RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21.
Autor: | Lee TJ; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Yoo JY; Department of Neurological Surgery, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Shu D; Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA., Li H; Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA., Zhang J; Department of Biomedical Informatics, Center for Biostatistics, Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH 43210, USA., Yu JG; Department of Otolaryngology, Head & Neck Surgery, The Ohio State University Medical Center, Columbus, OH 43210, USA., Jaime-Ramirez AC; Department of Neurological Surgery, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Acunzo M; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Romano G; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Cui R; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Sun HL; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Luo Z; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Old M; Department of Otolaryngology, Head & Neck Surgery, The Ohio State University Medical Center, Columbus, OH 43210, USA., Kaur B; Department of Neurological Surgery, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA., Guo P; Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: guo.1091@osu.edu., Croce CM; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. Electronic address: carlo.croce@osumc.edu. |
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Jazyk: | angličtina |
Zdroj: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2017 Jul 05; Vol. 25 (7), pp. 1544-1555. Date of Electronic Publication: 2017 Jan 18. |
DOI: | 10.1016/j.ymthe.2016.11.016 |
Abstrakt: | Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma. Here, we report that multi-valent folate (FA)-conjugated 3WJ RNP constructed to harbor anti-miR-21 LNA sequences (FA-3WJ-LNA-miR21) specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution. Systemically injected FA-3WJ-LNA-miR21 RNP efficiently rescued PTEN and PDCD4, resulting in glioblastoma cell apoptosis and tumor growth regression. Overall survival rate was also significantly improved by FA-3WJ-LNA-miR21 RNP. These results are indicative of the clinical benefit of FA-3WJ RNP-based gene therapy for the successful targeted therapy of developing and even recurring glioblastoma. (Copyright © 2016. Published by Elsevier Inc.) |
Databáze: | MEDLINE |
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