Au Heterostructured

Research Article pubs.acs.org/journal/ascecg

Cite This: ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

Photochemical Synthesis of Porous CuFeSe2/Au Heterostructured Nanospheres as SERS Sensor for Ultrasensitive Detection of Lung Cancer Cells and Their Biomarkers Huang Wen,† Hao Wang,† Jun Hai, Suisui He, Fengjuan Chen, and Baodui Wang* State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou 730000, People’s Republic of China

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S Supporting Information *

ABSTRACT: Rapid and sensitive identification of tumor biomarker or cancer cells in their nascent stage based on surface-enhanced Raman scattering (SERS) is still an attractive challenge due to the low molecular affinity for the metal surface, the complexity of the sample, and low-efficiency use of hot spots in one- or two-dimensional geometries. Here, we demonstrated a novel kind of renewable CuFeSe2/Au heterostructured nanospheres that are hierarchically porous for specific and sensitive detection of lung cancer biomarkers of aldehydes and lung cancer cells. The heterostructured nanospheres were constructed by loading an Au shell formed by photoreduction on the CuFeSe2 frameworks. P-aminothiophenol (4-ATP) as a Raman-active probe molecule was first grafted on CuFeSe2/Au nanospheres, and then the gaseous aldehyde molecules were sensitively bonded onto the nanospheres by formation of a CN bond with a detection limit of 1.0 ppb. Moreover, the resulting folic acid (FA)-conjugated nanospheres have a high SERS activity to Rhodamine B isothiocyanate (RBITC), which can be used to specifically recognize and sensitively detect the A549 cells. Our study suggested that the synthesized renewable CuFeSe2/Au heterostructured nanospheres as a multimodal platform could find a wide range of applications in the fields of medicine, biotechnology, and environmental sciences. KEYWORDS: SERS, Biosensing, Lung cancer biomarkers, Multifunctional nanoplatform, Volatile organic compounds, Cancer diagnosis

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to cell senescence.16 Therefore, there is a pressing need to develop new methods with sensitive signal expression and specific biological characteristics for diagnosis of lung cancer. SERS has become a powerful tool for biological analysis because of its high selectivity, high sensitivity, and fluorescence-quenching properties. SERS enhancement originates from two main mechanisms: (i) the electromagnetic fields produced near the surface of nanostructures and (ii) the charge-transfer states generated between the metal and the analyte adsorbed to the surface of metal.17,18 In this sense, enhancement of both electromagnetic and chemical mechanisms needs to have a close proximity of the analyte toward the metal surface.19 Recently, Au nanostructures are attractive SERS substrates due to its unique thermal, optical, and electronic properties.20−26 Generally, the morphology of gold has a significant impact on its SERS activity.27,28 For example, the latest

INTRODUCTION Lung cancer is the most common cancer in the world with a 5 year survival rate of 15%.1 Like many other diseases, developing early diagnosis assays with sensitivity and selectivity is an urgent requirement and necessary for improving cancer therapy. In general, it is essential to identify the sensitive and specific biomarkers of early lung cancer. Volatile organic compounds (VOCs), which are important markers of lung cancer, belong to the Raman-inactive molecules.2 When the levels of these VOCs reach between 10 and 100 ppb they can be identified as biomarkers of lung cancer.3,4 In many lung cancer markers aldehydes in exhaled breath are important indicators of lung cancer because oxidative stress as well as tumor-specific tissue composition and metabolism contain such substances.2,5 To date, several analytical techniques have been used to detect VOCs, including gas chromatography/mass spectrometry,6,7 ion migration spectroscopy,8,9 selected ion flow tube mass spectrometry,10,11 chemical sensors,12 and SERS.13−15 Usually, due to the teratogenicity, carcinogenicity, genotoxicity, and mutagenicity of glyoxal, only 1 ppm glyoxal can lead © XXXX American Chemical Society

Received: November 23, 2018 Revised: January 28, 2019 Published: February 11, 2019 A

DOI: 10.1021/acssuschemeng.8b06116 ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

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ACS Sustainable Chemistry & Engineering

