Dual Switchable CRET-Induced Luminescence of ... - ACS Publications

Sep 12, 2014 - The hemin/G-quadruplex-catalyzed generation of chemiluminescence through the oxidation of luminol by H2O2 stimulates the chemiluminesce...
6 downloads 10 Views 3MB Size
Download PDF
Letter pubs.acs.org/NanoLett

Dual Switchable CRET-Induced Luminescence of CdSe/ZnS Quantum Dots (QDs) by the Hemin/G-Quadruplex-Bridged Aggregation and Deaggregation of Two-Sized QDs Lianzhe Hu,† Xiaoqing Liu,† Alessandro Cecconello, and Itamar Willner* Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel S Supporting Information *

ABSTRACT: The hemin/G-quadruplex-catalyzed generation of chemiluminescence through the oxidation of luminol by H2O2 stimulates the chemiluminescence resonance energy transfer (CRET) to CdSe/ZnS quantum dots (QDs), resulting in the luminescence of the QDs. By the cyclic K+-ion-induced formation of the hemin/G-quadruplex linked to the QDs, and the separation of the G-quadruplex in the presence of 18crown-6-ether, the ON-OFF switchable CRET-induced luminescence of the QDs is demonstrated. QDs were modified with nucleic acids consisting of the G-quadruplex subunits sequences and of programmed domains that can be crosslinked through hybridization, using an auxiliary scaffold. In the presence of K+-ions, the QDs aggregate through the cooperative stabilization of K+-ion-stabilized G-quadruplex bridges and duplex domains between the auxiliary scaffold and the nucleic acids associated with the QDs. In the presence of 18-crown-6-ether, the K+-ions are eliminated from the G-quadruplex units, leading to the separation of the aggregated QDs. By the cyclic treatment of the QDs with K+-ions/18-crown-6-ether, the reversible aggregation/deaggregation of the QDs is demonstrated. The incorporation of hemin into the K+-ion-stabilized G-quadruplex leads to the ON-OFF switchable CRET-stimulated luminescence of the QDs. By the mixing of appropriately modified two-sized QDs, emitting at 540 and 610 nm, the dual ON-OFF activation of the luminescence of the QDs is demonstrated. KEYWORDS: Chemiluminescence, DNA, DNAzyme, switch, crown ether, fluorescence

S

hemin/G-quadruplex, the horseradish peroxidase-mimicking DNAzyme, with QDs and the use of the chemiluminescence resonance energy transfer (CRET) process as an optical readout signal for DNA19 or aptamer-substrate sensing events.20 In these systems, the hemin/G-quadruplex catalyzed the oxidation of luminol by H2O2, and this generated the chemiluminescence that stimulated the CRET process to the QDs. By appropriate functionalization of different-sized QDs with hemin/G-quadruplex structures, the multiplexed analysis of genes or aptamer-substrate complexes by the CRET signals was demonstrated. The information encoded in the base-sequences of nucleic acids has been widely applied to develop DNA switches and machines.21 Different external triggers, such as the pH-induced formation or dissociation of i-motif structures,22 the metal-ion/ ligand-stimulated formation of nucleic acid duplexes and their dissociation,19a,23 and the K+-ion/receptor (crown ether)dependent formation and dissociation of G-quadruplexes have been applied for the ON/OFF switching of molecular DNA systems or DNA machines.24 The signal-triggered DNA

