Stimuli-responsive DNA Microcapsules for SERS Sensing of Trace

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Biological and Medical Applications of Materials and Interfaces

Stimuli-responsive DNA Microcapsules for SERS Sensing of Trace MicroRNA Xia Yang, Shufan Wang, Yue Wang, Yi He, Yaqin Chai, and Ruo Yuan ACS Appl. Mater. Interfaces, Just Accepted Manuscript • Publication Date (Web): 29 Mar 2018 Downloaded from http://pubs.acs.org on March 29, 2018

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ACS Applied Materials & Interfaces

Stimuli-responsive DNA Microcapsules for SERS Sensing of Trace MicroRNA Xia Yang*1, Shufan Wang1, Yue Wang1,2, Yi He1, Yaqin Chai1, Ruo Yuan∗1 1 Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education; College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China 2 NO.1 High School of DaLian Development Area, Liaoning, China

Abstract In this work, one stimuli-responsive DNA microcapsule was designed to combine duplex-specific nuclease (DSN) amplification strategy and SERS technology for sensitive detection of MicroRNA 155 (miRNA155). Firstly, Toluidine blue (TB) as Raman dye and CaCO3 as core-templates co-precipitated to form TB@CaCO3 composite. Then, DNA networks were layer by layer (LbL) constructed with oligonucleotide layers crosslinked by Linker ssDNA L to lock TB@CaCO3 inside. In the presence of EDTA, the core CaCO3 would be dissolved to form TB loading DNA microcapsule. With target miRNA 155 induced DSN signal amplification, large amount of simulative target ssDNA D were obtained, which can completely complement with the Linker L on the DNA networks, destroying the microcapsule to release TB and obtain a strong Raman signal. So by this smart design, a SERS platform was fabricated based on the stimuli-responsive DNA microcapsule to detect miRNA 155 from 1 fM to 10 nM with a detection limit of 0.67 fM. In the present study, this DNA microcapsule can be programmable and response quickly,

*Corresponding author. E-mail address: [email protected] (X. Yang); [email protected] (R. Yuan)

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which fabricated a new potential biosensing technology for miRNA detection and is anticipated to be applied for clinic diagnosis.

Keywords DNA microcapsules, Duplex-Specific Nuclease (DSN), SERS, MicroRNA

Introduction Currently, microRNAs (miRNAs) analysis has drawn lots of attention because they are regarded as the important biomarker for diagnosis of cancer or neurological disorders1,2.

Many methods

such

as electrochemiluminescence3,

fluorescence4,

electrochemistry5, Surface Enhanced Resonance Raman spectroscopy (SERS) 6 have been proposed to replace traditional Northern blotting7, polymerase chain reaction (PCR) 8 and isothermal oligonucleotide amplification9 approach for sensitive detection of miRNA. Among them, SERS technology is one kind of potential efficient tool for biosensing because it has advantage of easy operation, nondestructive detection and “Finger print” system with Raman dye10,11. Now various polymer and DNA microcapsules are reported for reactor, controlled release of medicine, drug delivery etc

12-15

. The microcapsules are often triggered by

different pH value16, metal ions17, light18, thermal19 to release loading materials. Recently, DNA microcapsules attracted much attention due to its programmable property. For example, it can be designed to recognize the specific enzyme20 and Adenosine Triphosphate (ATP) or vascular epithelial growth factor (VEGF) in cancer cells21, 22. For the target triggered microcapsule, the key factor is that VEGF or ATP must be overexpressed so that they can destroy the capsule. If the amount of target is low, the capsule may not be opened and the amount of releasing cargoes is little. So a target