Scheme 1. (A) Schematic Drawing of a Proposed New Crystal Growth Route of CuFeSe2/Au Nanospheres; (B) Schematic Illustration of the Strategy To SERS Detect Gaseous Aldehydes and A549 Cells

research shows that nanostructured Au with a rich “hot spot” is beneficial for SERS.29−31 Moreover, with very high enhancement factors obtained from the hot spots between the dimer and the trimer of a nanoparticle and the edge/corner of nanoparticles (NPs), more and more efforts have been focused on establishment of dealloyed nanoporous metals to improve signal stability, reproducibility, and practical operation.32−39 Such unique characteristics are not only beneficial to the excitation of the local surface plasma but also offer a great deal of molecular binding sites. However, when these nanoporous metals are used as substrates to detect single molecules, the SERS signal is either poorly repeatable or inadequate. The main reason is due to the limitation of control over the structural parameters such as pore geometry and order.33 In addition, in order to improve the usage rate of the sensor, development of renewable sensors with photocatalytic activity is urgently needed.40 Moreover, recent research shows that plasmatic core−shell nanomaterials are easy to functionalize and can be used to improve the sensitivity of SPR sensors.41,42 On the basis of the above considerations, we envisage that construction of renewable core−shell nanomaterials should improve the sensitivity of detection. In this study, we prepared hierarchical porous CuFeSe2/Au heterostructured nanospheres by a simple photoreduction method for detecting typical lung cancer biomarkers of aldehydes and lung cancer cells. As shown in Scheme 1, the nanoplatform was constructed by loading a gold shell onto the CuFeSe2 nanocrystals (NCs) surface under NIR light irradiation, forming core−shell CuFeSe2/Au heterostructured nanospheres. Because there are many cavity traps on the surface of the nanospheres, the gaseous aldehydes undergo the

“cavity vortex effect” through the nanospheres surface (Figure 1C and 1D), which increases the reaction time of gases on the surface.43,44 When the aldehydes reacted with the4-ATP via nucleophilic addition and bounded on CuFeSe2/Au nanospheres, the SERS signal of 4-ATP changed obviously, with a detection limit of 1 ppb. Moreover, the as-prapared nanospheres modified with folic acid (FA) exhibit excellent SERS active to Rhodamine B isothiocyanate (RBITC), which can be used as a dual-mode biosensor for SERS-based detection of folate receptor (FR)-positive cancer cells with high selectivity and sensitivity. Moreover, such CuFeSe2/Au SERS substrate exhibits high photocatalytic regeneration efficiency by photocatalytic degradation of the adsorbed probes or biomolecules, respectively. This work is the first report that used the renewable nanoprobes to detect cancer markers.

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EXPERIMENTAL SECTION

Materials. Chloroauric acid (HAuCl4·4H2O, 47%) and 4-aminothiophenol (4-ATP, 98%) were obtained from Energy Chemical (Shanghai, China). Copper(II) acetylacetonate (Cu(acac)2, 99.99%), iron(III) acetylacetonate (Fe(acac)3, 99.9%), diphenyl diselenide (98%), oleylamine (70%), 3,4-dihydroxybenzaldehyde, and diphenyl ether were purchased from Sigma-Aldrich. All chemicals were used without further purification. HS-PEG-NH2 and HS-PEG-NH-FA were prepared according to a reported method.45 Characterization. SERS spectra were recorded on a Renishaw confocal microscope Raman system with an excitation source of 785 nm. Scanning electron microscopy (SEM) images were obtained on a field-emission scanning electron microscope (S4800). Transmission electron microscopy (TEM) experiments were performed on a JEM2100 TEM operating at a voltage of 200 kV. UV−vis spectra were obtained via a Shimadzu UV-1750 spectrophotometer. The powder X-ray diffraction (XRD) was investigated by a Bruker D8-Advance B


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Photoinduced Synthesis of CuFeSe2/Au Nanospheres. A mixed solution consisting of 0.1 mmol of HAuCl4·4H2O (413 mg) in ethanol (10 mL) and 10 mg of CuFeSe2 frameworks in ethanol (10 mL) was irradiated under the Xe lamp (λ > 850 nm) for 120 min at 20 °C; the product was obtained and dispersed in ethanol after centrifuging and washing with ethanol three times.

