title: In vivo visualization of endogenous miR-21 using hyaluronic acid-coated graphene oxide for targeted cancer therapy.
abstract: Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously. Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes loaded onto HA-GO (HGP21) specifically targeted CD44-positive MBA-MB231 cells and showed fluorescence recovery by interacting with endogenous miR-21 in the cytoplasm of the MBA-MB231 cells. Knockdown of endogenous miR-21 by HGP21 led to decreased proliferation and reduced migration of cancer cells, as well as the induction of apoptosis, with enhanced PTEN levels. Interestingly, in vivo fluorescence signals markedly recovered 3 h after the intravenous delivery of HGP21 and displayed signals more than 5-fold higher than those observed in the HGPscr-treated group of tumor-bearing mice. These findings demonstrate the possibility of using the HGP nanoplatform as a cancer theranostic tool in miRNA-targeted therapy.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Medical Research Center, Institute of Radiation Medicine, Seoul National University College of Medicine, Republic of Korea; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Do Won
authors.initials: DW
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea.
authors.forename: Han Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: The National Creative Research Initiative Center for Intelligent Hybrids, School of Chemical & Biological Engineering, WCU Program of Chemical Convergence for Energy & Environment, Seoul National University, Republic of Korea; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Republic of Korea.
authors.forename: Hwa Seung
authors.initials: HS
authors.lastname: Han
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Byun
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea.
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: The National Creative Research Initiative Center for Intelligent Hybrids, School of Chemical & Biological Engineering, WCU Program of Chemical Convergence for Energy & Environment, Seoul National University, Republic of Korea. Electronic address: khchar@snu.ac.kr.
authors.forename: Kookheon
authors.initials: K
authors.lastname: Char
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea. Electronic address: dsl@snu.ac.kr.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000818:Animals; D006108:Graphite / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D010087:Oxides / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D053769:Nanocapsules; D010087:Oxides; D020135:Peptide Nucleic Acids; D006108:Graphite; D006820:Hyaluronic Acid
keywords: Cancer theranostics; Graphene oxide (GO); Hyaluronic acid (HA); MicroRNA knockdown; Optical imaging; Peptide nucleic acid (PNA); miR-21