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Metal-organic frameworks nanoswitch: Toward photo-controllable endo/lysosomal rupture and release for enhanced cancer RNA interference

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Abstract

Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery. Herein, a novel photo-controllable metal-organic frameworks (MOFs) nanoswitch is rationally designed for enhancing small interfering RNA (siRNA) delivery. One single laser triggers the “off-to-on” switching of MOFs nanocomplexes, inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ ions, which cooperatively contribute to remarkable endo/lysosomal rupture (∼ 90%). The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer therapy. Notably, the “off-to-on” switching also activates fluorescence recovery for real-time monitoring siRNA delivery. The nanoswitch could easily be extended to deliver other therapeutic agents (e.g., DNA, protein, anticancer drug) for overcoming endo/lysosomal entrapment.

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Acknowledgements

We acknowledge Jingru Huang and Baoying Xie from Central Laboratory in School of Medicine, Xiamen University for assistance with inductively coupled plasma experiment, laser scanning confocal microscope and data analysis. This work was supported by the Major State Basic Research Development Program of China (No. 2017YFA0205201), the National Natural Science Foundation of China (Nos. 81925019, 81422023, U1705281, and U1505221), the Fundamental Research Funds for the Central Universities (No. 20720190088), and the Program for New Century Excellent Talents in University, China (No. NCET-13-0502). All animal experiments were approved by the Animal Management and Ethics Committee of the Xiamen University.

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Author notes

  1. Gan Lin, Yang Zhang, and Long Zhang contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China

    Gan Lin, Yang Zhang, Long Zhang, Junqing Wang, Ye Tian, Wen Cai, Shangui Tang, Chengchao Chu & Gang Liu

  2. The Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria, 3010, Australia

    Gan Lin

  3. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Singapore

    JiaJing Zhou

  4. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, 610041, China

    Peng Mi

  5. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA

    Xiaoyuan Chen

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  1. Gan Lin
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  2. Yang Zhang
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  3. Long Zhang
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Correspondence to Gang Liu.

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Metal-organic frameworks nanoswitch: Toward photo-controllable endo/lysosomal rupture and release for enhanced cancer RNA interference

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Lin, G., Zhang, Y., Zhang, L. et al. Metal-organic frameworks nanoswitch: Toward photo-controllable endo/lysosomal rupture and release for enhanced cancer RNA interference. Nano Res. 13, 238–245 (2020). https://doi.org/10.1007/s12274-019-2606-2

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  • DOI: https://doi.org/10.1007/s12274-019-2606-2

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