Exo/endogenous factors co-activatable nanodevice for spatiotem-porally controlled miRNA imaging and guided tumor ablation
),
Download citation
569
Views
44
Downloads
12
Crossref
9
WoS
8
Scopus
1
CSCD
Remote activation of biomarker sensing holds a great promise of shifting the success of in vitro diagnostics to spatiotemporally controlled in vivo visualization of tumor, and in turn, imaging guided therapy. Herein, a "dual-key-one-lock" nanodevice was designed and built by assembling thermo-activatable probe of trimeric DNA hybrids into a mesoporous polydopamine nanoparticle-based multifunctional nanotransducer (probe host, fluorescence quencher, and photothermal conversion agent), enabling precisely switchable theranostic operations under the co-activation of exo/endogenous stimulations (near-infrared (NIR) light and microRNA (miRNA)). By this design, the NIR irradiation-induced local heat through the porous nanotransducer can be transferred to the DNA nanothermometer for triggering the exposure of the miRNA recognition segment, as well as the subsequent fluorescence activation by strand displacement reactions (SDR). A programmable application of short- (3 min) and long-duration (10 min) NIR irradiation was administered sequentially to induce a milder and a stronger hyperthermia, respectively, to activate the localized miRNA imaging, and in turn, tumor thermoablation under the fluorescence guidance in vivo. By reducing nonspecific activation, dual factor co-activatable nanodevices exhibited a high tumor-to-background ratio (TBR) value of 8.9, as well as a significantly lower (6–9-fold) normal tissue fluorescence as compared with those sensing miRNA solely. The in vivo results show that the tumors were significantly suppressed after the photothermal therapy with the assistance of the accurate miRNA diagnosis. This rationally integrated nanoplatform may pave a new avenue for advanced theranostic systems with high spatiotemporal precision by activatable designs.
menu
Exo/endogenous factors co-activatable nanodevice for spatiotem-porally controlled miRNA imaging and guided tumor ablation
),
Abstract
Remote activation of biomarker sensing holds a great promise of shifting the success of in vitro diagnostics to spatiotemporally controlled in vivo visualization of tumor, and in turn, imaging guided therapy. Herein, a "dual-key-one-lock" nanodevice was designed and built by assembling thermo-activatable probe of trimeric DNA hybrids into a mesoporous polydopamine nanoparticle-based multifunctional nanotransducer (probe host, fluorescence quencher, and photothermal conversion agent), enabling precisely switchable theranostic operations under the co-activation of exo/endogenous stimulations (near-infrared (NIR) light and microRNA (miRNA)). By this design, the NIR irradiation-induced local heat through the porous nanotransducer can be transferred to the DNA nanothermometer for triggering the exposure of the miRNA recognition segment, as well as the subsequent fluorescence activation by strand displacement reactions (SDR). A programmable application of short- (3 min) and long-duration (10 min) NIR irradiation was administered sequentially to induce a milder and a stronger hyperthermia, respectively, to activate the localized miRNA imaging, and in turn, tumor thermoablation under the fluorescence guidance in vivo. By reducing nonspecific activation, dual factor co-activatable nanodevices exhibited a high tumor-to-background ratio (TBR) value of 8.9, as well as a significantly lower (6–9-fold) normal tissue fluorescence as compared with those sensing miRNA solely. The in vivo results show that the tumors were significantly suppressed after the photothermal therapy with the assistance of the accurate miRNA diagnosis. This rationally integrated nanoplatform may pave a new avenue for advanced theranostic systems with high spatiotemporal precision by activatable designs.
References(55)
Hernot, S.; van Manen, L.; Debie, P.; Mieog, J. S. D.; Vahrmeijer, A. L. Latest developments in molecular tracers for fluorescence image-guided cancer surgery. Lancet Oncol. 2019, 20, e354–e367.
Gao, M.; Yu, F. B.; Lv, C. J.; Choo, J.; Chen, L. X. Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy. Chem. Soc. Rev. 2017, 46, 2237–2271.
Singh, H.; Tiwari, K.; Tiwari, R.; Pramanik, S. K.; Das, A. Small molecule as fluorescent probes for monitoring intracellular enzymatic transformations. Chem. Rev. 2019, 119, 11718–11760.
