Journal
NANO RESEARCH
Volume 13, Issue 1, Pages 238-245Publisher
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-019-2606-2
Keywords
metal-organic frameworks; endo/lysosomal rupture and release; photo-controllable nanoswitch; RNA interference; cancer therapy
Categories
Funding
- Major State Basic Research Development Program of China [2017YFA0205201]
- National Natural Science Foundation of China [81925019, 81422023, U1705281, U1505221]
- Fundamental Research Funds for the Central Universities [20720190088]
- Program for New Century Excellent Talents in University, China [NCET-13-0502]
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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 (similar to 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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