A Au nanoflower@SiO₂@CdTe/CdS/ZnS quantum dot multi-functional nanoprobe for photothermal treatment and cellular imaging

Abstract

Au nanoparticle@SiO₂@CdTe/CdS/ZnS quantum dot (QD) composite structures were synthesized by a liquid phase synthesis method. In this paper, three steps were adopted to gradually grow PVP-stabilized Au seeds from which PVP-stabilized Au nanoflower (NF) structures were successfully synthesized. For the sake of controlling the distance between Au NFs and QDs, silica was used as the shell material for coating Au NFs. The applications of this multi-functional nanoprobe in photothermal treatment and bio-labeling were demonstrated on MCF-7 and MDA-MB-231 breast cancer cells labeled with Au NF@SiO₂@QDs. The experimental results of viability staining indicate that Au NF@SiO₂@QDs composites with an excitation threshold of the photothermal effect of only 1.0 W cm⁻² exhibit excellent photothermal conversion efficiency owing to the large absorption cross sections of Au NFs. Compared with that of pure QDs, the fluorescence efficiency of Au NF@SiO₂@QDs was increased by 40%, which could be attributed to localized surface plasmon enhanced dipole radiation. Fluorescence imaging results reveal that Au NF@SiO₂@QDs targeted the membrane of cancer cells showing strong fluorescence. Therefore, it can be concluded that the composite structure combines the therapeutic and diagnostic modalities.

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1 Introduction

Metal nanoparticles have promising applications in photothermal therapy,¹ surface plasmon enhanced Raman scattering (SERS),² and surface plasmon enhanced fluorescence³ because of their localized surface plasmon resonance (LSPR) properties. Electromagnetic waves interact with the surface conduction electrons of metal nanoparticles, producing a collectively coherent resonance, namely a LSPR phenomenon.⁴ Upon being confined to the metal nanoparticle, the localized surface plasmons can result in strong absorption, scattering and significant electric field enhancement around metal nanoparticles.^5,6

Owing to tunable light absorption/scattering properties, metal nanostructures have recently been demonstrated as a photothermal agent for cancer therapy. Photothermal therapy is the application of strong absorption phenomena, typically involving the conversion of light energy to localized heat, which is used to deconstruct the cancer cells.¹ In the therapy process, incident light can penetrate to a depth of several centimeters through tissue in the near-infrared region (650–950 nm),^7,8 where water and hemoglobin have weak absorption. Hence, an 808 nm laser is widely used to research photothermal efficiency for in vivo applications. When the LSPR peak of a metal nanoparticle matches the incident light, the photothermal conversion efficiency of the nanoparticle can be improved efficiently. Based on this, Au nanoparticles with near-infrared (NIR) absorption were investigated for use as a photothermal agent.⁷ The central peak of LSPR can be tuned from the visible to near-infrared regions by changing the size, shape and morphology of the Au nanoparticles.⁹ Wyatt and co-workers suggest that the cytotoxicity of gold is negligible.¹⁰ Coupling this with the fact that gold is known to be resistant to oxidation and is biologically inert,¹¹ it is justified that Au nanoparticles are ideal materials for photothermal therapy. Up to now, many groups have made efforts to explore synthetic routes of different gold nanostructures, including nanosphere,¹² nanorod,¹³ nanoprism,¹⁴ nanocage¹⁵ and nanostar.^16,17 The key of photothermal therapy is to improve absorption intensity and photothermal transduction efficiency. Branched Au nanoparticles with a large absorption cross section at the position of the LSPR peak are novel photothermal nanostructures.^18,19 In addition, this type of nanoparticles can produce a strongly localized and enhanced electric field in the sharp and spiky region.

Recently, metal composite structures have attracted great attention. The combination of therapeutic and diagnostic components into a nanostructure can be used to monitor biological processes and achieve treatment at the same time. Such composite nanostructures allow for the imaging and detection of the targeted position, which improve the specificity and increase the efficacy of treatment.² Vo-Dinh et al.² synthesized a Au nanostar and a protoporphyrin IX composite structure combining Raman imaging and the photothermal effect. Quan Li et al.²⁰ confined the photosensitizer (PS) methylene blue (MB) in the vicinity of a Au nanorod, researching the role of the plasmonic effect in enhancing drug efficacy. Khlebtsov et al.²¹ reported a Au–Ag nanocage and Yb-2,4-dimethoxyhematoporphyrin nanocomposites. In previous studies, dyes have been used as fluorescence materials in photothermal and fluorescent composites, which is not beneficial for in vivo applications. Compared with traditional dyes, quantum dots (QDs) have unique properties. A narrow and size-dependent emission spectrum, anti-photobleaching, and high brightness make QDs attractive for bio-labeling. Considering the low toxicity and the high fluorescent effect of QDs, CdTe/CdS/ZnS core–shell QDs were adopted.²²

