방사선의학 웹진

바로가기  >

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.

Author information

Hwang DW1, Kim HY2, Li F3, Park JY4, Kim D4, Park JH5, Han HS6, Byun JW4, Lee YS2, Jeong JM4, Char K7, Lee DS8.​

1 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.

2 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.

3 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.

4 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

5 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.

6 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Republic of Korea.

7 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.

8 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.