emiconductor quantum dots, QDs, attract substantial research interest due to their unique photophysical properties reflected by high-luminescence quantum yields, size-controlled luminescence, stability against photobleaching, and narrow emission bands exhibiting a large Stokes shift.1,2 Different applications of semiconductor QDs were reported, including their use to assemble solar cells for energy conversion,3 using the QDs as photocatalysts,4 sensors,5 nanomaterials for intracellular imaging,6 and as a functional material to assemble optoelectronic devices.7 The integration of biomaterials with semiconductor QDs yields functional hybrids for optical or photoelectrochemical sensing.8 For example, nucleic acid-modified QDs were applied for the detection of DNA,9 aptamer-substrate complexes10 and metal ions11 such as Hg2+ or Ag+ ions. The fluorescence of the QDs,12 the Förster resonance energy transfer (FRET),13 or the electron transfer quenching14 of the QDs by electron acceptor units, were implemented as optical readout signals for biosensing processes. Also, the assembly of nucleic acid-functionalized semiconductor QDs on electrodes was used for the photoelectrochemical detection of DNA15 or aptamer-substrate complexes.16 By applying different sized QDs, the multiplexed analysis of DNAs17 or aptamer-substrate complexes18 were demonstrated. An interesting paradigm for the application of QDs for optical biosensing has involved the integration of the © 2014 American Chemical Society

Received: August 27, 2014 Revised: September 11, 2014 Published: September 12, 2014 6030

dx.doi.org/10.1021/nl503299f | Nano Lett. 2014, 14, 6030−6035

Nano Letters

Letter

Figure 2. (A) K+-ion/18-crown-6-ether switchable assembly and disassembly of the K+-stabilized hemin/G-quadruplex. The formation of the hemin/G-quadruplex yields the horseradish peroxidase mimicking DNAzyme that catalyzes the oxidation of ABTS2− to ABTS•− by H2O2, or catalyzes the generation of chemiluminescence upon the oxidation of luminol by H2O2. (B) Chemiluminescence (CL) spectra corresponding to: (a) The separated nucleic acid components in the absence of added K+-ions. (b) The addition of K+-ions and the formation of the hemin/G-quadruplex. (c) The addition of 18-crown6-ether, and dissociation of the G-quadruplex. (d) The readdition of K+-ions. Inset: cyclic switchable ON-OFF generation of chemiluminescence upon the K+-ion/18-crown-6-ether-stimulated formation and dissociation of the hemin/G-quadruplex supramolecular structure.

Figure 1. (A) K+-ion/18-crown-6-ether-induced cyclic formation and dissociation of a hemin/G-quadruplex associated with CdSe/ZnS QDs, and the switchable ON and OFF activation of the luminescence of QDs through the CRET process. (B) Chemiluminescence and luminescence spectra corresponding to (a) the K+-ion-stabilized hemin/G-quadruplex associated with the QDs. (b) the addition of 18-crown-6-ether to the system and the dissociation of the hemin/Gquadruplex. Inset: Cyclic switchable CRET-stimulated luminescence of the CdSe/ZnS ODs at λ = 610 nm (I) in the presence of added K+-ion (switch-ON), and (II) upon the addition of 18-crown-6-ether (switchOFF). The band at λ = 430 nm corresponds to the resulting chemiluminescence, while the band at λ = 610 nm corresponds to the luminescence generated by the CRET-stimulated excitation of the QDs.

subsequently modified with the respective amine-functionalized nucleic acids. In the first step, the 610 nm emitting CdSe/ZnS QDs were modified with the nucleic acid (1) that included the G-rich sequence capable to form the G-quadruplex nanostructure. The loading of (1) associated with the 610 nm emitting QDs was determined spectroscopically to be 12 per particle. Figure 1 depicts the switchable hemin/G-quadruplex stimulated CRET process between the horseradish peroxidase mimicking DNAzyme and the QDs. In the presence of K+-ions and hemin, the nucleic acid (1) associated with the QDs self-assembles into the hemin/G-quadruplex catalytic nanostucture, Figure 1A. In the presence of H2O2/luminol, the catalyzed generation of chemiluminescence activates the CRET process to the QDs, resulting in the triggering of the luminescence of the QDs, λ= 610 nm, Figure 1B, curve a, switch-ON. Note that in the absence of K+-ions, yet in the presence of hemin and H2O2/ luminol, much lower chemiluminescence and CRET processes are observed, implying that the K+-ions are essential to yield the hemin/G-quadruplex complex. Subjecting the system to 18crown-6-ether eliminates the K+-ions from the G-quadruplex, resulting in its separation and the dissociation of the hemin. This switches off the catalytic activity of the system to yield chemiluminescence and blocks the subsequent CRET process, switch-OFF, Figure 1B, curve b. By the cyclic additions of K+ions and 18-crown-6-ether, the system is reversibly switched between ON and OFF states, respectively, Figure 1B, inset. Note that the secondary CRET signal of the QDs is slightly lower as compared to the primary CRET signal. This is due to a side-effect of the 18-crown-6-ether that quenches slightly the