In this paper, Au NF@SiO₂@QDs structures were synthesized. An Au nanoparticle core–shell composite structure combines therapeutic and diagnostic components in a nanostructure,² which have potential applications in the medical field. Silica is a widely used material for synthesizing concentric core–shell nanostructures.²³ Au NF coated by a silica shell is efficient for enhancing stability and improving biocompatibility. In the process of the experiment, the SPR peak of Au NFs was tuned to the NIR region to match the wavelength (808 nm) of the laser by changing the amount of seeds. Under resonance excitation, Au NF@SiO₂@QDs composites linking with antibody (AT) reveal high photothermal transduction efficiency. In addition, it was confirmed that Au NF@SiO₂@QDs–AT composites can target the membrane of MCF-7 and MDA-MB-231 breast cancer cells, serving as a fluorescent probe for labeling of cells. Therefore, Au NF@SiO₂@QDs nanoparticles will have great prospect in photothermal treatment and bio-labeling.

2 Experimental

2.1 Materials

Chloroauric acid (HAuCl₄, AR), sodium borohydride (NaBH₄, ≥96.0%), cetyltrimethylammonium bromide (CTAB, ≥99.0%), ascorbic acid (AA, ≥99.7%), poly (vinylpyrrolidone) (PVP, powder, M_w = 10 000), deionized water (18.25 MΩ cm), N,N-dimethylformamide (DMF, 99.8%), tetraethyl orthosilicate (TEOS) (28.4% SiO₂, AR), ethanol (99.7%), ammonia (25–28% NH₃, AR), 3-aminopropyltrimethoxysilane (APS, Sigma) (98%), zinc chloride (ZnCl₂, 99%), cadmium chloride (CdCl₂·2.5H₂O, 99%), thioacetamide (TAA, 99%), tellurium powder (99.999%), 2-propanol, 3-mercaptopropionic acid (MPA), sodium hydroxide (NaOH, ≥96.0%), rabbit anti-CK19 (Beijing Biosynthesis Biotechnology Co., Ltd.), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS) and 4′,6-diamidino-2-phenylindole (DAPI), were used without further purification. Cell culture media, supplements, MCF-7 and MDA-MB-231 breast cancer cells were all supplied by First Affiliated Hospital of Anhui Medical University.

2.2 Synthesis of a Au nanosphere

First, synthetic methods for about 3 nm Au nanospheres were similar to the one reported previously.²⁴ 0.6 mL of ice-cold NaBH₄ (10 mM) was added to a mixture of 10 mL of HAuCl₄ (0.25 mM) and CTAB (0.1 M). The solution was incubated for least 3 h at 30 °C. Second, 12 mL of a water solution containing HAuCl₄ (0.25 mM) and CTAB (0.1 M), and 5 mL of AA (0.09 M) were mixed together. 0.3 mL of the as-prepared suspension of Au nanospheres was added to the solution mixture to form larger nanospheres. After 1 min, this colorless solution turned red. The product was spinned down at 12 000 rpm for 45 min. Last, the product was dispersed in 1 mL pure water for further application.

2.3 Synthesis of a PVP-stablized Au seed

200 μL of the as-prepared Au nanosphere solution was added to 6 mL of DMF solution containing HAuCl₄ (0.16 mM) and PVP (M_w = 10 000) (0.21 M). Then, the reaction solution was heated in oil bath at 80 °C for 1 h with stirring. The product was used as seeds for the preparation of nanoflowers.

2.4 Synthesis of a Au nanoflower

15 mL of a DMF solution containing PVP (9 M) and 180 μL of HAuCl₄ were mixed.²⁵ Au seeds were then added under continuous stirring and allowed to react for 2 h. The product was rinsed two times and then dispersed in 20 mL of ethanol for further application.

2.5 Preparation of Au nanoflower@SiO₂

The SiO₂ shell was grown on the surface of a Au nanoflower by the Stöber method. The detailed synthesis process was described as follows: 3 mL of water was added to the as-prepared Au nanoflower ethanol solution. Then, 1 mL of the ammonia aqueous solution was introduced. Under vigorous stirring, 15 μL, 20 μL and 80 μL of mixture of APS and TEOS (the molar ratio was 2 : 1) was injected. The solution was washed with ethanol and dissolved in pure water for further application after 20 min.

