Anti-tumor Activity of miniPEG-γ-Modified PNAs to Inhibit MicroRNA-210 for Cancer Therapy.

Autor:	Gupta A; Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA., Quijano E; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA., Liu Y; Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA., Bahal R; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA., Scanlon SE; Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA., Song E; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA., Hsieh WC; Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Carnegie Mellon University, Pittsburgh, PA 15213, USA., Braddock DE; Department of Pathology, Yale University, New Haven, CT 06510, USA., Ly DH; Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Carnegie Mellon University, Pittsburgh, PA 15213, USA., Saltzman WM; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA., Glazer PM; Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA; Department of Genetics, Yale University, New Haven, CT 06510, USA. Electronic address: peter.glazer@yale.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2017 Dec 15; Vol. 9, pp. 111-119. Date of Electronic Publication: 2017 Sep 12.
DOI:	10.1016/j.omtn.2017.09.001
Abstrakt:	MicroRNAs (miRs) are frequently overexpressed in human cancers. In particular, miR-210 is induced in hypoxic cells and acts to orchestrate the adaptation of tumor cells to hypoxia. Silencing oncogenic miRs such as miR-210 may therefore offer a promising approach to anticancer therapy. We have developed a miR-210 inhibition strategy based on a new class of conformationally preorganized antisense γ peptide nucleic acids (γPNAs) that possess vastly superior RNA-binding affinity, improved solubility, and favorable biocompatibility. For cellular delivery, we encapsulated the γPNAs in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Our results show that γPNAs targeting miR-210 cause significant delay in growth of a human tumor xenograft in mice compared to conventional PNAs. Further, histopathological analyses show considerable necrosis, fibrosis, and reduced cell proliferation in γPNA-treated tumors compared to controls. Overall, our work provides a chemical framework for a novel anti-miR therapeutic approach using γPNAs that should facilitate rational design of agents to potently inhibit oncogenic microRNAs. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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