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induced amplification method can be introduced to realize the sensitive detection of target. Recently, our group has proposed one DNA hydrogel encapsulating Raman dyes based on the target induced amplification method for constructing a sensitive SERS biosensor for miRNA 155 assay23. However, the construction of DNA hydrogel is cumbersome for adding some cross-linking agent and the destroy speed of DNA hydrogel is not very fast. So we designed one DNA capsule with easy assembling process and rapid response speed for sensitive detection of miRNA 155. In this work, an ultra-sensitive SERS platform based on easy assembling stimuli-responsive DNA microcapsule and duplex-specific nuclease (DSN) amplification strategy was fabricated for trace sensing of miRNA 155 ( as shown in Scheme 1). Firstly, the Raman dye toluidine blue (TB) and inorganic CaCO3 microparticles as core-templates co-precipitated and formed TB@CaCO3 composite. Here, CaCO3 was often chosen as a core template to self-assemble the DNA or polymer microcapsules because it can be easily dissolved by EDTA24,25. Due to the advantage, this could avoid a strong acidic or alkaline environment which would affect the DNA microcapsules. Moreover, TB as a common Raman probe can provide an obvious Raman peak. Then, a positively charged layer of Poly(allylaminehydrochloride) (PAH) was coated on the TB@CaCO3 and thus the TB@CaCO3 composite can have an electrostatic attraction to the negative DNA (ssDNA A and B). After that, DNA network was constructed by layer by layer (LbL) method with oligonucleotide layers crosslinked by linker ssDNA L. At this time, TB was locked in the core and no Raman signal was obtained. In the presence of EDTA, the core CaCO3 would be dissolved to form TB loading DNA microcapsule. Nextly, a target miRNA 155 induced DSN amplification was introduced to release simulative target



ssDNA D. Due to the complete complementary of ssDNA D and linker ssDNA L on the DNA capsule, the DNA microcapsule would be destroyed to release TB, realizing a Raman signal, which is positive related to the concentration of miRNA 155. By this way, the amount of TB was related to the concentration of miRNA, indicating that the larger concentration of miRNA, the higher Raman intensity of TB can be obtained. With the DSN amplification, this SERS platform based on the DNA microcapsule could have a wide detection linear range for miRNA 155 between1 fM and 10 nM (detection limit, 0.67 fM). This work could achieve the easy assembling of DNA capsule and rapid response to trace miRNA, which proposed a new strategy for miRNA detection and may have potential to be applied in early diagnosis of cancer.

Scheme 1 (A) Preparation of TB loading DNA microcapsule; (B) Fabrication process of the SERS biosensor, (C) Target miRNA 155 induced DSN amplification process. (D) SERS of the biosensor with target (red curve) and without target (blue curve).

Experimental 4 ACS Paragon Plus Environment

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Preparation of TB@CaCO3 composite The TB@CaCO3 composite was prepared according to the recently reported literature26. Firstly, 0.0945g of Ca(NO3)2·4H2O was dissolved into 20 mL water, then 0.02g of PSS, 0.0006g of TB were injected into the above solution to form solution A. Next, 0.0084g of Na2CO3 was dissolved into 4 mL of ultrapure water with constantly stirring and 0.0040g of PSS was dropped into the solution to form solution B. Afterwards, the solution B and the above solution A was mixed, agitated for 15 min at room temperature. After the agitation, the products were collected by centrifugation. And the precipitate was obtained by washing until the supernatant was colorless. Finally, the collected products were dried in an oven overnight to obtain the TB@CaCO3 composite. Preparation of TB@CaCO3@PAH and TB@CaCO3@PAH@DNA The TB@CaCO3 was added into PAH solution (1 mg·mL-1) for 20 min under continuous stirring. Then the products were centrifuged and washed with 10 mM of HEPES buffer (pH=7) for twice to obtain TB@CaCO3@PAH. The TB@CaCO3@PAH@DNA was synthesized as followings. The corresponding sequences of oligonucleotides were shown in Table S1 in the supporting information. Firstly, 15 mM of TB@CaCO3@PAH was coated by sequentially incubation in ssDNA strand A/Linker ssDNA L and ssDNA strand B/Linker L solutions, which is obtained by HEPES buffer (pH=7) with the ratio of A to L and B to L is 2 to 1, respectively. Each step was conducted for 30 min and repeated three times. After each step, the precipitate was washed to remove redundant nucleic acids. In this way, three DNA layers were coated on TB@CaCO3@PAH to obtain TB@CaCO3@PAH@DNA. Preparation of TB loading DNA microcapsules