switches were used to stimulate solution-to-hydrogel transitions,25 to control the opening/closures of nanopores,26 and to switch biocatalytic transformations.27 In the present study, we report on the cyclic switchable K+ion-stimulated aggregation of CdSe/ZnS QDs, using hemin/Gquadruplex as functional bridging units, and the separation of the aggregated QDs by means of 18-crown-6-ether. In the presence of luminol/H2O2, the hemin/G-quadruplex bridging units catalyze the CRET to the QDs, resulting in the luminescence of the QDs. This leads to the cyclic switching of the luminescence of the QDs between ON and OFF states upon aggregation and deaggregation of the QDs. By using two different-sized QDs, the K+-ion-induced aggregation of the twosized QDs proceeds, using the hemin/G-quadruplex as bridging units. This results in the CRET-stimulated luminescence of the two-sized QDs. By the cyclic K+-ion/crown ether-stimulated aggregation and deaggregation of the QDs, respectively, the dual luminescence of the QDs is switched reversibly between ON and OFF states. Besides demonstrating the assembly of a QDs-based optoelectronic switch that reveals dual luminescence functions, we also highlight the switchable catalytic properties of the hemin/G-quadruplex upon the aggregation and deaggregation of the semiconductor QDs. Different-sized QDs emitting at 610 and 540 nm were modified with glutathione capping layers, and the QDs were 6031

dx.doi.org/10.1021/nl503299f | Nano Lett. 2014, 14, 6030−6035

Nano Letters

Letter

Figure 3. (A) K+-ion/18-crown-6-ether-induced aggregation and deaggregation of the 610 nm CdSe/ZnS emitting QDs using the hemin/Gquadruplex as cross-linker, and the switchable ON and OFF triggering of the luminescence of the QDs through the CRET process. (B) Chemiluminescence and luminescence spectra of the QDs system upon (a) The K+-ion-induced aggregation of the QDs through their cross-linking by the hemin/G-quadruplex DNAzyme unit. (b) The separation of the QDs aggregate upon the addition of 18-crown-6-ether. (c) The readdition of K+-ions to the system. Inset: Cyclic switchable activation and blockage of the luminescence of the QDs: (I) In the presence of the K+-ion-stabilized hemin/G-quadruplex-cross-linked QDs aggregates, switch-ON. (II) In the presence of 18-crown-6-ether that leads to the deaggregation of the crosslinking bridges, and to the deaggeration of the QDs, switch-OFF. (C) STEM images corresponding to (I) the separated (5a)- and (6a)-modified QDs in the presence of the scaffold (2) and in the absence of K+-ions, (II) the aggregate of the QDs upon addition of K+-ions to the system, and the formation of the K+-ion-stabilized G-quadruplex-cross-linked QDs, and (III) upon the further addition of 18-crown-6-ether to the system, leading to the deaggregation of the QDs.

