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      Confined growth of ZIF-8 in dendritic mesoporous organosilica nanoparticles as bioregulators for enhanced mRNA delivery in vivo

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          Abstract

          Zeolitic imidazolate framework-8 (ZIF-8) and its composites have diverse applications. However, ZIF-8-based nanocomposites are mainly used as carriers in biomolecular delivery, with the functions of metal ions and ligands rarely used to modulate the biofunctions. In this work, dendritic mesoporous organosilica nanoparticles (DMONs) with tetrasulfide bond were used to confine ZIF-8 growth partially inside mesopores as a novel nanocomposite for mRNA delivery. Each component in the resultant DMONs-ZIF-8 contributed to mRNA delivery applications, including high loading benefitting from positively charged ZIF-8 and large mesopores of DMONs, endosomal escape promoted by the imidazole ring of ZIF-8, and long-term glutathione depletion mediated by both zinc ions and tetrasulfide bond. Combined together, DMONs-ZIF-8 demonstrated enhanced mRNA translation and better transfection efficiency than commercial products and toxic polymer-modified DMONs in vitro and in vivo.

          Abstract

          Confined growth of ZIF-8 nanocrystals in the large mesopores of organosilica nanoparticles with tetrasulfide bond is reported to upregulate mRNA translation and enhance delivery performance.

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          Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules

          Kang Liang, Raffaele Ricco, Cara M. Doherty … (2015)
          Enhancing the robustness of functional biomacromolecules is a critical challenge in biotechnology, which if addressed would enhance their use in pharmaceuticals, chemical processing and biostorage. Here we report a novel method, inspired by natural biomineralization processes, which provides unprecedented protection of biomacromolecules by encapsulating them within a class of porous materials termed metal-organic frameworks. We show that proteins, enzymes and DNA rapidly induce the formation of protective metal-organic framework coatings under physiological conditions by concentrating the framework building blocks and facilitating crystallization around the biomacromolecules. The resulting biocomposite is stable under conditions that would normally decompose many biological macromolecules. For example, urease and horseradish peroxidase protected within a metal-organic framework shell are found to retain bioactivity after being treated at 80 °C and boiled in dimethylformamide (153 °C), respectively. This rapid, low-cost biomimetic mineralization process gives rise to new possibilities for the exploitation of biomacromolecules.
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            A unifying model for mTORC1-mediated regulation of mRNA translation

            Carson C. Thoreen, Lynne Chantranupong, Heather R. Keys … (2012)
            The mTOR Complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses 1 . mTORC1 regulates mRNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in cells acutely treated with the mTOR inhibitor Torin1, which, unlike rapamycin, fully inhibits mTORC1 2 . These data reveal a surprisingly simple view of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5′ terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5′ UTR length or complexity 3 . mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown 4 . Remarkably, loss of just the well-characterized mTORC1 substrates, the 4E-BP family of translational repressors, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors.
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              Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation

              Lei Miao, Linxian X Li, Yuxuan Huang … (2019)
              Article 0 comments Cited 191 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yue Wang
                Hao Song
                Chao Liu
                Ye Zhang
                Yueqi Kong
                Jie Tang
                Yannan Yang
                Chengzhong Yu
                Journal
                Journal ID (nlm-ta): Natl Sci Rev
                Journal ID (iso-abbrev): Natl Sci Rev
                Journal ID (publisher-id): nsr
                Title: National Science Review
                Publisher: Oxford University Press
                ISSN (Print): 2095-5138
                ISSN (Electronic): 2053-714X
                Publication date Collection: August 2021
                Publication date (Electronic): 23 October 2020
                Publication date PMC-release: 23 October 2020
                Volume: 8
                Issue: 8
                Electronic Location Identifier: nwaa268
                Affiliations
                Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, QLD 4072, Australia
                Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, QLD 4072, Australia
                School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200241, China
                School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200241, China
                Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, QLD 4072, Australia
                Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, QLD 4072, Australia
                Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, QLD 4072, Australia
                Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, QLD 4072, Australia
                School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200241, China
                Author notes
                Corresponding author. E-mail: c.yu@ 123456uq.edu.au
                Article
                Publisher ID: nwaa268
                DOI: 10.1093/nsr/nwaa268
                PMC ID: 8363327
                PubMed ID: 34691708
                SO-VID: 4b6a31a1-5e1f-4cfb-84e0-e9cec98ba0e4
                Copyright © © The Author(s) 2020. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 01 February 2020
                Date revision received : 30 September 2020
                Date accepted : 13 October 2020
                Page count
                Pages: 10
                Funding
                Funded by: Australian Research Council, DOI 10.13039/501100000923;
                Award ID: DP200102962
                Categories
                Subject: Research Article
                Subject: Materials Science
                Subject: AcademicSubjects/MED00010
                Subject: AcademicSubjects/SCI00010

                Keywords: mesoporous organosilica nanoparticles,metal-organic framework,mrna transfection,cellular delivery,bioregulator
                Data availability:
                Keywords: mesoporous organosilica nanoparticles, metal-organic framework, mrna transfection, cellular delivery, bioregulator

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