When the DNA networks were assembled, EDTA solution (0.5 M, pH = 6) was subsequently dropped into the obtained TB@CaCO3@PAH@DNA product for 1 h under slow rotation. Then the supernatant solution was centrifuged for 3 times at 1500 rpm for 20 min and the product was washed with HEPES buffer to prevent the DNA microcapsule from aggregation. Afterwards, TB loading DNA microcapsules was obtained and dispersed in HEPES buffer before use. Preparation of SERS Substrates The prepared clean silicon wafer was immersed in 1 mL ethanol solution containing 3 % nafion for 1 h and dried to form Si@Nafion wafer. Then, the modified silicon wafer was immersed into AgNO3 solution (1 mL, 0.1 M), subsequently. After 30 min, the reducing agent (1 mL 0.1 M of NaBH4 and 1 mL 0.1 M of sodium citrate) were mixed with the above solution for another 30 min. Then AgNPs was dispersed on the wafer to form Si@Nafion@Ag. Finally, 3 µL of the above TB loading DNA microcapsules were added on the Si@Nafion@Ag. SERS Procedure The detailed fabrication process of the SERS biosensor was in Scheme 1. In details, 5 µL of DNA single strands C (100 µM) partly hybridize with single strands D (5 µL, 100 µM) in phosphate buffer solution (PBS) (10 µL, pH = 7.4) for 1 h at 37 °C. Nextly, different miRNA 155 concentrations were dropped into resulted solution to completely hybridize with DNA single strands C. Meanwhile, 5 µL of 0.05 U DSN was added in the above solutions under heating at 60ºC for 40 min. Then 2 µL of 75 mM EDTA was added to lead inactivation of the DSN for 10 min. Then the obtained products (ssDNA D) were dropped to the DNA microcapsule in the SERS substrate and kept the reaction 20 min at


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37 °C for opening DNA capsule to release TB. Lastly, the platform was measured by Raman microscope.

Results and Discussion Characterization

Figure 1. (A) TEM and (B) SEM of Ag NPs. The AgNPs is characterized by TEM and SEM in Figure 1A and Figure 1B, respectively. We can see that the Ag NPs are uniform with the size of about 30-40 nm. As shown in Figure 2A, TB@CaCO3 was uniform porous spheres with the size of about 1-2 µm. The porous structure may wrap more amount of TB in the co-precipitation process, resulting

enhanced

SERS

intensity.

Figure

2B

was

the

SEM

image

of

TB@CaCO3@PAH@DNA, we can easily find the size and morphology of spheres were mostly like CaCO3@TB except that the surface became bright, which is due to coating of DNA networks. After treated with the solution of EDTA, the CaCO3 core template was dissolved and left DNA capsule alone, so the morphology of CaCO3 disappeared and the origin spheres looked concave, thus the surface changed (Figure 2C).



Figure 2 SEM of (A) TB@CaCO3, (B) TB @CaCO3@ PAH@DNA, (C) TB loading DNA microcapsules. Principle of the SERS biosensor As shown in Scheme 1, the TB loading DNA microcapsule was obtained by LbL self-assembly with DNA strands. Because the dense DNA layer was locked, the Raman intensity of TB was quite weak (Scheme 1D, red curve). With the target miRNA155 induced DSN amplification, simulative target ssDNA D was released to complement with linker ssDNA L and open the DNA microcapsule. By this way, a small number of targets can produce plentiful ssDNA D and open a mass of DNA microcapsule. Then TB was released to the Ag NPs on the silicon wafer, leading to a high SERS intensity (Scheme 1D, blue curve). Based on this principle, the amount of miRNA was positively correlation with the amount of TB. The peak at 1627 cm-1 was chosen as the standard to quantitative detection of the target miRNA 155. Optimization of Assay Conditions DSN concentration is a key factor of the SERS platform, so we investigated the optimal concentration of DSN. As shown in Figure 3A, the Raman signal of TB enhanced with extending the concentration of DSN until 0.01 U. Thus, we chose 0.01 U (cmiRNA = 1 pM) as the best DSN concentration in this work. According to Figure 3B, when the


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incubation time of miRNA155 was 40 min, the Raman intensity could reach a pleateau value. Thus, 40 min (cmiRNA = 1 pM) was utilized to detect miRNA155.

