Journal Home > Volume 13 , Issue 1

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.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

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

Show Author's information Gan Lin1,2,§Yang Zhang1,§Long Zhang1,§Junqing Wang1Ye Tian1Wen Cai1Shangui Tang1Chengchao Chu1JiaJing Zhou3Peng Mi4Xiaoyuan Chen5Gang 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.

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

References(33)

[1]
Mintzer, M. A.; Simanek, E. E. Nonviral vectors for gene delivery. Chem. Rev. 2009, 109, 259-302.
[2]
Lächelt, U.; Wagner, E. Nucleic acid therapeutics using polyplexes: A journey of 50 years (and beyond). Chem. Rev. 2015, 115, 11043-11078.
[3]
Wang, J. Q.; Mi, P.; Lin, G.; Wáng, Y. X. J.; Liu, G.; Chen, X. Y. Imaging-guided delivery of RNAi for anticancer treatment. Adv. Drug Deliv. Rev. 2016, 104, 44-60.
[4]
Whitehead, K. A.; Langer, R.; Anderson, D. G. Knocking down barriers: Advances in siRNA delivery. Nat. Rev. Drug Discov. 2009, 8, 129-138.
[5]
Varkouhi, A. K.; Scholte, M.; Storm, G.; Haisma, H. J. Endosomal escape pathways for delivery of biologicals. J. Control. Release 2011, 151, 220-228.
[6]
Ma, D. Enhancing endosomal escape for nanoparticle mediated siRNA delivery. Nanoscale 2014, 6, 6415-6425.
[7]
Dominska, M.; Dykxhoorn, D. M. Breaking down the barriers: siRNA delivery and endosome escape. J. Cell Sci. 2010, 123, 1183-1189.
[8]
Gilleron, J.; Querbes, W.; Zeigerer, A.; Borodovsky, A.; Marsico, G.; Schubert, U.; Manygoats, K.; Seifert, S.; Andree, C.; Stöter, M. et al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 2013, 31, 638-646.
[9]
Shi, J. J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer 2016, 17, 20-37.
[10]
Shim, M. S.; Kwon, Y. J. Controlled delivery of plasmid DNA and siRNA to intracellular targets using ketalized polyethylenimine. Biomacromolecules 2008, 9, 444-455.
[11]
Shim, M. S.; Kwon, Y. J. Acid-responsive linear polyethylenimine for efficient, specific, and biocompatible siRNA delivery. Bioconjugate Chem. 2009, 20, 488-499.
[12]
Lin, G.; Zhu, W. C.; Yang, L.; Wu, J.; Lin, B. B.; Xu, Y.; Cheng, Z. Z.; Xia, C. C.; Gong, Q. Y.; Song, B. et al. Delivery of siRNA by MRI-visible nanovehicles to overcome drug resistance in MCF-7/ADR human breast cancer cells. Biomaterials 2014, 35, 9495-9507.
[13]
Hunter, A. C. Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity. Adv. Drug Deliv. Rev. 2006, 58, 1523-1531.
[14]
Chen, H. B.; Xiao, L.; Anraku, Y.; Mi, P.; Liu, X. Y.; Cabral, H.; Inoue, A.; Nomoto, T.; Kishimura, A.; Nishiyama, N. et al. Polyion complex vesicles for photoinduced intracellular delivery of amphiphilic photosensitizer. J. Am. Chem. Soc. 2014, 136, 157-163.
[15]
Yuan, Y. Y.; Zhang, C. J.; Liu, B. A photoactivatable AIE polymer for light-controlled gene delivery: Concurrent Endo/Lysosomal escape and DNA unpacking. Angew. Chem., Int. Ed. 2015, 54, 11419-11423.
[16]
Kim, J.; Kim, J.; Jeong, C.; Kim, W. J. Synergistic nanomedicine by combined gene and photothermal therapy. Adv. Drug Deliv. Rev. 2016, 98, 99-112.
[17]
Lin, G.; Mi, P.; Chu, C. C.; Zhang, J.; Liu, G. Inorganic nanocarriers overcoming multidrug resistance for cancer theranostics. Adv. Sci. 2016, 3, 1600134.
[18]
Feng, L. Z.; Yang, X. Z.; Shi, X. Z.; Tan, X. F.; Peng, R.; Wang, J.; Liu, Z. Polyethylene glycol and polyethylenimine dual-functionalized nano-graphene oxide for photothermally enhanced gene delivery. Small 2013, 9, 1989-1997.