Li, J. J.; Cheng, F. F.; Huang, H. P.; Li, L. L.; Zhu, J. J. Nanomaterial- based activatable imaging probes: From design to biological applications. Chem. Soc. Rev. 2015, 44, 7855–7880.
Wu, J. H.; Zaccara, S.; Khuperkar, D.; Kim, H.; Tanenbaum, M. E.; Jaffrey, S. R. Live imaging of mRNA using RNA-stabilized fluorogenic proteins. Nat. Methods 2019, 16, 862–865.
Ren, K. W.; Liu, Y.; Wu, J.; Zhang, Y.; Zhu, J.; Yang, M.; Ju, H. X. A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery. Nat. Commun. 2016, 7, 13580.
Cui, M. R.; Chen, L. X.; Li, X. L.; Xu, J. J.; Chen, H. Y. NIR remote-controlled "lock–unlock" nanosystem for imaging potassium ions in living cells. Anal. Chem. 2020, 92, 4558–4565.
Tang, Y. F.; Li, Y. Y.; Hu, X. M.; Zhao, H.; Ji, Y.; Chen, L.; Hu, W. B.; Zhang, W. S.; Li, X.; Lu, X. M. et al. "Dual lock-and-key"-controlled nanoprobes for ultrahigh specific fluorescence imaging in the second near-infrared window. Adv. Mater. 2018, 30, 1801140.
Yan, N.; Lin, L.; Xu, C. N.; Tian, H. Y.; Chen, X. S. A GSH-gated DNA nanodevice for tumor-specific signal amplification of microRNA and MR imaging–guided theranostics. Small 2019, 15, 1903016.
Xie, X. L.; Tang, F. Y.; Shangguan, X. Y.; Che, S. Y.; Niu, J. Y.; Xiao, Y. S.; Wang, X.; Tang, B. Two-photon imaging of formaldehyde in live cells and animals utilizing a lysosome-targetable and acidic pH-activatable fluorescent probe. Chem. Commun. 2017, 53, 6520– 6523.
Li, J. C.; Cui, D.; Huang, J. G.; He, S. S.; Yang, Z. B.; Zhang, Y.; Luo, Y.; Pu, K. Y. Organic semiconducting pro-nanostimulants for near-infrared photoactivatable cancer immunotherapy. Angew. Chem., Int. Ed. 2019, 58, 12680–12687.
Wen, M.; Ouyang, J.; Wei, C. W.; Li, H.; Chen, W. S.; Liu, Y. N. Artificial enzyme catalyzed cascade reactions: Antitumor immunotherapy reinforced by NIR-Ⅱ light. Angew. Chem., Int. Ed. 2019, 58, 17425–17432.
Wang, Z. Q.; Wang, L. C.; Prabhakar, N.; Xing, Y. X.; Rosenholm, J. M.; Zhang, J. X.; Cai, K. Y. CaP coated mesoporous polydopamine nanoparticles with responsive membrane permeation ability for combined photothermal and siRNA therapy. Acta Biomater. 2019, 86, 416–428.
Zhou, C. Y.; Zhang, L.; Sun, T.; Zhang, Y.; Liu, Y. D.; Gong, M. F.; Xu, Z. S.; Du, M. M.; Liu, Y.; Liu, G. et al. Activatable NIR-Ⅱ plasmonic nanotheranostics for efficient photoacoustic imaging and photothermal cancer therapy. Adv. Mater. 2021, 33, 2006532.
Wu, Y. T.; Yang, Z. L.; Lu, Y. Photocaged functional nucleic acids for spatiotemporal imaging in biology. Curr. Opin. Chem. Biol. 2020, 57, 95–104.
Tam, D. Y.; Zhuang, X. Y.; Wong, S. W.; Lo, P. K. Photoresponsive self-assembled DNA nanomaterials: Design, working principles, and applications. Small 2019, 15, 1805481.
Seyfried, P.; Eiden, L.; Grebenovsky, N.; Mayer, G.; Heckel, A. Photo-tethers for the (multi-)cyclic, conformational caging of long oligonucleotides. Angew. Chem., Int. Ed. 2017, 56, 359–363.
