•  
  •  
 
Nano Research

Article Title

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

Authors

Gan Lin, 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
Yang Zhang, 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
Long Zhang, 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
Junqing Wang, 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
Ye Tian, 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
Wen Cai, 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
Shangui Tang, 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
Chengchao Chu, 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
JiaJing Zhou, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457, Singapore
Peng Mi, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China
Xiaoyuan Chen, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
Gang Liu, 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

Keywords

metal-organic frameworks, endo/lysosomal rupture and release, photo-controllable nanoswitch, RNA interference, cancer therapy

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.

Graphical Abstract

Publisher

Tsinghua University Press

Share

COinS