hemin is catalytically inactive, switch-OFF (Figure 2B, curve a). In the presence of K+-ions and hemin, the overhangs II and IV, associated with (3) and (4), self-assemble into the hemin/Gquadruplex and this synergetically stabilizes the formation of the supramolecular three-component duplex nanostructure (2)/(3)/(4). The resulting nanostructure reveals horseradish peroxidase catalytic functions, and it catalyzes the oxidation of luminol by H2O2 and the generation of chemiluminescence, switch-ON. Figure 2B, curve b shows the chemiluminescence response of the system. Treatment of the switched-on DNAzyme structure with 18-crown-6-ether eliminates the K+ions from the G-quadruplex, resulting in its separation, and the dissociation of the hemin unit. This leads to the catalytically inactive templated structure (2)/(3)/(4), that does not lead to the generation of chemiluminescence, Figure 2B, curve c. Readdtion of K+ ions regenerates the chemiluminescence spectrum of the system, Figure 2B, curve d. By subjecting the system to K+-ions and 18-crown-6-ether, the generation of chemiluminescence by the system is cycled between ON and OFF states, Figure 2B, inset. For the ON/OFF cycled oxidation of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS2−, by H 2O2 using the hybrid (2)/(3)/(4), see

chemiluminescence generated by the luminol/H2O2/hemin Gquadruplex system thus leading to a lower CRET signal. The successful ON/OFF switching of the CRET process between the hemin/G-quadruplex and the QDs by means of K+-ion/18-crown-6-ether was then implemented to design the switchable CRET process in hemin/G-quadruplex aggregated/ deaggregated QDs structures. In the first step, we designed the switchable catalytic scaffold that is aimed to bridge the QDs, Figure 2A. The nucleic acid (2) acts as a template for the hybridization with the nucleic acids (3) and (4). The nucleic acid (3) consists of the sequence I, that is complementary to domain I′ of the template (2), and the single stranded overhang II that is composed of three quarters of the G-quadruplex. The nucleic acid (4) includes sequence III, complementary to the domain III′ of the template (2), and it is extended by the single stranded overhang IV, composed of a quarter of the Gquadruplex structure, resulting in a tricomponent system that is catalytically inactive, switch-OFF. The number of complementary bases between domains I and III, and the scaffold (2) is insufficient to form stable duplexes at room temperature, resulting in the strands (2), (3), and (4) in a separated form. The resulting composite of the nucleic acids in the presence of 6032

dx.doi.org/10.1021/nl503299f | Nano Lett. 2014, 14, 6030−6035

Nano Letters

Letter

luminescence QDs (DNA loading: 12 and 10, respectively). Similarly, the 540 nm emitting QDs were modified with the amino-modified nucleic acids (5) and (6) to yield the (5b)- and (6b)-modified 540 nm QDs (DNA loading: 6 and 5, respectively). The cyclic assembly and dissociation of the supramolecular three-component structure consisting of (2)/ (4)/(5a)-modified QDs and (2)/(3)/(6b)-modified QDs were characterized (see Supporting Information, Figures S3 and S4). The (5a)- and (6a)-modified QDs were then mixed with the nucleic acid scaffold (2) in the presence of hemin. The resulting components exist in their separated forms. Subjecting the system to K+-ions results in the aggregation of the 610 nm emitting QDs through the formation of the hemin/Gquadruplex bridges, Figure 3A. In the presence of luminol/ H2O2, the hemin/G-quadruplex units bridging the QDs catalyze the generation of chemiluminescence and the accompanying CRET process to the QDs, thus triggering-on the luminescence of the QDs, switch-ON. Figure 3B, curve a, depicts the characteristic chemiluminescence of the luminol/ H2O2 system at λ = 430 nm and the accompanying CRETinduced luminescence of the QDs at λ = 610 nm. From the luminescence intensity of the QDs, we estimate the CRET efficiency to be ca. 24.5%. Subjecting the hemin/G-quadruplexbridged aggregated QDs to 18-crown-6-ether results in the separation of the bridging units and to the deaggregation of the QDs to the individual components. This yields a catalytically inactive mixture that has a low chemiluminescence; thus, the CRET process is prohibited, and only a residual luminescence of the QDs is observed, switch-OFF, Figure 3B, curve b. By the cyclic treatment of the system with K+-ions and 18-crown-6ether, the luminescence of the QDs is reversibly switched ON and OFF through the CRET process, Figure 3B, inset. The cyclic formation of the G-quadruplex-bridged aggregated QDs in the presence of K+-ions, and the separation of the aggregates upon the addition of the 18-crown-6-ether, were further supported by STEM experiments, Figure 3C. In the absence of K+-ions, the (5a)- and (6a)-modified QDs and (2) exist in the separated forms, panel I. In the presence of K+-ions, the (5a)- and (6a)-modified QDs, and the scaffold (2), aggregation proceeds, panel II. In turn, treatment of the resulting aggregates with the crown-ether yields mostly individual single QDs, panel III. The transitions between the aggregated QDs structures and the separated individual QDs upon the sequential additions of K+-ions and 18-crown-6-ether are reversible. The formation of the K+-ion-stimulated hemin/G-quadruplex DNAzyme bridged QDs aggregates, was also supported by following the DNAzyme-catalyzed oxidation of ABTS2−, by H2O2 to the colored product, ABTS•− (see Supporting Information, Figure S5). Finally, the two-sized QDs (luminescent at 610 and 540 nm) were reversibly aggregated by the hemin/G-quadruplex bridges, and the triggered dual luminescence of the QDs was activated by the hemin/G-quadruplex-catalyzed CRET process. In these experiments, the scaffold (2) was mixed with (5a)-functionalized 610 nm-luminescent QDs and with (6b)-modified 540 nm-luminescent QDs, in the presence of hemin. In the absence of K+-ions, the system consists of the separated constituents, Figure 4A. In this state the system lacks catalytic activity toward the generation of chemiluminescence, and the secondary activation of the luminescence of the QDs via the CRET mechanism is prevented. Addition of K+-ions induces the hemin/G-quadruplex bridged aggregation of the two-sized QDs. In the presence of luminol/H2O2 the resulting aggregate