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RESULTS AND DISCUSSION Preparation and Characterization of CuFeSe2/Au Nanospheres. As shown in Scheme 1A, synthesis of CuFeSe2/Au nanospheres involves three steps. First, CuFeSe2 NCs were prepared by thermal decomposition. The TEM image of the obtained CuFeSe2 NCs shows that the morphology has a uniform and monodisperse spherical shape (Figure 1A), as the size of the as-prepared CuFeSe2 NCs measured from the TEM images are ∼5.7 nm size, and the corresponding size distribution histogram is presented in the Supporting Information (Figure S1). The HRTEM image clearly shows a d spacing of 0.272 nm (Figure S2), corresponding to the (200) planes of the CuFeSe2 in tetragonal phase.46 XRD analysis (Figure 2A) provides that

Figure 1. (A) TEM image of CuFeSe2 NCs. (B) TEM image of CuFeSe2 frameworks. (C) Low-resolution SEM image of CuFeSe2/Au nanospheres. (D) High-resolution SEM image of CuFeSe2/Au nanospheres. (E) High-angle annular dark-field scanning TEM (HAADF-STEM). (F) Element mapping images of CuFeSe2/Au nanospheres. using Cu Kα radiation (l = 1.5418 Å). All samples were analyzed in a PHI-5702 XPS with a monochromatic Al Kα source. Photoreduction was performed using a xenon lamp (HSX-F300). A Fourier transforminfrared (FT-IR) spectrometer (Bruker Vertex 70) with a singlereflectance ATR accessory was used for acquiring IR spectra. The chemical composition of the nanostructures was measured by inductively coupled plasma atomic emission (ICP-AES). Synthesis of CuFeSe2 NCs. First, 15 mL of oleylamine (OAm, 70%), 15 mL of diphenyl ether, Fe(acac)3 (0.706 g, 2 mmol), and Cu(acac)2 (0.262 g, 1 mmol) were added to a round-bottom flask (100 mL) and then stirred under a flow of nitrogen for 15 min. After dehydrating at 110 °C for 90 min in N2 atmosphere, the solution was heated up to 265 °C and kept for 60 min. Second, 1 mL of oleylamine containing 1 mmol of diphenyl diselenide was added into the flask by a syringe quickly. The reaction is over after 60 min. Finally, the CuFeSe2 NCs were dispersed in chloroform after centrifuging with ethanol three times. Synthesis of 4,4′-((1E,11E)-2,5,8,11-Tetraazadodeca-1,11diene-1,12-diyl)bis(benzene-1,2-diol)(DIB-TETA). In a typical sythesis, 10 mg of triethylenetetramine in 10 mL of ethanol was slowly added into a solution consisting of 200 mg of 3,4dihydroxybenzaldehyde in 10 mL of ethanol. After the solution reacted at 25 °C for 24 h, the product was obtained by centrifuging and washing with ethanol several times. Synthesis of CuFeSe2 Frameworks. After a mixture containing 15 mg of DIB-TETA dissolved in DMSO (10 mL) and 0.01 g of CuFeSe2 NCs dispersed in 10 mL of CHCl3 was stirred overnight at 25 °C, the product was obtained and dispersed in ethanol after centrifuging and washing with ethanol and petroleum ether (1:2 V/V) serveral times.

Figure 2. XRD patterns of (A) CuFeSe2 NCs (blue), CuFeSe2 frameworks (black), and JPCDS No.81-1959 of CuFeSe2 NCs (red). (B) CuFeSe2/Au nanospheres and (inset) XRD patterns of the expanded view for the rectangle in red showing the (112) and (200) crystal faces of CuFeSe2 NCs. XPS spectra of CuFeSe2/Au nanospheres: (C) survey; (D) Cu 2p; (E) Fe 2p; (F) Au 4f.

all of the diffraction peaks can be well indexed to the standard data of CuFeSe2 (JCPDS file no. 81-1959).47 Moreover, ICPAES (Table S1) and XPS (Figure S4) were used to obtain the element ratio and oxidation states of the CuFeSe2 NCs. Second, CuFeSe2 NCs and DIB-TETA coordinate assembly into CuFeSe2 frameworks. The TEM image indicates that mesopores with different pore sizes, which are not found in CuFeSe2 NCs (Figure 1A), appeared after the CuFeSe2 NCs reacted with DIB-TETA (Figure 1B). Furthermore, the XRD C