2.6 Preparation of CdTe/CdS/ZnS QDs

NaHTe was prepared by adding 50 mg NaBH₄ and 80 mg Te to 2 mL water. CdCl₂·2.5H₂O and MPA were added to 100 mL pure water. Then, the solution was adjusted to pH 8.5 by adding 0.5 M NaOH. After being deaerated with N₂ for 1 h, the NaHTe solution was added (Cd : Te : MPA = 2 : 1 : 4.8). The solution mixture removed oxygen for 5 h at 100 °C. The as-prepared CdTe QDs were washed with 2-propanol and dispersed in 5 mL of deionized water. 0.1 mmol CdCl₂·2.5H₂O and 0.3 mmol MPA were added to 95 mL of water. Then solution was adjusted to pH 8.5 with 0.5 M NaOH. After adding 0.1 mmol TAA and the CdTe QD solution, the solution mixture was refluxed for 1 h at 100 °C. The as-prepared CdTe/CdS QDs were washed with 2-propanol and dispersed in 5 mL of deionized water. 0.1 mmol ZnCl₂ and 0.3 mmol MPA were added to 95 mL. The mixture was adjusted to pH 8.5 with 0.5 M NaOH. Then, 0.1 mmol TAA and CdTe/CdS QDs were added. The mixture was refluxed for 1 h at 80 °C.^26,27

2.7 Preparation of Au NF@SiO₂@QDs and covalent conjugation Au NF@SiO₂@QDs with antibody

100 μL of QDs was added to the Au NF@SiO₂ water solution. After 10 min ultrasound, the product was centrifuged and dissolved in PBS solution. 50 μL EDC (20 mg mL⁻¹) and 5 μL NHS (20 mg mL⁻¹) were added into PBS solutions of Au NF@SiO₂@QDs. All of the samples were incubated at 37 °C for 1 h in a table concentrator. 100 μL (0.1 mg mL⁻¹) of antibody was added to the PBS solution. Then, the mixture was incubated at 37 °C for 1 h. The product was finally washed with the PBS solution for further application.

2.8 Photothermal effect of Au NF@SiO₂@QDs–AT

MCF-7 breast cancer cells were seeded on 6-well culture plates in DMEM medium and maintained overnight at 37 °C in a humidified 5% CO₂ atmosphere. 100 μL Au NF@SiO₂@QDs–AT and the same amount of the PBS solution were added into the medium. The cells were cultured for 3 h. Then, the cells were washed with PBS and irradiated by an 808 nm laser at a power density of 1.0 W cm⁻². Prior to viability staining, cells were cultured for 5 h at 37 °C in a humidified 5% CO₂ atmosphere. The viability state of cells was investigated using a dark-field microscope.

2.9 Fluorescence labeling effect of Au NF@SiO₂@QDs

MCF-7 and MDA-MB-231 breast cancer cells were cultured on coverslips in DMEM medium containing 10% fetal bovine serum. The coverslips were carefully washed three times with the PBS solution. Then, Au NF@SiO₂@QDs–AT composite structures were added onto these coverslips and incubated for 1 h at 37 °C. Prior to imaging, the coverslips were washed three times with PBS. Cell images were observed using a fluorescence microscope.

2.10 Characterization

The morphological information of nanoparticles was obtained by transmission electronic microscopy (TEM, JEOL, JEM-2010) and scanning electron microscopy (SEM, JSM-6700F). The UV-visible absorbance spectra were measured by using a UV-3600 UV-VIS-NI spectrophotometer. Photoluminescence spectra were obtained using an F-4600 fluorescence spectrophotometer. Cells were imaged using an Olympus IX 73 fluorescence microscope and a Leica SP5 laser scanning confocal microscope.

3 Results and discussion

The procedure for the production of composite structures is shown schematically in Fig. 1. The reduction method of NaBH₄ was used to produce small Au seeds. Then, the larger Au nanospheres were synthesized with the reduction of AA. As is well known, the growth processes of nanoparticles comply with the rules of kinetics and thermodynamics: small Au nanospheres and larger Au nanospheres were all synthesized at ambient temperature. The thermal stability is not strong. After storing for a few days, the nanoparticles will grow further. It is not beneficial for us to tune the SPR peak of nanoflowers by controlling the amount of seeds. Therefore, we introduced a synthesis process of PVP-stabilized Au nanoparticles using a weak reducing agent in a heating environment. The product has good stability at room temperature, which was appropriate for seeds of Au NFs. After producing a batch of seeds, a few nanoflower samples can be synthesized to form a small database by adding different amounts of seeds. The SPR peak of nanoflowers can be easily tuned to the target wavelength position according to this database. Carboxyl group terminated QDs were assembled to the surface of Au NF@SiO₂. Finally, antibodies were further coupled with the surface of Au NF@SiO₂@QDs in the presence of EDC and NHS as activating reagents. Au NF@SiO₂@QDs composites exhibited photothermal and fluorescent effects, which have potential applications in photothermal treatment and cellular imaging.

