
keywords: Doxorubicin; Exosome; Tumor therapy; iRGD; αv Integrin-positive cancer cells