Figure 3 SERS of the platform with different (A) DSN concentration and (B) incubation time of miRNA 155. (Error bar was calculated by 3 times test) Performance of the DNA microcapsule Based-SERS biosensor The detection of miRNA 155 by the SERS platform with elevated concentration was ranged from 1 fM-10 nM, which showed a gentle increase in the Raman signal at 1647 cm-1 (Figure 4A). As shown in Figure 4B, the detection limit of miRNA 155 was calculated as 0.64 fM according to the literature method27. The linear regression equation was y = 198.24 lgc + 61.529, with the correlation coefficient square (R2) of 0.9984 (y represented the Raman intensity at 1627 cm-1, c was the concentration of miRNA 155). The error bar was calculated by 3 times test for each concentration of miRNA 155. Compared with other works for assay of miRNA, this SERS platform based on DNA microcapsule provides a better performance to quantify miRNA 155 (Table 1).



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Figure 4 (A) SERS of the biosensor after incubation with the concentration of miRNA 155 from a to i: (a) 0, (b)103 aM, (c)104 aM, (d)105 aM, (e) 106 aM, (f) 107 aM, (g)108 aM, (h)109 aM, (i)1010 aM; (B) The linear curve of Raman intensity (1627 cm-1) with lgc. (Error bar was calculated by 3 times test)

Table 1. The performance of this prepared biosensor compared with other strategies for

detection of miRNA Analytical method

Target

Detection limit

Linear range

refs

Fluorescent

miRNA155

18 pM

0.02 nM-10 nM

28

Fluorescent

miRNA155

100 pM

0.1 nM-200 nM

29

Electrochemical

miRNA155

5.2 pM

0.01 nM-1.0 M

30

ECL

miRNA155

1.67 fM

5 fM-500 pM

31

SERS

miRNA122

0.24 pM

1 nM-1 pM

32

SERS

miRNA21

5 fM

12 fM-18 pM

33

SERS

miRNA155

0.64 fM

1 fM-1 nM

This work

Selectivity Other miRNAs were assessed as interference factors to investigate the selectivity of this biosensor. Due to the specific cleave effect of DSN, only complete complementary


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DNA-RNA hetero duplexes would be cleaved, which obviously improve the selectivity of SERS biosensor.34 As depicted in Figure 5, the blank sample and 100 pM of each interference (miRNA 141, miRNA 21,one-base mismatched DNA compared with target miRNA 155) all caused low Raman intensity. When the above three interferences (each was 100 pM) contained 1 pM miRNA 155 (mixture), the result showed no obvious difference with that obtained from 1 pM of miRNA 155 only. They all illustrated that in the presence of miRNA 155, the Raman intensity was much stronger than those of the other interferences, indicating the excellent selectivity of the biosensor for detection of miRNA 155.

Figure 5 SERS of biosensor with different solutions (The concentration of miRNA 155 is 1 pM, each interference is 100 pM, the mixture is 1 pM of miRNA 21 and 100 pM of three interferences). (Error bar was calculated by 3 times test) Reproducibility The reproducibility and the stability of the SERS-based biosensor were investigated by 15 different points of SERS spectra (cmiRNA 155 = 10 fM). According to Figure 6A, the SERS curves were mainly same and the relative standard deviation (RSD) of the SERS intensity at 1627 cm-1 was 7.46% (Figure 6B).



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Figure 6 (A) SERS of biosensor with 15 different spots; (B) The RSD of the intensity at 1627 cm-1 with 15 different spots. Application of the SERS Biosensor in Real Sample To further validate the feasibility and capability of the SERS platform, the recoveries were tested by this proposed biosensor. The miRNA 155 concentration in normal human serum (diluted 1000 times) were detected by the DNA microcapsule-based SERS Platform. From Table 2, the recoveries were from 93.9% to 101.4% and the RSD was between 0.4% and 2.2%, indicating that this biosensor could realize the effective application for miRNA 155 assay. Table 2. The detection results for different concentration of miRNA 155 in human serum (diluted 1000 times) Serum number

