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Research Article

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

Gan Lin1,2,§, Yang Zhang1,§, Long Zhang1,§, Junqing Wang1, Ye Tian1, Wen Cai1, Shangui Tang1, Chengchao Chu1, JiaJing Zhou3, Peng Mi4, Xiaoyuan Chen5, Gang Liu1( )
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
The Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457, Singapore
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA

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

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Graphical Abstract

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.

Keywords

metal-organic frameworksendo/lysosomal rupture and releasephoto-controllable nanoswitchRNA interferencecancer therapy

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Nano Research
Volume 13 Issue 1,
January 2020
Pages 238-245
DOI: 10.1007/s12274-019-2606-2
Cite this article:
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 Research, 2020, 13(1): 238-245. https://doi.org/10.1007/s12274-019-2606-2
Topics:
DiseasesGene transferGenesOncologyOrganometallicsRNATargeted drug delivery

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Received: 09 September 2019
Revised: 09 December 2019
Accepted: 15 December 2019
Published: 03 January 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
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