Figure 4. (A) K+-ion/18-crown-6-ether-induced aggregation and deaggregation of two-sized nucleic acid-functionalized QDs emitting at λ = 540 nm and λ = 610 nm using the hemin/G-quadruplex as cross-linker, and the dual, switchable, CRET-induced luminescence of the two-sized QDs. (B) Chemiluminescence and luminescence spectra corresponding to (a) the aggregated hemin/G-quadruplex-cross-linked QDs aggregate generated upon the addition of K+-ions to the (5a)and (6a)-functionalized QDs in the presence of (2), switch-ON and (b) the addition of 18-crown-6 ether and the separation of the aggregated QDs. (c) the readdition of K+-ions to the system. Inset: Cyclic ON and OFF activation of the luminescence of (■) the 540 nm QDs and (●) the 610 nm emitting QDs, where (I) corresponds to the luminescence intensities generated by the aggregated QDs in the presence of K+-ions and (II) corresponds to the deaggregated QDs in the presence of 18-crown-6-ether. The band at λ = 430 nm corresponds to the chemiluminescence spectrum, while the bands at λ = 540 nm and λ = 610 nm correspond to the luminescence spectra of the respective QDs.

Supporting Information, Figure S1. Also, for further FRET experiments, supporting the formation of the G-quadruplexstabilized three-component system, see Supporting Information, Figure S2. In the next step, the 610 nm emitting QDs were functionalized with the amino-modified nucleic acid sequences, (5) and (6), to yield the (5a)- and (6a)-modified 610 nm 6033