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Figure 3. SERS detection of the gaseous aldehydes: (A) Typical Raman spectral of the 4-ATP on CuFeSe2/Au nanospheres before (red) and after (blue) reacted with benzaldehydes. SERS mapping of the Raman intensity of CN peaks at 1616 cm−1 (B) without the concentration of the gaseous benzaldehydes and (C) with the concentration of the gaseous benzaldehydes. The specified area: 208 measuring points. (D) The plot of the Raman Intensity of CN peaks at 1616 cm−1 with the concentration of the gaseous benzaldehydes (E) Raman spectra of the glyoxal, glutaraldehyde, benzaldehyde, and phenylacetaldehyde at the concentrations of 1.0 ppb. (F) Selectively detection of the aldehyde to other potential interfering lung cancer biomarkers, including the hydrocarbon (n-hexane, cyclohexane), the alcohol (methyl alcohol, ethyl alcohol), the ketone (acetone, butanone), the ester (butyl acetate), the nitrile (acetonitrile), and the aromatic compound (methylbenzene).

nanospheres to 398.34 eV for CuFeSe2−Frameworks is due to N atoms coordination with Au (11A).49 Similarly, the Se peaks upshift from 55.21 eV for CuFeSe2 frameworks to 55.69 eV for CuFeSe2/Au nanospheres also reveals the coordination between the Se element and the Au nanospheres (Figure S11B).50 As seen in the FT-IR spectra (Figure S12), the peak of the N−H groups downshift from 3420 cm−1 of CuFeSe2 frameworks to 3409 cm−1 for CuFeSe2/Au nanospheres, indicating coordination between N−H groups of CuFeSe2− Frameworks and Au0.51 Similarly, the peak of the vibrations (CN groups) upshifts from 1647 cm−1 for CuFeSe2/Au nanospheres to 1657 cm−1 for CuFeSe2−Frameworks because of the coordination of CuFeSe2 frameworks (CN groups) and Au0.52 Meanwhile, the peak for the group of Au−N is located at 414 nm.53 Furthermore, to explore the growth mechanism of CuFeSe2/ Au nanospheres, a time-dependent growth process was monitored by SEM (Figure S13), and the experimental results and related discussion are given in the Supporting Information. We also found that the amount of HAuCl4·4H2O plays an important role in the growth of CuFeSe2/Au nanospheres (Figure S14). Detailed information is given in the Supporting Information. SERS Detection of Aldehyde Molecules Based on CuFeSe2/Au Nanospheres. As the “cavity-vortex” effect of the CuFeSe2/Au nanostructures could enhance the adsorptivity of gases, we used the CuFeSe2/Au nanospheres to detect aldehyde molecules. Because the molecules with polar bonds (CO) have relatively small Raman cross sections, aldehyde molecules cannot be sensitively identified by SERS. Here, 4ATP molecules were used as a bridge to bond gaseous aldehydes (Scheme 1B). Due to the strong coordination between the thiol group and the gold,54 4-ATP could be easily adsorbed on the CuFeSe2/Au nanospheres surface (Figure 3A) but is hardly adsorbed on the CuFeSe2 NCs surface (Figure S15). The peaks appear at 1003, 1067, 1138, 1386, 1437, and

