Confining the polymerization of aniline to generate yolk–shell polyaniline@SiO₂ nanostructures

Abstract

The polymerization of aniline was realized in a confined space by using CeO₂ nanoparticles as reactive templates that were encapsulated by SiO₂. The weak solubility of CeO₂ in acidic solution, resulting in the slow release of Ce⁴⁺ ions with a high oxidizing potential, and the porous structure of the SiO₂ shell allowed an equilibrium to be established between the diffusion of aniline inward and Ce⁴⁺ ions outward from the shell, and the polymerization of aniline in the cavity. The influence of the shell thickness, reaction temperature and aniline concentration on the generation of the yolk–shell nanostructures was investigated in detail. By virtue of the excellent photothermal property of polyaniline that was confined in the SiO₂ shell, the product was applied in drug loading and photothermal release using 5-fluorouracil as a representative anticancer drug.

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1. Introduction

Polyaniline (PANI), as one of the most important conducting polymers, has received significant interest in recent years and it has been widely applied in various fields, including devices, sensors and energy storage.^1–5 To improve the properties of PANI, a commonly adapted strategy is to construct PANI nanostructures, such as nanospheres, nanofibers, nanotubes and hierarchical structures because of their so-achieved high specific surface area and large number of active sites.^6–9 However, one obstacle is to avoid their tendency to aggregate due to their high activity. The introduction of electro-repulsion and steric stabilizers into these systems can greatly relieve this pressure.^10,11 On the other hand, confining PANI nanostructures into a local space should be another effective way. In this case, a porous shell and a void are important for PANI to take its roles. For this purpose, SiO₂ is a preferential choice to separate every single PANI nanoparticle (NP) from direct contact. Although the polymerization of aniline on SiO₂ surface has been readily accomplished to achieve SiO₂@PANI,¹² encapsulation of SiO₂ on PANI has been rarely reported,¹³ possibly due to the non-compatible interface for the deposition of SiO₂. Furthermore, the full coating of SiO₂ on PANI limited the application of the cores because the loading target materials do not have effective space to interact with PANI.

Of all the methods for synthesizing PANI nanomaterials, a scarified template method should be pointed out, where a material with a relatively high oxidizing ability is used as both template and oxidant and the following interfacial polymerization of aniline on the surface of the template leads to the disappearance of the template and generation of PANI with a unique nanostructure, typically keeping the original morphology of the template. MnO₂ is one of the most adaptable materials for this purpose and PANI nanotubes and hollow nanocubes have been synthesized based on the reactivity of MnO₂.^14,15 Similarly, other kinds of oxides with a reasonable valence state can also be utilized as oxidants for the polymerization of aniline.¹⁶

In this report, we selected CeO₂ as a reactive template that was encapsulated by a layer of SiO₂ for the polymerization of aniline. CeO₂ has weak solubility in acidic aqueous solution and the slowly released Ce⁴⁺ ions with a high oxidizing potential allowed the confined polymerization of aniline that penetrated through the SiO₂ layer. As a proof of concept, the produced yolk–shell nanostructured PANI@SiO₂ was utilized for drug loading and photothermal release owing to the promising photothermal property of PANI^17–19 and the isolated effect assisted by the porous SiO₂ shell.

2. Experimental

2.1 Materials

Ce(NO₃)₃·6H₂O (99%, Aldrich), CH₃COOH, ethylene glycol (EG), ethyl silicate (TEOS), ammonia solution (Beijing Chemical), polyvinylpyrrolidone (PVP, K30, Sinopharm) and PVP (K15, TCI) were used as received. Aniline (98%, TCI) was distilled before use and stored at 4 °C. All solutions were prepared using ultrapure water (resistivity > 18 MΩ cm⁻¹).

2.2 Characterization

The morphologies of the samples were examined using a high resolution transmission electron microscope (HRTEM, JEOL-2100F) operated at 200 kV and a scanning electron microscope (SEM, JEOL SM-6360LV). The X-ray powder diffraction (XRD) patterns of the resultant samples were obtained on a Siemens D5005 Diffractometer with Cu Kα radiation. The UV-vis spectra of the products were measured with a UV-vis spectrometer (UV-2550). The Fourier transform infrared (FT-IR) spectrum was obtained with a Bruker IFS 66 V instrument.