Zhao, X. X.; Zhang, L. L.; Gao, W. Y.; Yu, X. L.; Gu, W.; Fu, W. L.; Luo, Y. Spatiotemporally controllable microRNA imaging in living cells via a near-infrared light-activated nanoprobe. ACS Appl. Mater. Interfaces 2020, 12, 35958–35966.
Shen, Y.; Li, Z.; Wang, G. L.; Ma, N. Photocaged nanoparticle sensor for sensitive microRNA imaging in living cancer cells with temporal control. ACS Sens. 2018, 3, 494–503.
Li, D. X.; Zhou, W. J.; Yuan, R.; Xiang, Y. A DNA-fueled and catalytic molecule machine lights up trace under-expressed microRNAs in living cells. Anal. Chem. 2017, 89, 9934–9940.
Wang, W. J.; Satyavolu, N. S. R.; Wu, Z. K.; Zhang, J. R.; Zhu, J. J.; Lu, Y. Near-infrared photothermally activated DNAzyme–gold nanoshells for imaging metal ions in living cells. Angew. Chem., Int. Ed. 2017, 56, 6798–6802.
Dai, W. H.; Dong, H. F.; Guo, K. K.; Zhang, X. J. Near-infrared triggered strand displacement amplification for microRNA quantitative detection in single living cells. Chem. Sci. 2018, 9, 1753–1759.
Yan, N.; Wang, X. J.; Lin, L.; Song, T. J.; Sun, P. J.; Tian, H. Y.; Liang, H. J.; Chen, X. S. Gold nanorods electrostatically binding nucleic acid probe for in vivo microRNA amplified detection and photoacoustic imaging-guided photothermal therapy. Adv. Funct. Mater. 2018, 28, 1800490.
Xue, Q. W.; Kong, Y. C.; Wang, H. S.; Jiang, W. Liposome-encoded magnetic beads initiated by padlock exponential rolling circle amplification for portable and accurate quantification of microRNAs. Chem. Commun. 2017, 53, 10772–10775.
Xu, L. G.; Gao, Y. F.; Kuang, H.; Liz-Marzán, L. M.; Xu, C. L. MicroRNA-directed intracellular self-assembly of chiral nanorod dimers. Angew. Chem., Int. Ed. 2018, 57, 10544–10548.
Wei, J.; Wang, H. M.; Gong, X.; Wang, Q.; Wang, H.; Zhou, Y. J.; Wang, F. A. A proteinase-free DNA replication machinery for in vitro and in vivo amplified microRNA imaging. Nucleic Acids Res. 2020, 48, e60.
Li, L.; Jiang, Y.; Cui, C.; Yang, Y.; Zhang, P. H.; Stewart, K.; Pan, X. S.; Li, X. W.; Yang, L.; Qiu, L. P. et al. Modulating aptamer specificity with pH-responsive DNA bonds. J. Am. Chem. Soc. 2018, 140, 13335–13339.
Thompson, I. A. P.; Zheng, L. W.; Eisenstein, M.; Soh, H. T. Rational design of aptamer switches with programmable pH response. Nat. Commun. 2020, 11, 2946.
Wang, H.; Chen, H.; Huang, Z. P.; Li, T. D.; Deng, A. M.; Kong, J. L. DNase i enzyme-aided fluorescence signal amplification based on graphene oxide-DNA aptamer interactions for colorectal cancer exosome detection. Talanta 2018, 184, 219–226.
Wang, J.; Wang, Y. Q.; Hu, X. X.; Zhu, C. L.; Ma, Q. Q.; Liang, L.; Li, Z. H.; Yuan, Q. Dual-aptamer-conjugated molecular modulator for detecting bioactive metal ions and inhibiting metal-mediated protein aggregation. Anal. Chem. 2019, 91, 823–829.
Raducanu, V. S.; Rashid, F.; Zaher, M. S.; Li, Y. Y.; Merzaban, J. S.; Hamdan, S. M. A direct fluorescent signal transducer embedded in a DNA aptamer paves the way for versatile metal-ion detection. Sens Actuators B Chem. 2020, 304, 127376.