Fig. 1 Schematic illustrating the synthesis of Au nanoflower@SiO₂@QDs composite structures.

Gold nanoflowers were prepared by the method of seed growth. PVP-stablized Au nanoparticles were adopted as seeds, which are shown in Fig. 2A. Au nanoflower samples of five different sizes were prepared by adding different amounts of seeds. Fig. 2B–F show TEM images of nanoflowers with different sizes. These nanoflowers have a relatively uniform size and shape distribution. The average sizes of five samples were measured to be 40 nm, 80 nm, 120 nm, 130 nm and 150 nm, respectively. The volume of seeds is gradually reduced from 2000 μL, 1300 μL, 650 μL, 520 μL to 260 μL.

Fig. 2 TEM images of (A) Au seeds, and Au nanoflowers made from different volumes of seeds: (B) 2000 μL, (C) 1300 μL, (D) 650 μL, (E) 520 μL and (F) 260 μL.

Fig. 3A shows the absorption spectra of five samples and seeds. The absorption peak of nanoflowers can be tuned from the visible light region to the near-infrared region. The plasmon resonance wavelength of seeds is 527 nm. With the reduction of seed amount, the plasmon resonance wavelengths of five Au nanoflowers samples are varied from 581 nm, 659 nm, 792 nm, 829 nm to 890 nm. The SPR peak is closely related to local electric field distribution of metal nanoparticles. The amplitude of the local field influences the energy of SPR, which corresponds to the SPR wavelength. The charges are located at the sharp corners of each nanoparticle. The distance between positive and negative charges equivalent to the charge center increases with the increasing nanoparticle size, which causes the increase of the plasmons restoring force and the shift of the SPR peak.²⁸ In order to research the influence of PVP concentration on the absorption peak of the product, three samples were synthesized by changing the concentration of PVP only. Fig. 3B shows the absorption spectra of the three samples. The absorption peaks of the product exhibit a blue shift with reducing PVP concentration. With further decrease of PVP concentration, the absorption peak approaches the peak of the seed. The mechanism should be that high ratios of vinylpyrrolidone monomeric units to Au atoms lead to a rapid, kinetically controlled and preferential growth along certain crystalline facets.²⁹ Nanoparticles will grow along the crystalline facets with low surface free energies based on thermodynamic control. With the decrease of PVP concentration, the preferential growth processes of nanoparticles were restrained, which inhibit the formation of the branched nanostructure and enable the formation of a nanostructure that is similar to spherical nanoparticles.

Fig. 3 (A) Normalized absorption spectra of Au seeds and Au nanoflowers. From left to right is the absorption of samples corresponding to A–F in Fig. 2. (B) Extinction spectra of Au nanoflower samples grown in the solution with different concentrations of PVP.

To further demonstrate the core–shell structure of Au NF@SiO₂ and Au NF@SiO₂@QDs, the morphologies of these nanoparticles were obtained by TEM. Fig. 4A and B show the TEM image and the schematic plot of the Au NF@SiO₂ (the silica shell thickness is about 9 nm) composite structure, respectively. Fig. 4C and E show the silica shell thickness of Au NF@SiO₂ to be about 16 and 65 nm, respectively. Corresponding Au NF@SiO₂@QDs composite nanoparticles are shown in Fig. 4D and F. It can be observed that these nanoparticles are homogeneous core–shell structures. The thickness of the silica shell increased with increasing TEOS. Surface-protective agents play a significant role in preventing aggregation and surface-modifying function for further application. Herein, aminopropyltrimethoxysilane (APTMS) was chosen to modify the surface of SiO₂, which can provide an amino group for combining negatively charged QDs.

Fig. 4 (A) TEM image and (B) schematic plot of Au nanoflowers@SiO₂, respectively. (C and E) TEM images of the obtained Au nanoflowers@SiO₂ with different shell thickness. (D and F) TEM images of Au nanoflowers@SiO₂@QDs corresponding to different thickness of the silica shell.