2.3 Synthesis of CeO₂ NPs

The CeO₂ NPs were synthesized using the typical method²⁰ with a slight modification. Ce(NO₃)₃·6H₂O (2.0 g) was dissolved in a mixture of CH₃COOH/H₂O (4 mL, v : v = 1 : 1) with EG (60 mL) added later, and then stirred for 30 min to form a homogeneous solution. Subsequently, it was transferred into a 100 mL Teflon-lined stainless-steel autoclave and kept at 180 °C for 150 min. After the reaction was complete, the autoclave was cooled down to room temperature naturally and the precipitates were collected by centrifuging and washing several times with water and ethanol. Finally, the pale yellow products were dried at 65 °C in air for 5 h for further characterization and application.

2.4 Synthesis of CeO₂@SiO₂ NPs

CeO₂@SiO₂ core–shell NPs were prepared through a modified Stöber method. Typically, the above synthesized CeO₂ NPs (220 mg) were dispersed in ethanol (4 mL) and mixed with PVP aqueous solution (1 M, 2 mL) with the help of ultrasonication for 10 min to make sure the surfaces of CeO₂ were well modified. Afterwards, the above solution was hybridized with a mixture of ethanol (2.88 mL), water (4.4 mL) and aqueous ammonia (1.6 mL), followed by the addition of TEOS (0.4 mL) in ethanol (8 mL) under vigorous stirring for 3 h at room temperature to grow the silica shell. Finally, the resultant samples were collected using centrifugation and cleaned with water and ethanol several times, then dried in an oven at 65 °C for 5 h.

2.5 Synthesis of PANI@SiO₂ NPs

Briefly, CeO₂@SiO₂ (220 mg) was dispersed in water (18 mL) with an aniline aqueous solution (0.05 M, 120 mL) added subsequently under stirring for 1 h to allow adequate aniline to adsorb onto the particle surface. Then HCl (0.1 M, 60 mL) was added into the solution with continuous stirring for another 48 h. During the process, the color of the reaction system slowly changed from white to blue to dark green, indicating the polymerization of aniline. Finally, the resultant samples were obtained using centrifugation, washed with water and ethanol several times and dried in an oven at 65 °C for 12 h. The SiO₂ shell was disposed with “surface-protected etching” by PVP to form a mesoporous structure. The procedure was as follows: PVP (K15, 500 mg) was ultrasonically dissolved in a PANI@SiO₂ solution (40 mL) and refluxed at 100 °C for 4 h, then it was cooled down to room temperature naturally. NaOH solution (0.01 g mL⁻¹, 2 mL) was injected into the solution to induce etching. Later, the obtained products were washed with water several times and dried at 65 °C for further use.

2.6 In vitro 5-fluorouracil (5-FU) loading into PANI@SiO₂ NPs

In a typical procedure, 5-FU loaded PANI@SiO₂ NPs were prepared by mixing a 5-FU ethanol solution (3 mg mL⁻¹, 1 mL) with PANI@SiO₂ NPs (2 mg) for two days at room temperature. Meanwhile, the supernatant was obtained by centrifuging the as-obtained products at 8000 rpm for 5 min. To evaluate the amount of 5-FU loaded into the PANI@SiO₂ yolk–shell NPs, the concentration of the initial 5-FU and the supernatant were determined using UV-vis absorption spectroscopy at 265 nm. The 5-FU loading efficiency (LE) can be calculated using the following equation:

LE% = [(Abs_{(original 5-FU)} − Abs_{(residual 5-FU)})/Abs_{(original 5-FU)}] × 100%.

2.7 In vitro release of 5-FU from 5-FU-loaded PANI@SiO₂ NPs

The release experiment was performed by dispersing two equal portions of the as-synthesized products into 1 mL of phosphate buffer saline (PBS). One was carried out at room temperature, the other was exposed to an excitation laser of 808 nm at fixed times. The supernatant was taken out by centrifuging to test the concentration of released 5-FU by UV-vis measurement at 265 nm and replaced with fresh PBS solution at selected time intervals.

3. Results and discussion

3.1 Formation of yolk–shell PANI@SiO₂ nanostructures

In order to confine the polymerization of aniline, either the aniline monomer or the oxidant needs to be localized in an isolated space. In our strategy, we select CeO₂ with a higher valence state as the oxidant source and a layer of SiO₂ is encapsulated on its surface, as shown in Scheme 1. After the sequential addition of aniline and HCl aqueous solution, PANI is formed in the cavity and a yolk–shell structure is constructed. The advantage of selecting CeO₂ is based on the following four reasons: (1) the synthesis process is easy; (2) the morphology is controllable; (3) the encapsulation is easy to be realized with few disturbances; (4) the solubility of CeO₂ in acidic solution is weak. The SiO₂ layer plays two important roles: (1) it allows the diffusion of HCl and aniline into the inner part; (2) it provides an isolated space for the polymerization of aniline by Ce⁴⁺ that is generated from the reaction between CeO₂ and HCl.