Walter, H. K.; Bauer, J.; Steinmeyer, J.; Kuzuya, A.; Niemeyer, C. M.; Wagenknecht, H. A. "DNA origami traffic lights" with a split aptamer sensor for a bicolor fluorescence readout. Nano Lett. 2017, 17, 2467–2472.
Zheng, M. Q.; Kang, Y. F.; Liu, D.; Li, C. Y.; Zheng, B.; Tang, H. W. Detection of ATP from "fluorescence" to "enhanced fluorescence" based on metal-enhanced fluorescence triggered by aptamer nanoswitch. Sens Actuators B Chem. 2020, 319, 128263.
Xiao, M. S.; Chandrasekaran, A. R.; Ji, W.; Li, F.; Man, T. T.; Zhu, C. F.; Shen, X. Z.; Pei, H.; Li, Q.; Li, L. Affinity-modulated molecular beacons on MoS2 nanosheets for microRNA detection. ACS Appl. Mater. Interfaces 2018, 10, 35794–35800.
Chen, Z.; Lu, J. X.; Xiao, F.; Huang, Y. S.; Zhang, X. J.; Tian, L. L. A self-delivery DNA nanoprobe for reliable microRNA imaging in live cells by aggregation induced red-shift-emission. Chem. Commun. 2020, 56, 1501–1504.
Xiao, M. S.; Man, T. T.; Zhu, C. F.; Pei, H.; Shi, J. Y.; Li, L.; Qu, X. M.; Shen, X. Z.; Li, J. MoS2 nanoprobe for microRNA quantification based on duplex-specific nuclease signal amplification. ACS Appl. Mater. Interfaces 2018, 10, 7852–7858.
Qi, L.; Xiao, M. S.; Wang, X. W.; Wang, C.; Wang, L. H.; Song, S. P.; Qu, X. M.; Li, L.; Shi, J. Y.; Pei, H. DNA-encoded Raman-active anisotropic nanoparticles for microRNA detection. Anal. Chem. 2017, 89, 9850–9856.
Xiao, M. S.; Wang, X. W.; Li, L.; Pei, H. Stochastic RNA walkers for intracellular microRNA imaging. Anal. Chem. 2019, 91, 11253– 11258.
Zhao, J.; Chu, H. Q.; Zhao, Y.; Lu, Y.; Li, L. L. A NIR light gated DNA nanodevice for spatiotemporally controlled imaging of microRNA in cells and animals. J. Am. Chem. Soc. 2019, 141, 7056–7062.
Gareau, D.; Desrosiers, A.; Vallée-Bélisle, A. Programmable quantitative DNA nanothermometers. Nano Lett. 2016, 16, 3976– 3981.
Hastman, D. A.; Melinger, J. S.; Aragonés, G. L.; Cunningham, P. D.; Chiriboga, M.; Salvato, Z. J.; Salvato, T. M.; Brown Ⅲ, C. W.; Mathur, D.; Medintz, I. L. et al. Femtosecond laser pulse excitation of DNA-labeled gold nanoparticles: Establishing a quantitative local nanothermometer for biological applications. ACS Nano 2020, 14, 8570–8583.
Wu, Y. S.; Liu, J. J.; Wang, Y.; Li, K.; Li, L.; Xu, J. H.; Wu, D. C. Novel ratiometric fluorescent nanothermometers based on fluorophores- labeled short single-stranded DNA. ACS Appl. Mater. Interfaces 2017, 9, 11073–11081.
Lee, J. H.; Ryu, J. S.; Kang, Y. K.; Lee, H.; Chung, H. J. Polydopamine sensors of bacterial hypoxia via fluorescence coupling. Adv. Funct. Mater. 2021, 31, 2007993.
Wu, D.; Duan, X. H.; Guan, Q. Q.; Liu, J.; Yang, X.; Zhang, F.; Huang, P.; Shen, J.; Shuai, X. T.; Cao, Z. Mesoporous polydopamine carrying manganese carbonyl responds to tumor microenvironment for multimodal imaging-guided cancer therapy. Adv. Funct. Mater. 2019, 29, 1900095.