dx.doi.org/10.1021/nl503299f | Nano Lett. 2014, 14, 6030−6035

Nano Letters

Letter

Steigerwald, M. L.; Brus, L. E. Annu. Rev. Phys. Chem. 1990, 41, 477− 496. (2) (a) Eychmüller, A. J. Phys. Chem. B 2000, 104, 6514−6528. (b) Tang, Z.; Kotov, N. A.; Giersig, M. Science 2002, 297, 237−240. (c) Hines, D. A.; Kamat, P. V. ACS Appl. Mater. Interfaces 2014, 6, 3041−3057. (3) (a) Kamat, P. V. J. Phys. Chem. C 2008, 112, 18737−18753. (b) Schaller, R. D.; Klimov, V. I. Phys. Rev. Lett. 2004, 92, 186601. (c) Alivisatos, A. P. J. Phys. Chem. 1996, 100, 13226−13239. (4) (a) Thompson, T. L.; Yates, J. T. Top. Catal. 2005, 35, 197−210. (b) Harris, C.; Kamat, P. V. ACS Nano 2009, 3, 682−690. (c) Efrati, A.; Yehezkeli, O.; Tel-Vered, R.; Michaeli, D.; Nechushtai, R.; Willner, I. ACS Nano 2012, 6, 9258−9266. (5) (a) Jaiswal, J. K.; Mattoussi, H.; Mauro, J. M.; Simon, S. M. Nat. Biotechnol. 2003, 21, 47−51. (b) Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H. Nat. Mater. 2005, 4, 435−446. (c) Freeman, R.; Willner, I. Chem. Soc. Rev. 2012, 41, 4067−4085. (d) Freeman, R.; Girsh, J.; Willner, I. ACS Appl. Mater. Interfaces 2013, 5, 2815−2834. (6) (a) Derfus, A. M.; Chan, W. C. W.; Bhatia, S. N. Nano Lett. 2004, 4, 11−18. (b) Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan, G.; Wu, A. M.; Gambhir, S. S.; Weiss, S. Science 2005, 307, 538−544. (c) Alivisatos, A. P.; Gu, W.; Larabell, C. Annu. Rev. Biomed. Eng. 2005, 7, 55−76. (7) Kim, J. Y.; Voznyy, O.; Zhitomirsky, D.; Sargent, E. H. Adv. Mater. 2013, 25, 4986−5010. (8) (a) Gill, R.; Zayats, M.; Willner, I. Angew. Chem., Int. Ed. 2008, 47, 7602−7625. (b) Zrazhevskiy, P.; Sena, M.; Gao, X. Chem. Soc. Rev. 2010, 39, 4326−4354. (c) Algar, W. R.; Kim, H.; Medintz, I. L.; Hildebrandt, N. Coord. Chem. Rev. 2014, 263−264, 65−85. (9) Dyadyusha, L.; Yin, H.; Jaiswal, S.; Brown, T.; Baumberg, J. J.; Booy, F. P.; Melvin, T. Chem. Commun. 2005, 25, 3201−3203. (10) (a) Bagalkot, V.; Zhang, L.; Levy-Nissenbaum, E.; Jon, S.; Kantoff, P. W.; Langer, R.; Farokhzad, O. C. Nano Lett. 2007, 7, 3065−3070. (b) Liu, J.; Lee, J. H.; Lu, Y. Anal. Chem. 2007, 79, 4120− 4125. (11) (a) Chen, Y. F.; Rosenzweig, Z. Anal. Chem. 2002, 74, 5132− 5138. (b) Freeman, R.; Finder, T.; Willner, I. Angew. Chem., Int. Ed. 2009, 48, 7818−7821. (c) Wu, C.-S.; Oo, M. K. K.; Fan, X. ACS Nano 2010, 4, 5897−5904. (12) Gerion, D.; Chen, F. Q.; Kannan, B.; Fu, A. H.; Parak, W. J.; Chen, D. J.; Majumdar, A.; Alivisatos, A. P. Anal. Chem. 2003, 75, 4766−4772. (13) Medintz, I. L.; Clapp, A. R.; Brunel, F. M.; Tiefenbrunn, T.; Uyeda, H. T.; Chang, E. L.; Deschamps, J. R.; Dawson, P. E.; Mattoussi, H. Nat. Mater. 2006, 5, 581−589. (14) (a) Yuan, J.; Guo, W.; Yang, X.; Wang, E. Anal. Chem. 2009, 81, 362−368. (b) Sharon, E.; Freeman, R.; Willner, I. Anal. Chem. 2010, 82, 7073−7077. (15) (a) Willner, I.; Patolsky, F.; Wasserman, J. Angew. Chem., Int. Ed. 2001, 40, 1861−1864. (b) Zhao, W. W.; Xu, J. J.; Chen, H. Y. Chem. Rev. 2014, 114, 7421−7441. (16) Golub, E.; Pelossof, G.; Freeman, R.; Zhang, H.; Willner, I. Anal. Chem. 2009, 81, 9291−9298. (17) (a) Han, M.; Gao, X.; Su, J. Z.; Nie, S. Nat. Biotechnol. 2001, 19, 631−635. (b) Wang, J.; Liu, G.; Merkoçi, A. J. Am. Chem. Soc. 2003, 125, 3214−3215. (c) Algar, W. R.; Krull, U. J. Anal. Bioanal. Chem. 2010, 398, 2439−2449. (d) Freeman, R.; Liu, X.; Willner, I. Nano Lett. 2011, 11, 4456−4461. (e) Giri, S.; Sykes, E. A.; Jennings, T. L.; Chan, W. C. W. ACS Nano 2011, 5, 1580−1587. (18) (a) Hansen, J. A.; Wang, J.; Kawde, A. N.; Xiang, Y.; Gothelf, K. V.; Collins, G. J. Am. Chem. Soc. 2006, 128, 2228−2229. (b) Kang, W. J.; Chae, J. R.; Cho, Y. L.; Lee, J. D.; Kim, S. Small 2009, 5, 2519− 2522. (19) (a) Liu, X.; Niazov-Elkan, A.; Wang, F.; Willner, I. Nano Lett. 2013, 13, 219−225. (b) Freeman, R.; Liu, X.; Willner, I. J. Am. Chem. Soc. 2011, 133, 11597−11604. (20) (a) Liu, X.; Freeman, R.; Golub, E.; Willner, I. ACS Nano 2011, 5, 7648−7655. (b) Freeman, R.; Girsh, J.; Jou, A. F.; Ho, J. A.; Hug,