The silica shell was used to control the distance between the Au nanoflower and QDs, which prevents fluorescence quenching phenomena of QDs caused by charge transfer. In general, PL quenching occurs when the distance between metal nanoparticles and fluorophores is less than 5 nm. PL enhancement is achieved at larger distances (7–20 nm).^30,31 So, Au NF@SiO₂@QDs nanoparticles with a silica shell of 16 nm were used in the subsequent experiment. The SPR peak of Au NF@SiO₂@QDs has 36 nm redshift compared with that of Au NF due to the change in the dielectric environment (Fig. 5A). The SPR peak of Au NF was tuned from 779 nm to 815 nm, which matches with the 808 nm laser. The amount of red-shifting is related to the thickness of the silica shell. In order to match the absorption peak of Au NF@SiO₂@QDs with the wavelength of the laser, the SPR peak of Au NFs and the amount of TEOS added should be considered at the same time. Fig. 5B shows the fluorescence spectra of QDs before and after connecting to Au NF@SiO₂ by self-assembly, with the excitation of 365 nm light. It was clear that Au NF@SiO₂@QDs has efficient PL enhancement (up to an enhancement factor of 1.4) compared with pure QDs. Generally, PL enhancement contributes to two mechanisms. One is excitation enhancement caused by the efficient enhancement of the local field associated with the resonance coupling between the LSP of metal and incident electromagnetic field, which can induce the efficient increase of absorption and the excitation rate. The other is the increase of the radiative decay rate caused by the resonance coupling between the LSP of metal nanoparticles and fluorophore emission.³¹ The LSPR bands of Au NFs have a large degree of spectral overlap with the emission wavelength of QDs (615 nm). Therefore, PL enhancement should be caused by the second mechanism.

Fig. 5 (A) Extinction spectra of Au NFs (red line) and Au NF@SiO₂@QDs (black line). (B) Fluorescence spectra of QDs (black line) and Au NF@SiO₂@QDs (red line). (C) Absorption cross section of the Au NF model, (inset) the simplified model. Simulated electric field intensity distribution (D) in the yz plane at x = 0, (E) in the xz plane at y = 0, (F) in the xy plane at z = 0. The incidence direction is along the x axis. The polarization of the incident light is along the y axis.

With the aim of explaining the excellent photothermal effect of Au NFs, the electric field distribution is calculated using a three-dimensional finite-difference time-domain method (FDTD). The boundary conditions of the computational domain were set to perfectly matched layer absorbing boundaries. The simulation region is 1 μm × 1 μm × 1 μm, and the cell size is 1 nm × 1 nm × 1 nm. A linearly polarized plane wave with 780 nm wavelength irradiates Au NF along the x axis. Au NF was simulated by employing a geometrical model consisting of a central sphere with 18 tapered cylinders, which possess a round tip (see inset in Fig. 5C). The tip radius and cone angle were set to 3.5 nm and 25°, respectively. All the parameters chosen here are consistent with the average value obtained in the experiment (see Fig. 4C). As seen in Fig. 5C, the absorption cross section spectrum of the simplified model matches the experimental result. There are two characteristic LSPR peaks: a very intense peak around 780 nm and a weaker peak around 550 nm. The corresponding E-field distribution calculated with the FDTD method is shown in Fig. 5D–F. The largest local electric field is accumulated on the tips of Au NFs, thereby producing a large field enhancement. In addition, there is a large absorption cross section, making Au NFs ideal for photothermal therapy.

The temperature–time curve was measured in order to research the photothermal conversion efficiencies of Au NF@SiO₂@QDs composites. As shown in Fig. 6, the temperature of Au composite solution (0.102 mmol L⁻¹) increased rapidly in the first five minutes and gradually reached a plateau at 46.2 °C with the irradiation of an 808 nm laser at a power density of 1.0 W cm⁻². As a control group, the temperature of the PBS solution increased at a slower rate under similar conditions. Ultimately, the temperature of the control group remained stable at around 33.5 °C.

Fig. 6 Temperature plot as a function of irradiation time.

