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      Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers

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          Abstract

          Single-strand oligonucleotides provide promising potential as new therapeutics towards various diseases. However, the efficient delivery of oligonucleotide therapeutics is still challenging due to their susceptibility to nuclease degradation and the lack of effective carriers for condensation. In this study, we reported the use of natural polyphenol to facilitate the condensation of single-strand oligonucleotides by cationic polymers. Green tea catechin complexed with single-strand oligonucleotides to form anionic nanoparticles, which were further coated by low molecular weight cationic polymers to increase their cell internalization. The resulting core-shell structured nanoparticles, so-called green nanoparticles (GNPs), showed improved cargo stability, and achieved high efficiency in the delivery of several types of single-strand oligonucleotides including antisense oligonucleotides, anti-miRNA, and DNAzyme. This study provides a facile strategy for the efficient delivery of single-strand oligonucleotides.

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          Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies.

          Alex R D Delbridge, Stephanie Grabow, Andreas Strasser … (2016)
          The 'hallmarks of cancer' are generally accepted as a set of genetic and epigenetic alterations that a normal cell must accrue to transform into a fully malignant cancer. It follows that therapies designed to counter these alterations might be effective as anti-cancer strategies. Over the past 30 years, research on the BCL-2-regulated apoptotic pathway has led to the development of small-molecule compounds, known as 'BH3-mimetics', that bind to pro-survival BCL-2 proteins to directly activate apoptosis of malignant cells. This Timeline article focuses on the discovery and study of BCL-2, the wider BCL-2 protein family and, specifically, its roles in cancer development and therapy.
          Article 0 comments Cited 315 times – based on 0 reviews     Review now
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            MicroRNA silencing for cancer therapy targeted to the tumor microenvironment

            Christopher J Cheng, Raman Bahal, Imran A Babar … (2015)
            SUMMARY PARAGRAPH MicroRNAs (miRNAs) are short non-coding RNAs expressed in different tissue and cell types that suppress the expression of target genes. As such, miRNAs are critical cogs in numerous biological processes 1,2 , and dysregulated miRNA expression is correlated with many human diseases. Certain miRNAs, called oncomiRs, play a causal role in the onset and maintenance of cancer when overexpressed. Tumors that depend on these miRNAs are said to display oncomiR addiction 3–5 . Some of the most effective anticancer therapies target oncogenes like EGFR and HER2; similarly, inhibition of oncomiRs using antisense oligomers (i.e. antimiRs) is an evolving therapeutic strategy 6,7 . However, the in vivo efficacy of current antimiR technologies is hindered by physiological and cellular barriers to delivery into targeted cells 8 . Here we introduce a novel antimiR delivery platform that targets the acidic tumor microenvironment, evades systemic clearance by the liver, and facilitates cell entry via a non-endocytic pathway. We found that the attachment of peptide nucleic acid (PNA) antimiRs to a peptide with a low pH-induced transmembrane structure (pHLIP) produced a novel construct that could target the tumor microenvironment, transport antimiRs across plasma membranes under acidic conditions such as those found in solid tumors (pH ~6), and effectively inhibit the miR-155 oncomiR in a mouse model of lymphoma. This study introduces a new paradigm in the use of antimiRs as anti-cancer drugs, which can have broad impacts on the field of targeted drug delivery.
            Article 0 comments Cited 313 times – based on 0 reviews     Review now
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              Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma.

              Frank J Slack, Christopher J Cheng, X Liang … (2012)
              MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these "addicted" pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.
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                Author and article information

                Contributors
                Yiwen Li: ywli@scu.edu.cn
                Yiyun Cheng: yycheng@mail.ustc.edu.cn
                Journal
                Journal ID (nlm-ta): Gene Ther
                Journal ID (iso-abbrev): Gene Ther
                Title: Gene Therapy
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 0969-7128
                ISSN (Electronic): 1476-5462
                Publication date (Electronic): 4 May 2020
                Publication date PMC-release: 4 May 2020
                Publication date (Print): 2020
                Volume: 27
                Issue: 7
                Pages: 383-391
                Affiliations
                [1 ]GRID grid.22069.3f, ISNI 0000 0004 0369 6365, Shanghai Key Laboratory of Regulatory Biology, , East China Normal University, ; Shanghai, 200241 China
                [2 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, , Sichuan University, ; Chengdu, 610065 China
                [3 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, , South China University of Technology, ; Guangzhou, 510640 China
                Article
                Publisher ID: 151
                DOI: 10.1038/s41434-020-0151-y
                PMC ID: 7445782
                PubMed ID: 32366887
                SO-VID: b86fc8d6-ac6a-458f-b958-468035c1c6d8
                Copyright © © The Author(s) 2020
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 16 January 2020
                Date revision received : 24 March 2020
                Date accepted : 8 April 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 21725402
                Award ID: 21774079
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100003399, Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission);
                Award ID: 17XD1401600
                Award ID: 188014580
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100012541, Guangdong Innovative and Entrepreneurial Research Team Program;
                Award ID: 2016ZT06C322
                Award Recipient :
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © Springer Nature Limited 2020

                ScienceOpen disciplines: Molecular medicine
                Keywords: gene delivery,gene therapy
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: gene delivery, gene therapy

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