[19]
Wang, H. M.; Zhong, L.; Liu, Y.; Xu, X.; Xing, C.; Wang, M.; Bai, S. M.; Lu, C. H.; Yang, H. H. A black phosphorus nanosheet-based siRNA delivery system for synergistic photothermal and gene therapy. Chem. Commun. 2018, 54, 3142-3145.
[20]
Wang, H.; Agarwal, P.; Zhao, S. T.; Yu, J. H.; Lu, X. B.; He, X. M. A near-infrared laser-activated “nanobomb” for breaking the barriers to microRNA delivery. Adv. Mat. 2016, 28, 347-355.
[21]
Midoux, P.; Pichon, C.; Yaouanc, J. J.; Jaffrès, P. A. Chemical vectors for gene delivery: A current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers. Br. J. Pharmacol. 2009, 157, 166-178.
[22]
Mishra, S.; Heidel, J. D.; Webster, P.; Davis, M. E. Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes. J. Control. Release 2006, 116, 179-191.
[23]
Sun, C. Y.; Qin, C.; Wang, X. L.; Yang, G. S.; Shao, K. Z.; Lan, Y. Q.; Su, Z. M.; Huang, P.; Wang, C. G.; Wang, E. B. Zeolitic imidazolate framework-8 as efficient pH-sensitive drug delivery vehicle. Dalton Trans. 2012, 41, 6906-6909.
[24]
Zhuang, J.; Kuo, C. H.; Chou, L. Y.; Liu, D. Y.; Weerapana, E.; Tsung, C. K. Optimized metal-organic-framework nanospheres for drug delivery: Evaluation of small-molecule encapsulation. ACS Nano 2014, 8, 2812-2819.
[25]
Alsaiari, S. K.; Patil, S.; Alyami, M.; Alamoudi, K. O.; Aleisa, F. A.; Merzaban, J. S.; Li, M.; Khashab, N. M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. J. Am. Chem. Soc. 2018, 140, 143-146.
[26]
Bus, T.; Traeger, A.; Schubert, U. S. The great escape: How cationic polyplexes overcome the endosomal barrier. J. Mater. Chem. B 2018, 6, 6904-6918.
[27]
Chu, C. C.; Ren, E.; Zhang, Y. M.; Yu, J. W.; Lin, H. R.; Pang, X.; Zhang, Y.; Liu, H.; Qin, Z. N.; Cheng, Y. et al. Zinc(II)-dipicolylamine coordination nanotheranostics: Toward synergistic nanomedicine by combined photo/gene therapy. Angew. Chem., Int. Ed. 2019, 58, 269-272.
[28]
Altieri, D. C. Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer 2008, 8, 61-70.
[29]
Park, D. H.; Cho, J.; Kwon, O. J.; Yun, C. O.; Choy, J. H. Biodegradable inorganic nanovector: Passive versus active tumor targeting in siRNA transportation. Angew. Chem., Int. Ed. 2016, 55, 4582-4586.
[30]
Lin, G.; Zhang, Y.; Zhu, C. Q.; Chu, C. C.; Shi, Y. S.; Pang, X.; Ren, E.; Wu, Y.Y.; Mi, P.; Xia, H. P. et al. Photo-excitable hybrid nanocomposites for image-guided photo/TRAIL synergistic cancer therapy. Biomaterials 2018, 176, 60-70.
[31]
Mi, P.; Cabral, H.; Kataoka, K. Ligand-installed nanocarriers toward precision therapy. Adv. Mat. 2019, 1902604.
[32]
Chen, T. T.; Yi, J. T.; Zhao, Y. Y.; Chu, X. Biomineralized metal-organic framework nanoparticles enable intracellular delivery and Endo-Lysosomal release of native active proteins. J. Am. Chem. Soc. 2018, 140, 9912-9920.
[33]
Li, S. D.; Huang, L. Targeted delivery of antisense oigodeoxynucleotide and small interference RNA into lung cancer cells. Mol. Pharm. 2006, 3, 579-588.
File
12274_2019_2606_MOESM1_ESM.pdf (3.1 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 09 September 2019
Revised: 09 December 2019
Accepted: 15 December 2019
Published: 03 January 2020
Issue date: January 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

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.

Return