The viability staining of MCF-7 breast cancer cells was used to verify the photothermal effect of Au NF@SiO₂@QDs. The experiment group was incubated with Au NF@SiO₂@QDs–AT (Fig. 7C). The control group one was incubated with the same volume of the PBS solution (Fig. 7A). The control group two was incubated with Au NF@SiO₂@QDs–AT (Fig. 7B). The experiment group and the control group one were irradiated by an 808 nm laser at a power density of 1.0 W cm⁻². The control group two was kept in the same environment with the experiment group but without laser irradiation. After culturing for 5 h, cells were studied by viability staining. A fluorescence terminating agent (containing metanil yellow and ethidium bromide) was added to the three groups. Metanil yellow can react with the cell membrane, and the membrane of live cells can be dyed green. Ethidium bromide can penetrate the cell membrane that was damaged to make the cell nucleus turn orange-red. Therefore, orange-red stained cells are dead cells, and green-stained cells are live cells. As shown in Fig. 7, the photothermal effect of Au NF@SiO₂@QDs is obvious. The experiment group exhibits cell detachment due to the heating effect. The temperature of this group is up to the cytotoxic level, which is 43–48 °C. Protein denaturation takes place.³² The control group one and two hardly showed any cell death phenomena. The only difference between the control group one and experiment group is the absence of Au NF@SiO₂@QDs–AT. The two groups have the same conditions of irradiation. The viability result of the two groups suggests that the laser intensity is hardly harmless to cells without Au NRs in the experiment. The viability of cells in the control group two did not drop, which testifies that the introduction of Au NF@SiO₂@QDs–AT is not the direct reason of the death of cells in the experiment group. Therefore, these results show that the photothermal effect of Au NF@SiO₂@QDs terminates cells.

Fig. 7 Viability staining of MCF-7 breast cancer cells incubated with (A) PBS solution and with laser irradiation, (B) Au NF@SiO₂@QDs–AT and without irradiation, and (C) Au NF@SiO₂@QDs–AT and with laser irradiation.

Next, Au NF@SiO₂@QDs nanoparticles were applied for cellular imaging. The images of the cell were collected after being stained with the composite structure. Fig. 8A and B show the bright-field image and fluorescence image of the MCF-7 breast cancer cells, respectively. The bright-field image and fluorescence image of MDA-MB-231 breast cancer cells are shown in Fig. 8C and D. Fluorescence images of MDA-MB-231 breast cancer cells clearly indicate that ultraviolet irradiated cells emit strong red fluorescence. Subsequently, they were stained with DAPI to visualize the nuclei. The bright-field image and fluorescence image of MDA-MB-231 breast cancer cells with the treatment of Au NF@SiO₂@QDs–AT and DAPI are shown in Fig. 8E and F, respectively. In order to observe the structure of MDA-MB-231 breast cancer cells more clearly, a laser scanning confocal microscope was used. The fluorescence confocal images are shown in Fig. 9A–C, which showed three situations of the two channel output. The red channel corresponds to QDs, and the blue channel is DAPI. The images were obtained under 365 nm UV excitation. As is shown in Fig. 9B, the nuclei were stained blue. Fig. 9C shows that MDA-MB-231 breast cancer cells definitely emit red fluorescence, indicating that Au NF@SiO₂@QDs successfully targeted the membrane of the cells.

Fig. 8 Bright-field image of (A) MCF-7 breast cancer cells with the treatment of Au NF@SiO₂@QDs–AT, (C) and (E) MDA-MB-231 breast cancer cells with the treatment of Au NF@SiO₂@QDs–AT and Au NF@SiO₂@QDs–AT/DAPI, respectively. (B), (D) and (F) fluorescence image corresponding to (A), (C) and (E), respectively.

Fig. 9 Image of MDA-MB-231 breast cancer cells taken under the conditions of (A) red and blue, (B) blue, (C) red channel output.

4 Conclusions

PVP-stabilized Au NFs with a tunable SPR peak were synthesized. Silica was deposited onto the surface of Au NFs through the optimized Stöber method, acting as the medium for Au NFs and quantum dots. Numerical simulation shows that Au NFs with an enhanced local electric field and a large absorption cross section are suitable for photothermal therapy. The photothermal and fluorescent properties of the Au NF@SiO₂@QDs nanoprobe were demonstrated on MCF-7 and MDA-MB-231 breast cancer cells. Photothermal test shows that the nanoprobes can successfully convert NIR irradiation to thermal energy, which causes the death of cancer cells. Fluorescence images intuitively indicate that nanoprobes can target the membrane of breast cancer cells and emit strong fluorescence. Combined together, it can be concluded that Au NF@SiO₂@QDs multi-functional nanoprobes have significant applications in photothermal treatment and cellular imaging.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (no. 51272246 and no. 81172082), and the Fundamental Research Funds for the Central Universities of China (Grant no. 2030000001).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra02965h

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