Tang, J.; Liu, J.; Li, C. L.; Li, Y. Q.; Tade, M. O.; Dai, S.; Yamauchi, Y. Synthesis of nitrogen-doped mesoporous carbon spheres with extra-large pores through assembly of diblock copolymer micelles. Angew. Chem., Int. Ed. 2015, 127, 598–603.
Liu, Y. M.; Xu, J.; He, L.; Cao, Y.; He, H. Y.; Zhao, D. Y.; Zhuang, J. H.; Fan, K. N. Facile synthesis of Fe-loaded mesoporous silica by a combined detemplation–incorporation process through fenton's chemistry. J. Phys. Chem. C 2008, 112, 16575–16583.
Liang, C. P.; Ma, P. Q.; Liu, H.; Guo, X. G.; Yin, B. C.; Ye, B. C. Rational engineering of a dynamic, entropy-driven DNA nanomachine for intracellular microRNA imaging. Angew. Chem., Int. Ed. 2017, 56, 9077–9081.
Lu, H. T.; Yang, F.; Liu, B. H.; Zhang, K.; Cao, Y.; Dai, W. H.; Li, W. J.; Dong, H. F. Intracellular low-abundance microRNA imaging by a NIR-assisted entropy-driven DNA system. Nanoscale Horiz. 2019, 4, 472–479.
Tang, L.; Mo, S.; Liu, S. G.; Li, N.; Ling, Y.; Li, N. B.; Luo, H. Q. Preparation of bright fluorescent polydopamine-glutathione nanoparticles and their application for sensing of hydrogen peroxide and glucose. Sens Actuators B Chem. 2018, 259, 467–474.
Vaish, A.; Vanderah, D. J.; Richter, L. J.; Dimitriou, M.; Steffens, K. L.; Walker, M. L. Dithiol-based modification of poly(dopamine): Enabling protein resistance via short-chain ethylene oxide oligomers. Chem. Commun. 2015, 51, 6591–6594.
Wang, Z. Q.; Zhang, J. X.; Chen, F.; Cai, K. Y. Fluorescent miRNA analysis enhanced by mesopore effects of polydopamine nanoquenchers. Analyst 2017, 142, 2796–2804.
Bu, Y. C.; Xu, T. R.; Zhu, X. J.; Zhang, J.; Wang, L. K.; Yu, Z. P.; Yu, J. H.; Wang, A. D.; Tian, Y. P.; Zhou, H. P. et al. A NIR-I light- responsive superoxide radical generator with cancer cell membrane targeting ability for enhanced imaging-guided photodynamic therapy. Chem. Sci. 2020, 11, 10279–10286.
Li Volsi, A.; de Aberasturi, D. J.; Henriksen-Lacey, M.; Giammona, G.; Licciardi, M.; Liz-Marzán, L. M. Inulin coated plasmonic gold nanoparticles as a tumor-selective tool for cancer therapy. J. Mater. Chem. B 2016, 4, 1150–1155.
Costa, E. C.; Gaspar, V. M.; Marques, J. G.; Coutinho, P.; Correia, I. J. Evaluation of nanoparticle uptake in co-culture cancer models. PLoS One 2013, 8, e70072.
Zhang, P. H.; He, Z. M.; Wang, C.; Chen, J. N.; Zhao, J. J.; Zhu, X. N.; Li, C. Z.; Min, Q. H.; Zhu, J. J. In situ amplification of intracellular microRNA with MNAzyme nanodevices for multiplexed imaging, logic operation, and controlled drug release. ACS Nano 2015, 9, 789–798.
Publication history
Copyright
Acknowledgements
This work was supported in part by the National Natural Science Foundation of China (NSFC, Nos. 51773022, 51825302, 21734002), Project No. 2019CDQYSW041 supported by the Fundamental Research Funds for the Central Universities, Graduate Scientific Research and Innovation Foundation of Chongqing, China (No. CYB20068), and the 100 Talents Program of Chongqing University (J. Z.). We would like to thank the Analytical and Testing Center of Chongqing University for the assistance during particle structure characterizations, and Chongqing Hospital of Traditional Chinese Medicine for providing animal feeding.
FEEDBACK 
TOP