Added / fM

Found / fM

Recovery / %

RSD / %

(n = 3) 1

1

0.9795

97.9

1.9

2

100

10.14

101.4

2.2

3

1000

100.7

100.7

0.4

4

10000

939.7

93.9

2.0

5

100000

10092

100.9

1.1


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Conclusions In this work, one DNA microcapsules was constructed through LbL self-assembly of DNA strands crosslinked by linker ssDNA L. With target miRNA 155 induced DSN signal amplification, large amount of simulative target ssDNA D were obtained. Due to the complete complementary of ssDNA D and linker ssDNA L on the DNA capsule, the DNA microcapsule would be destroyed to released TB, realizing a high Raman signal. By combining this DNA microcapsule and target miRNA 155 induced DSN amplification strategy, this SERS platform could achieve a liner range from 1 fM to 10 nM and a detection limit of 0.67 fM for miRNA 155. This work can achieve the easy assembling of DNA capsule and rapid response to trace miRNA, which can be expanded to other programmable DNA microcapsules for miRNA detection, further supply one new strategy for biosensing and clinic diagnosis. Acknowledgment This work was supported by the NNSF of China (51602263), China Postdoctoral Science Foundation (2015M572427, 2016T90827) and Chongqing Postdoctoral Research Project (xm2015019). ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge via the Internet at http://pubs.acs.org/. The sequences of oligonucleotides in the experiment, Material and Reagents, Apparatus.



References [1] Ma, W.; Fu, P.; Sun, M. Z.; Xu, L. G.; Kuang, H.; Xu. C. L. Dual Quantification of MicroRNAs and Telomerase in Living Cells. J. Am. Chem. Soc. 2017, 139, 11752−11759. [2] Duan, R. X.; Zhang, Z. Y.; Zheng, F. X.; Wang, L. W.; Guo, J.; Zhang, T. C.; Dai, X. M.; Zhang, S.W.; Yang, D.; Kuang, R. R.; Wang, G. X.; He, C. H.; Hakeem, A.; Shu, C.; Yin, P.; Lou, X. D.; Zeng, F. Q.; Liang, H. G.; Xia, F. Combining Protein and miRNA Quantification for Bladder Cancer Analysis. ACS Appl. Mater. Interfaces 2017, 9, 23420-23427. [3] Zhang, P.; Lin, Z. F.; Zhuo, Y.; Yuan, R.; Chai, Y. Q. Dual microRNAs-Fueled DNA Nanogears: A Case of Regenerated Strategy for Multiple Electrochemiluminescence Detection of microRNAs with Single Luminophore. Anal. Chem. 2017, 89, 1338-1345. [4] He, M. Q.; Wang, K.; Wang, W. J.; Yu, Y. L.; Wang, J. H. Smart DNA Machine for Carcinoembryonic Antigen Detection by Exonuclease III-Assisted Target Recycling and DNA Walker Cascade Amplification. Anal. Chem. 2017, 89, 9292−9298. [5] Yu, Y. Y.; Chen, Z. G.; Shi, L. J.; Yang, F.; Pan, J. B.; Zhang, B. B.; Sun, D. P. Ultrasensitive Electrochemical Detection of MicroRNA Based on an Arched Probe Mediated Isothermal Exponential Amplification. Anal. Chem. 2014, 86, 8200-8205. [6] He,Y.; Wang, Y.; Yang, X.; Xie, S. B.; Yuan, R.; Chai, Y. Q. Metal Organic Frameworks Combining CoFe2O4 Magnetic Nanoparticles as Highly Efficient SERS Sensing Platform for Ultrasensitive Detection of N-Terminal Pro-Brain Natriuretic Peptide. ACS Appl. Mater. Interfaces 2016, 8, 7683−7690. [7] Kauppinen, S.; Valoczi, A.; Hornyik, C.; Varga, N.; Burgyan, J.; Havelda, Z. Sensitive


Page 14 of 19

Page 15 of 19 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


and Specific Detection of MicroRNAs by Northern Blot Analysis using LNA-modified Oligonucleotide Probes. Nucleic Acids Res. 2004, 32, e175. [8] Peng, Y. F.; Yi, G. S.; Gao, Z. Q. A Highly Sensitive microRNA Biosensor based on Ruthenium Oxide Nanoparticle-initiated Polymerization of Aniline. Chem. Commun. 2010, 46, 9131-9133. [9] Duan, R. X.; Zuo, X. L.; Wang, S. T.; Quan, X. Y.; Chen, D. L.; Chen, Z. F.; Jiang, L.; Fan, C. H.;

Xia, F.