triggers the CRET process, and this triggers on the luminescence of the two-sized QDs, at 610 and 540 nm. Figure 4B, curve a, depicts the luminescence spectrum of the system in the presence of the hemin/G-quadruplex-bridged aggregates composed of the two-sized QDs. Treatment of the system with 18-crown-6-ether separates the hemin/G-quadruplex bridges and yields individual QDs. This leads to a catalytically inactive system, resulting in the blocking of the CRET process, Figure 4B, curve b. By the cyclic treatment of the system with K+-ions and 18-crown-6-ether, the CRET stimulated luminescence of the two QDs is reversibly switched between ON and OFF states. For the STEM images of the K+ion-stimulated aggregation of the QDs and their separation following the addition of 18-crown-6-ether, see Supporting Information, Figure S6. In conclusion, the present study has demonstrated the switchable aggregation and deaggregation of CdSe/ZnS QDs using the K+-ion-stimulated formation of G-quadruplexes as bridging units of the aggregates, and the 18-crown-6-etherinduced separation of the G-quadruplexes, accompanied by the deaggregation of the CdSe/ZnS QDs. By the incorporation of hemin into the K+-ion-stabilized G-quadruplex bridging units, the oxidation of luminol by H2O2, catalyzed by the hemin/Gquadruplex DNAzyme, and the generation of chemiluminescence were demonstrated. The subsequent CRET process to the QDs resulted in the luminescence of the QDs without external irradiation. By the successive interaction of the systems with K+-ions/crown ether, the cyclic formation of the QDs aggregates and their separation were demonstrated, leading to the switchable CRET-induced luminescence of the QDs. These results introduce a new concept for designing switchable photonic devices using DNA/QDs hybrid nanostructures.

■

ASSOCIATED CONTENT

S Supporting Information *

Experimental procedures, the switchable catalytic functions of the (2)/(3)/(4) supramolecular structure, the FRET experiments confirming the K+-ion-stimulated formation of the bridged G-quadruplex supramolecular structure, the CRET process proceeding in the hemin/G-quadruplex QDs assemblies, the switchable catalytic functions of the hemin/Gquadruplex upon the aggregation and deaggregation of the QDs, and the STEM images corresponding to the two-sized QDs upon aggregation and deaggregation. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Tel: +972-2-6585272. Fax: +972-2-6527715. Author Contributions †

L.H. and X.L. contributed equally.

