title: The Promising Nanocarrier for Doxorubicin and siRNA Co-delivery by PDMAEMA-based Amphiphilic Nanomicelles.
abstract: Synergistic effects of anticancer drug and siRNA have displayed superior advantages for cancer therapy. Herein, we deeply analyzed the feasibility that whether doxorubicin (DOX) and siRNA could be co-delivered by mPEG-PCL-graft-PDMAEMA (PECD) micelles, which mediated excellent DNA/siRNA delivery in vitro and in vivo reported in our previous work. DOX-loaded NPs (PECD-D) were developed by nanoprecipitation technology and exhibited high drug loading content (DLC, 9.5%). In vitro cytotoxicity study in MDA-MB-231 cells, PECD-D treated groups had lower IC50 compared to free DOX groups (F-DOX) at different transfection time (24, 48, and 72h), which maybe attribute to its high cellular uptake and endosomal escape properties. The speculation was confirmed with the results of drug release profile in acidic media, flow cytometry analysis and confocal images. Futhermore, Cy5 labeled siRNA was introduced in PECD-D micelles (PECD-D/siRNA) to track the behavior of dual-loaded nanodrug in vitro and in vivo. Flow cytometry analysis presented that DOX and siRNA were successfully co-delivered into cells, the positive cells ratio were 94.6 and 99.5%, respectively. Confocal images showed that not only DOX and siRNA existed in cytoplasm, but DOX traversed endosome/lysosome and entered into cell nucleus. For in vivo tumor-targeting evaluation in BALB/c nude mice, both DOX and Cy5-siRNA could be detected in tumor sites after intravenous injection with PECD-D/siRNA formulation. Therefore, we believed that PECD micelles have a potential ability as DOX and siRNA co-delivery carrier for cancer therapy.
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Lingwei
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
authors.forename: Shangcong
authors.initials: S
authors.lastname: Han
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, China.
authors.forename: Tuo
authors.initials: T
authors.lastname: Wei
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Xinyun
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Shuquan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Yuanyu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, China.
authors.forename: Xing-jie
authors.initials: XJ
authors.lastname: Liang
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300072, China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300072, China.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; D004317:Doxorubicin
keywords: PDMAEMA; co-delivery; doxorubicin; nanodrug; siRNA