Scheme 1 Schematic representation of the synthetic process and application of the yolk–shell nanostructured PANI@SiO₂.

3.2 Morphology

The TEM image of the as-synthesized CeO₂ NPs is shown in Fig. 1A and the NPs have an average size of 130 ± 5 nm with a spherical shape. After the hydrolysis of TEOS, a layer of SiO₂ is deposited on the surface of CeO₂ (Fig. 1B), and the typical shell thickness is 10 ± 1 nm. HRTEM images (Fig. S1A–D†) display a lattice spacing of 0.31 nm, corresponding to the (111) facets of CeO₂. After reaction, PANI spheres are formed with an average size of 54 ± 5 nm (Fig. 1C), which is smaller than that of the original CeO₂ particles. The contraction of the core volume is perhaps related to the different diffusion/reaction rate (vide infra). No lattice fringes can be observed in the HRTEM image of the PANI@SiO₂ NPs, indicating the diminishing of CeO₂ and the formation of amorphous PANI (Fig. S1E†). The corresponding SEM image presents a smooth SiO₂ surface without any PANI particles attached on its surface (Fig. 1D).

Fig. 1 TEM images of CeO₂ (A), CeO₂@SiO₂ (B), and PANI@SiO₂ (C), and SEM image of PANI@SiO₂ (D).

3.3 Structure

To confirm the existence of PANI inside the SiO₂, XRD patterns of the CeO₂, CeO₂@SiO₂ and PANI@SiO₂ are provided in Fig. 2A. After polymerization, the original CeO₂ peaks located at 28.6°, 33.1°, 47.6° and 56.4° (JCPDS 65-5923) disappear, accompanied by the appearance of a broad band centred at 25°, indicating the exhaustion of CeO₂ and formation of amorphous PANI (Fig. 2A). The EDS spectrum of the products also confirms the absence of Ce after reaction in comparison with those of the original CeO₂ and CeO₂@SiO₂ NPs (Fig. 2D vs. S2A and B†). The typical bands at 400 and 800 nm in the UV-vis spectrum along with the disappearance of the 306 nm peak for CeO₂ (Fig. 2B) and the characteristic peaks at positions of 1050, 1292, 1495 and 1570 cm⁻¹ in the FTIR spectrum further verify the existence of PANI (Fig. 2C).^21,22

Fig. 2 XRD patterns (A) and UV-vis spectra (B) of CeO₂, CeO₂@SiO₂ and PANI@SiO₂ NPs; FT-IR spectrum (C) and EDS analysis (D) of yolk–shell PANI@SiO₂.

3.4 Establishment of diffusion–polymerization equilibrium

As for the formation of the yolk–shell nanostructure, we consider that a kinetic equilibrium is established between the diffusion and polymerization of aniline inward from the SiO₂ shell and the generation and diffusion of Ce⁴⁺ ions outward from the shell. In order to promote the confined polymerization of aniline in the cavity, the aniline monomers adsorb or diffuse onto/across the SiO₂ shell firstly. Upon addition of HCl aqueous solution, the CeO₂ cores slowly transform into Ce⁴⁺ ions with a relatively high oxidizing potential (1.61 V vs. RHE) that readily induce the polymerization of aniline in the presence of acid. Meanwhile, they have the tendency to escape from the cores and this definitely inhibits the polymerization process inside the shell. In order to achieve a reasonable diffusion–polymerization equilibrium, the influence of the main factors was investigated, including the shell thickness, the reaction temperature and the aniline concentration.

When the SiO₂ shell thickness is decreased from 10 nm to 3 nm, a yolk–shell structure is rarely achieved. We consider that the thinner shell facilitates the diffusion of Ce⁴⁺ ions outward from the cores and induces the polymerization of aniline near the SiO₂ surface that does not have enough time to cross the shell. The TEM image in Fig. 3A reveals the presence of a large amount of separately dispersed PANI nanofibers around a core. On the contrary, a thicker shell (30 nm) is also not acceptable for the generation of PANI in the cavity. In this case, the diffusion of the resulting Ce⁴⁺ ions outward from the shell is greatly inhibited. Meanwhile, the aniline monomers also encounter more obstruction to contact with the Ce⁴⁺ ions. The TEM results show that yolk–shell nanostructured PANI@SiO₂ particles are randomly generated due to the difficulty for both Ce⁴⁺ ions and aniline monomers (Fig. 3B).