Notes

The authors declare no competing financial interest.

■ ■

ACKNOWLEDGMENTS This study is supported by NanoSensoMach ERC Advanced Grant (267574). REFERENCES

(1) (a) Alivisatos, A. P. J. Phys. Chem. 1996, 100, 13226−13239. (b) Weller, H. Adv. Mater. 1993, 5, 88−95. (c) Bawendi, M. G.; 6034

dx.doi.org/10.1021/nl503299f | Nano Lett. 2014, 14, 6030−6035

Nano Letters

Letter

T.; Dernedde, J.; Willner, I. Anal. Chem. 2012, 84, 6192−6198. (c) Chen, H.; Lin, L.; Li, H.; Lin, J. M. Coord. Chem. Rev. 2014, 263− 264, 86−100. (21) (a) Seeman, N. C. Trends Biochem. Sci. 2005, 30, 119−125. (b) Krishnan, Y.; Simmel, F. C. Angew. Chem., Int. Ed. 2011, 50, 3124− 3156. (c) Goodman, R. P.; Heilemann, M.; Doose, S.; Erben, C. M.; Kapanidis, A. N.; Turberfield, A. J. Nat. Nanotechnol. 2008, 3, 93−96. (d) Liu, X.; Lu, C. H.; Willner, I. Acc. Chem. Res. 2014, 47, 1673− 1680. (e) Li, D.; Song, S. P.; Fan, C. H. Acc. Chem. Res. 2010, 43, 631− 641. (22) (a) Liu, D.; Balasubramanian, S. Angew. Chem., Int. Ed. 2003, 42, 5734−5736. (b) Elbaz, J.; Wang, Z. G.; Orbach, R.; Willner, I. Nano Lett. 2009, 9, 4510−4514. (c) Yang, Y.; Liu, G.; Liu, H.; Li, D.; Fan, C.; Liu, D. Nano Lett. 2010, 10, 1393−1397. (d) Dong, Y. C.; Yang, Z. Q.; Liu, D. S. Acc. Chem. Res. 2014, 47, 1853−1860. (23) (a) Modi, S. M. G. S.; Goswami, D.; Gupta, G. D.; Mayor, S.; Krishnan, Y. Nat. Nanotechnol. 2009, 4, 325−330. (b) Wang, Z. G.; Elbaz, J.; Remacle, F.; Levine, R. D.; Willner, I. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 21996−22001. (24) (a) Ge, B.; Huang, Y. C.; Sen, D.; Yu, H. Z. Angew. Chem., Int. Ed. 2010, 49, 9965−9967. (b) Aleman-Garcia, M. A.; Orbach, R.; Willner, I. Chem.Eur. J. 2014, 20, 5619−5624. (25) Lu, C. H.; Qi, X. J.; Orbach, R.; Yang, H. H.; Mironi-Harpaz, I.; Seliktar, D.; Willner, I. Nano Lett. 2013, 13, 1298−1302. (26) (a) Hou, X.; Guo, W.; Xia, F.; Nie, F. Q.; Dong, H.; Tian, Y.; Wen, L.; Wang, L.; Cao, L.; Yang, Y. J. Am. Chem. Soc. 2009, 131, 7800−7805. (b) Liu, N.; Jiang, Y.; Zhou, Y.; Xia, F.; Guo, W.; Jiang, L. Angew. Chem., Int. Ed. 2013, 52, 2007−2011. (27) Hu, Y.; Wang, F.; Lu, C. H.; Girsh, J.; Golub, E.; Willner, I. Chem.Eur. J. 2014, DOI: 10.1002/chem.201404122.

6035

dx.doi.org/10.1021/nl503299f | Nano Lett. 2014, 14, 6030−6035