pattern of assembled CuFeSe2 frameworks also coincides well with those of standard CuFeSe2 (JCPDS file no. 81-1959, Figure 2A). In addition, the XPS measurementsS (Figures S5 and S6) and FT-IR spectrum (Figure S7) monitored the formation of CuFeSe2 frameworks. Finally, CuFeSe2/Au nanospheres were synthesized by deposition of the Au shell on the surface of CuFeSe2 NCs through irradiating with a NIR light (λ > 850 nm). SEM images (Figure 1C and 1D) indicated that the CuFeSe2/Au nanostructures are spherical, and the surface of the nanostructure is stacked by a lot of nanoparticles, forming a lot of holes. From the element mappings of CuFeSe2/Au nanospheres (Figure 1E and 1F), Au is present on the outside of the nanospheres and four elements exist in the whole testing area, which indicate that the distribution of CuFeSe2 NCs is homogeneous in the gold shell. Also, the EDX spectra show the presence of Se, Au, Cu, and Fe elements in CuFeSe2/Au nanospheres (Figure S8). The whole absorbance of CuFeSe2/ Au heterostructured nanospheres is demonstrated in Figure S9. As shown in Figure 2B, the Au core exhibits a strong peak in the nanostructures, and the inset XRD patterns of the expanded view show two crystal faces (112) and (200) of CuFeSe2 NCs. The weak diffraction intensity further indicates that CuFeSe2 NCs were encapsulated in the gold shell. The XPS survey spectrum indicates the presence of C, N, O, Fe, Cu, Se, and Au (Figure 2C). Peaks at 931.97 and 953.65 eV can be observed, which are assigned to Cu+ 2p3/2 and Cu+ 2p1/2, respectively (Figure 2D). Meanwhile, the shake-up structure of copper(II) confirms the existence of little Cu2+. Also, two peaks at 711.35 and 722.45 eV indicate the presence of Fe3+ (Figure 2E). The characteristic peaks of Au0 4f for CuFeSe2/Au nanospheres are at 84.42 and 88.07 eV (Figure 2F).48 The peaks at 531.70 and 398.69 eV are attributed to O 1s (Figure S10A) and N 1s (Figure S10B), respectively. The Se peaks is assigned to 55.69 eV (Figure S10C). Furthermore, the down shift of the N 1s from 398.69 eV for CuFeSe2/Au D


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Figure 4. (A) Raman spectra of the 4-ATP (10 ppb) on the CuFeSe2/Au nanospheres for different collection times on the gaseous 4-ATP. (B) SERS detection of the gaseous benzaldehydes under different moisture. (C) Detection of the benzaldehyde in the presence of other potential interfering lung cancer biomarkers (red), including hydrocarbons (n-hexane (20 μL) and cyclohexane (20 μL)), alcohols (methyl alcohol (20 μL) and ethyl alcohol (20 μL)), ketones (acetone (20 μL) and butanone (20 μL)), esters (butyl acetate (20 μL)), nitriles (acetonitrile (20 μL)), and aromatic compounds (methylbenzene (20 μL)). Lower SERS spectrum (black) was the corresponding 4-ATP reacted with the gaseous benzaldehyde directly on the CuFeSe2/Au nanospheres.

Figure 5. (A) SERS spectra of the CuFeSe2/Au nanospheres with RBITC (red) and without RBITC (black). (B) SERS mapping image of the RBITC 1648 cm−1 peak on CuFeSe2/Au nanospheres after being incubated with the RBITC. Specified area: 208 measuring points.

1571 cm−1, which are consistent with the experimental results reported previously (Table S2).55 When the −CHO group of benzaldehydes and the −NH2 group of 4-ATP grafted on CuFeSe 2 /Au nanospheres form a −CN− group, a prominent peak at 1616 cm−1 was observed in the Raman sprctra (Figure 3A). In addition, the strong vibration (1065 cm−1) of the phenyl ring moves to high frequency (1073 cm−1) due to the pion electron conjugation between the two phenyl rings via the C N bridging group. At same time, the bend or deformation mode of C−H and N−H appeared at 1231 cm−1. SERS mapping of the Raman intensity of the CN peaks at 1616 cm−1 without or with the 1.0 ppb benzaldehydes vapor further indicated formation of a −CN− group (Figure 3B and 3C). With the increasing concentration of benzaldehydes, the Raman intensity gradually increases and a good linear relationship in the range of 1.0−10.0 ppm is obserbed (Figures 3D and S16). The limit of detection is at 1 ppb, which is lower than the other reported method (Table S3).15,56 Moreover, other aldehydes molecules, such as gaseous, glutaraldehyde, phenylacetaldehyde, and glyoxal, can be sensitively identified at 1.0 ppb (Figures 3E and S17). In order to prove the selectivity of this method, other potential interfering lung cancer biomarkers, including hydrocarbons (n-hexane, cyclohexane), alcohols (methyl alcohol, ethyl alcohol), ketones (acetone, butanone), esters (butyl acetate), nitriles (acetonitrile), and aromatic compounds (methylbenzene), were also detected. As shown in Figure 3F,