Lab in a Tube: Ultrasensitive Detection of microRNAs at the

Single-cell Level and in Breast Cancer Patients using Quadratic Isothermal Amplification. J. Am. Chem. Soc. 2013, 135, 4604-4607 [10] Pang, Y. F.; Wang, C. W.; Wang, J.; Sun, Z. W.; Xiao, R.; Wang, S. Q. Fe3O4@Ag Magnetic Nanoparticles for microRNA Capture and Duplex-specific Nuclease Signal Amplification based SERS Detection in cancer cells. Biosens.Bioelectron. 2016, 79, 574-580 [11] Majumdar, D.; Singha, A.; Mondal, P. K.; Kundu, S. DNA-Mediated Wirelike Clusters of Silver Nanoparticles: An Ultrasensitive SERS Substrate. ACS Appl. Mater. Interfaces, 2013, 5, 7798–7807. [12] Yu, A. M.; Wang, Y. J.; Barlow, E.; Caruso, F. Mesoporous Silica Particles as Templates for Preparing Enzyme-Loaded Biocompatible Microcapsules. Adv. Mater. 2005, 17, 1737-1741. [13] Kreft, O.; Prevot, M.; Mhwald, H.; Sukhorukov, G. B. Shell-in-Shell Microcapsules: A Novel Tool for Integrated, Spatially Confined Enzymatic Reactions. Angew. Chem. Int. Ed. 2007, 46, 5605-5608 [14] Price, A. D.; Zelikin, A. N.; Wang, Y. J.; Caruso, F. Shell-in-Shell Microcapsules: A



Page 16 of 19

Novel Tool for Integrated, Spatially Confined Enzymatic Reactions. Angew. Chem. Int. Ed. 2009, 48, 329-332 [15] Huang, F. J.; Liao, W. C.; Sohn, Y. S.; Nechushtai, R.; Lu, C. H.; Willner, I. Light-Responsive and pH-Responsive DNA Microcapsules for Controlled Release of Loads. J. Am. Chem. Soc. 2016, 138, 8936−8945 [16] Liao, W. C.; Riutin, M.; Parak, W. J.; Willner, I. Programmed pH-Responsive Microcapsules for the Controlled Release of CdSe/ZnS Quantum Dots. ACS Nano 2016, 10, 8683-8689. [17] Guo, W.; Qi, X. J.; Orbach, R.; Lu, C. H.; Freage, L.; Mironi-Harpaz, I.; Seliktar, D.; Yang, H.H.; Willner, I. Reversible Ag+-crosslinked DNA hydrogels. Chem. Commun. 2014, 50, 4065-4068. [18] Xu, W. N.; Choi, I.; Plamper, F. A.; Synatschke, C. V.; Mu¨ller, A.H. E.; Tsukruk,V. V. Nondestructive Light-Initiated Tuning of Layer-by-Layer Microcapsule Permeability. ACS Nano, 2013, 7, 598-613. [19] Guo, W.; Lu, C. H.; Qi, X. J.; Orbach, R.; Fadeev, M.; Yang, H. H.; Willner, I. Switchable Bifunctional Stimuli-Triggered Poly-N-Isopropylacrylamide/DNA Hydrogels. Angew. Chem., Int. Ed. 2014, 53, 10134-10138. [20] Johnston, A. P.; Lee, L.; Wang, Y.; Caruso, F. Controlled Degradation of DNA Capsules with Engineered Restriction-Enzyme Cut Sites. Small, 2009, 5, 1418-1421. [21] Liao, W. C.; Lu, C. H.; Hartmann, R.; Wang, F.;

Sohn, Y.S.; Parak, W. J.;

Willner, I. Adenosine Triphosphate-Triggered Release of Macromolecular and Nanoparticle Loads from Aptamer/DNA-Cross-Linked Microcapsules. ACS Nano, 2015, 9, 9078-9086.