no CN peak at 1616 cm−1 was observed, indicating that this method exhibits excellent selective detection of the aldehydes. We used SERS to track the adsorbed amount of 10 ppb 4ATP vapor on the nanostructure at different times of 5, 10, 20, 40, and 80 min. As shown in Figure 4A, when the adsorption time reaches 5 min, a characteristic Raman peak of 4-ATP at 1067 cm−1 begins to be easily observed. When the adsorption reaction reached 40 min, the peak strength of the C−C symmetric stretch ring breathing at 1003 cm−1 tends to slowly pace down. In addition, the presence of water molecules hardly affects the sensitivity of this method to gaseous aldehydes (Figure 4B). Moreover, aldehydes can be clearly distinguished from mixtures of other substances with target aldehydes, providing a practical potential platform for aldehydes sensing in clinical diagnostics. Feasibility of FA-CuFeSe2/Au Nanospheres for Cancer Cell Detection. The CuFeSe2/Au nanospheres with a rough surface also inspired us to investigate their other applications by using their SERS activities. Under a 532 or 633 nm laser, the CuFeSe2/Au heterostructured nanospheres did not show any SERS signal (Figure S18); therefore, we chose a 785 nm laser for SERS detection. In addition, RBITC was used as the probe molecule. As shown in Figure 5A, distinct SERS peaks of RBITC molecules were seen at 621, 1201, 1277, 1358, 1505, and 1648 cm−1, which is consistent with the previously reported results (Table S2).57 The calculated analytical enhancement factor (AEF) value of the CuFeSe2/Au nanospheres based on eq 1 was ∼2.98 × 106 (detailed information E


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Figure 6. (A) SERS spectra of the A549 cells with RBITC (blue) and with FA-conjugated CuFeSe2/Au nanospheres (black). SERS spectra of the NIH3T3 and A549 cells (red and pink) after being incubated with the RBITC-labeled FA-conjugated CuFeSe2/Au nanospheres. (B) SERS mapping images of the RBITC 1648 cm−1 peak on A549 cells after being incubated with the RBITC-labeled FA-conjugated CuFeSe2/Au nanospheres. Specified area: 208 measuring points.

that incubated with the FA-CuFeSe2/Au nanospheres labeled with RBITC (red). The SERS mapping image of the RBITC 1648 cm−1 peak on A549 cells demonstrates the homogeneous and stronger Raman enhancement of RBITC on the CuFeSe2/ Au nanospheres (Figure 6B). These results suggested that the SERS strategy based on FA-CuFeSe2/Au nanospheres can be applied for detecting the FA-positive expressed cancer cells. Moreover, the heterostructured nanospheres have high stability in the cell culture medium (Figure S24).

in Figure S19), which is higher than other reported substrates.57−59 These results indicated that the substrate of CuFeSe2/Au nanospheres has superior SERS activity. In addition, no Raman peaks were observed in CuFeSe2/Au nanospheres alone, indicating no interference to the test of RBITC. Moreover, the SERS mapping image of the RBITC 1648 cm−1 peak in Figure 5B demonstrates the homogeneous and stronger Raman enhancement on the CuFeSe2/Au nanospheres. In our previous studies we demonstrated that the twodimensional (2D) core−shell CuFeSe2@Au heterostructured nanosheet displays excellent photocatalytic activity and high stability for water oxidation. Here we chose CuFeSe2/Au nanospheres to test its recyclable capacity. As shown in Figure S20, the CuFeSe2/Au nanospheres show SERS signal of Rhodamine6G (R6G) when CuFeSe2/Au substrate was immersed in RBITC solution for 12 h. However, when the visible light irradiated the CuFeSe2/Au substrate for 1 h, the SERS signal of R6G is barely detectable because of the degradation of such molecules, and the signal can be recovered after being immersed in R6G solution again. These results indicate that the CuFeSe2/Au nanospheres could provide efficient renewable properties by photodegrading undesired adsorbed biomolecules. On the basis of the high SERS signal of RBITC on the surface of nanospheres, FA-CuFeSe2/Au nanosphere-labeled RBITC was used to specifically detect the FR-overexpressing A549 cells caused by the specific interaction between FA and FR (Scheme 1B). In order to improve the biocompatibility and targeting of nanospheres, CuFeSe2/Au nanospheres were modified with HS-PEG-NH2 and HS-PEG-NH-FA. The resulting FA-CuFeSe2/Au nanospheres were characterized by UV−vis spectra (Figure S21). Cytotoxic experiments suggested that the CuFeSe2/Au nanospheres have low cytotoxicity (Figure S22). As shown in Figures 6A and S23, only when FA-CuFeSe2/ Au nanospheres labeled with RBITC interacted with A549 cells did we observe the characteristic peaks of RBITC in the SERS spectrum (pink). However, when A549 cells were only cultured with RBITC or CuFeSe2/Au nanospheres, no RBITC signal was found (spectra blue and black). In addition, no SERS signal of the RBITC was observed in the NIH3T3 cells

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CONCLUSION In summary, for the first time a renewable porous CuFeSe2/Au heterostructured nanosphere has been successfully fabricated via a simple photoreduction method and used for specific and sensitive detection of gaseous Raman weak-intensity aldehydes and lung cancer cells simultaneously. Benefiting from the numerous holes on the surface of the nanostructure stacked by a lot of nanoparticles, the CuFeSe2/Au nanospheres overcome the long-term limitations of the gaseous molecules that are hard to absorb on solid substrates. Therefore, when the Raman-active molecule of 4-ATP was pregrafed on the CuFeSe2/Au nanospheres, the sensitivity of the gaseous aldehydes can be greatly improved with limits of detection as low as the 1.0 ppb level. Meanwhile, such CuFeSe2/Au nanospheres present a high SERS activity to RBITC, which makes the nanostructures detect A549 cells with high sensitivity and selectivity. In addition, such heterostructured nanosphere has excellent photocatalytic cleaning performance and could provide efficient renewable properties. We believe that this new type of renewable porous CuFeSe2/Au nanospheres will find more potential applications in sensing, biomedical, and bioanalytical assays.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.8b06116. Experimental details, TEM image and size-distribution histograms, HRTEM image of CuFeSe2 NCs, EDX of CuFeSe2 NCs, XPS spectra of CuFeSe2 NCs, XPS F


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spectra of CuFeSe2 frameworks, XPS spectra of DIBTETA and CuFeSe2 frameworks about O1s, FT-IR spectra of CuFeSe2 frameworks, CuFeSe2 NCs, and DIB-TETA, EDX of CuFeSe2/Au nanospheres, UV− vis−NIR spectrum of CuFeSe2/Au nanospheres, XPS spectra of CuFeSe2/Au nanospheres, XPS spectra of CuFeSe2 frameworks and CuFeSe2/Au nanospheres, FT-IR spectra of CuFeSe2/Au nanospheres and CuFeSe2 frameworks, SEM images of CuFeSe2/Au nanospheres shape evolution with increasing reaction time, SEM images of CuFeSe2/Au nanospheres shape evolution increasing concentration of HAuCl4·4H2O, normal Raman spectrum of CuFeSe2 NCs modified by 4-ATP or RBITC, Raman spectra of the benzaldehyde at different concentrations, SERS mapping of the Raman intensity of CN peaks at 1616 cm−1, normal Raman spectrum of CuFeSe2/Au nanospheres modified by 4ATP or RBITC with an excitation source of 532 or 633 nm, normal Raman spectrum of solid RBITC, Raman spectra of the R6G under illumination and without illumination, UV−vis spectra of FA-CuFeSe2/Au nanospheres, cell viability of A549 and NIH3T3 cells incubated with FA-CuFeSe2/Au nanospheres with different concentrations, analysis of A549 and NIH3T3 cells incubated with RBITC-labeled FA-conjugated CuFeSe2/Au nanospheres using a confocal Raman microscope with a 785 nm laser excitation, SEM image of CuFeSe2/Au nanospheres after detecting cancer cells, composition of nanoparticles calculated from inductively coupled plasma atomic emission spectrometry, Raman data of substrate molecules, target detection based on the HPLC method, and additional references (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Fengjuan Chen: 0000-0002-1663-4812 Baodui Wang: 0000-0003-1600-6557 Author Contributions †

H.W. and H.W.: These authors contributed equally to this work. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (21671088, 21431002, and 21876072) and the Fundamental Research Funds for the Central Universities (lzujbky-2018-it03). We wish to thank the Electron Microscopy Centre of Lanzhou University for the microscopy and microanalysis of our specimens.

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