Page 17 of 19 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


[22] Liao, W. C.; Sohn, Y. S.; Riutin, M.; Cecconello, A.; Parak, W. J.; Nechushtai, R.; Willner, I. The Application of Stimuli-Responsive VEGF- and ATP-Aptamer-Based Microcapsules for the Controlled Release of an Anticancer Drug, and the Selective Targeted Cytotoxicity toward Cancer Cells. Adv. Funct. Mater. 2016, 26, 4262-4273. [23] He, Y.; Yang, X.; Yuan, R.; Chai, Y. Q. Switchable Target-responsive 3D DNA Hydrogels as a Signal Amplification Strategy Combining with SERS Technique for Ultrasensitive Detection of miRNA 155. Anal. Chem., 2017, 89, 8538-8544. [24] Borodina, T.; Markvicheva, E.; Kunizhev, S.; Mo¨hwald, H.; Sukhorukov, G. B.; Kreft. O. Controlled Release of DNA from Self-Degrading Microcapsules. Macromol. Rapid Commun. 2007, 28, 1894–1899 [25] Liao, W. C.; Lilienthal, S.; Kahn, J.S.; Riutin, M.; Sohn, Y.S. ; Nechushtai, R.; Willner, I. PH- and Ligand-induced Release of Loads from DNA–acrylamide Hydrogel Microcapsules. Chem. Sci. 2017, 8, 3362–3373. [26] Wang, Y. S.; Moo, Y. X.; Chen, C. P.; Gunawan, P.; Xu, R. Fast Precipitation of Uniform CaCO3 Nanospheres and their Transformation to Hollow Hydroxyapatite Nanospheres. J. Colloid. Inter., 2010, 352, 393-400. [27] Radi, A. E.; Sánchez, J. L. A.; Baldrich, E.; O’Sullivan, C. K. Reagentless, Reusable, Ultrasensitive Electrochemical Molecular Beacon Aptasensor. J. Am. Chem. Soc. 2006, 128, 117-124. [28] Liu, Y. J.; Wei, M.; Li, Y.; Liu, A.; Wei, W.; Zhang, Y. J.; Liu, S. Q. Application of Spectral Crosstalk Correction for Improving Multiplexed MicroRNA Detection Using a Single Excitation Wavelength. Anal. Chem. 2017, 89, 3430-3436. [29] Zhang, H.; Wang, Y. S.; Zhao, D. W.;

Zeng, D. D.; Xia, J. Y.; Aldalbahi, A.; Wang,



C. G.; San, L.; Fan, C. H.; Zuo, X. L.; Mi, X. Q. Universal Fluorescence Biosensor Platform Based on Graphene Quantum Dots and Pyrene-Functionalized Molecular Beacons for Detection of MicroRNAs. ACS Appl. Mater. Interfaces 2015, 7, 16152-16156. [30] Kong, D. Q.; Bi, S. Z.; Wang, H.; Xia, J. F.; Zhang, F. F. In Situ Growth of Three-Dimensional Graphene Films for Signal-On Electrochemical Biosensing of Various Analytes. Anal. Chem. 2016, 88, 10667-106742 [31] Peng, L. C.; Zhang, P.; Chai, Y. Q.; Yuan, R. Bi-directional DNA Walking Machine and Its Application in an Enzyme-Free Electrochemiluminescence Biosensor for Sensitive Detection of MicroRNAs. Anal. Chem. 2017, 89, 5036-5042 [32] Zhou, W.; Tian, Y. F.; Yin, B. C.; Ye, B. C. Simultaneous Surface-Enhanced Raman Spectroscopy Detection of Multiplexed MicroRNA Biomarkers. Anal. Chem. 2017, 89, 6120−6128. [33] Ma, D. D.; Huang, C. X.; Zheng, J.; Tang, J. R.; Li, J. S.; Yang, J. F.; Yang, R. H. Quantitative Detection of Exosomal microRNA Extracted from Human Blood based on Surface-enhanced Raman Scattering. Biosen. Bioelectron. 2018, 101,167–173. [34] Yin, B. C.; Liu, Y. Q.; Ye, B. C. One-Step, Multiplexed Fluorescence Detection of microRNAs Based on Duplex-Specific Nuclease Signal Amplification. J. Am. Chem. Soc. 2012, 134, 5064-5067.


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Stimuli-responsive DNA Microcapsules for SERS Sensing of Trace

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