Fig. 3 TEM images of the yolk–shell nanostructured PANI@SiO₂ obtained with thin (A) and thick (B) SiO₂ shell thickness; at 273 K (C) and 323 K (D); and with aniline concentrations of 60 mM (E) and 100 mM (F).

Another factor that influences the diffusion/reaction equilibrium is temperature. At a higher temperature, a faster diffusion speed for both Ce⁴⁺ and aniline is obtained, accompanied by a quicker polymerization rate of aniline. At the reaction temperature of 323 K, no PANI was found in the cavity and the PANI particles existed far from the original SiO₂ shell and were removed during the centrifugation process leaving hollow SiO₂ in the final sample (Fig. 3D). This also confirms the faster diffusion rate of Ce⁴⁺ than aniline. Furthermore, it appears that the dependence on temperature of the diffusion rate is much greater than that of the polymerization speed. In order to prove this assumption, the experiment was carried out at 273 K under otherwise the same conditions and the result shows nearly no PANI is formed (Fig. 3C). The lower temperature inhibits the diffusion rates of both the Ce⁴⁺ ions and aniline, and the latter rarely has occasion to transport through the SiO₂ layer to contact with the former, and therefore polymerization is hardly realized.

The weak solubility of CeO₂ in acidic solution is of great importance for the generation of the yolk–shell nanostructured PANI@SiO₂. In the absence of aniline, the morphology of CeO₂@SiO₂ was kept with nearly no change when HCl was added into the system. This can be also proved by the kinetic UV-vis spectra of CeO₂@SiO₂ in the acidic solution, where nearly no intensity decrease of the typical CeO₂ peak at 306 nm is observed (Fig. S3†). However, the small amount of Ce⁴⁺ originating from the weak dissolution of CeO₂ was quickly exhausted upon contact with the aniline, which induced the next generation of Ce⁴⁺ to further oxidize the aniline. In the corresponding kinetic UV-vis spectra, the original CeO₂ peak gradually disappears along with the peak intensity of the characteristic PANI bands increasing (Fig. S4†). Since the release rate of the Ce⁴⁺ ions is controlled by the addition of HCl, their induced polymerization of aniline is also rate-limited. As a result, once the CeO₂ core is dissolved completely, no further polymerization occurs. This can be revealed by the fact that the size of the PANI NPs increases along with the aniline concentration before [aniline] = 60 mM, but it does not further increase upon increasing the aniline concentration to 100 mM (Fig. 3E and F). Apart from that, pyrrole was chosen as a monomer to undergo such a confined polymerization process instead of aniline. Pyrrole has a lower oxidation potential than aniline (0.94 vs. 1.05 V, RHE), and hence it can be oxidized more easily. As a result, the original cavity was almost filled with polypyrrole (PPy) because of the faster polymerization rate at room temperature (Fig. S5†). When the reaction was carried out at a higher temperature (e.g. 323 K), PPy was found in all the inner part and even on the SiO₂ surface (Fig. S6†). Compared with the PANI system that generated hollow SiO₂ nanostructures, the faster polymerization rate of pyrrole led to a completely different morphology, possibly due to the reaction rate overwhelming the diffusion rate.

3.5 Application in drug loading and photothermal release

The strong absorption of PANI centered at 800 nm illustrates its possible application in photothermal release.²³ Besides, the confinement of PANI in the SiO₂ shell allows for the loading and delivery of drugs under specific conditions. For this purpose, yolk–shell nanostructured PANI@SiO₂ aqueous dispersions with concentrations ranging from 0 to 1 mg mL⁻¹ were irradiated using an 808 nm laser at a power density of 2.47 W cm⁻². In the absence of the sample, the water only increased by 4 °C from room temperature. Upon addition of the sample to form a concentration of 0.125 mg mL⁻¹, the temperature of the dispersion was raised by 12 °C after irradiation for 7 min. Increasing the concentration to 0.25, 0.5 and 1 mg mL⁻¹ led to the elevation of the temperature by 18.5, 27 and 29.5 °C, respectively (Fig. 4A). The thermal stability of the yolk–shell nanostructured PANI@SiO₂ was further studied. Upon laser irradiation for 6 min followed by naturally cooling to room temperature by switching off the laser, the time-dependent temperature of the PANI@SiO₂ dispersion was recorded for 6 cycles. The thermal conversion efficiency remains stable (Fig. 4B), indicating that the yolk–shell nanostructured PANI@SiO₂ fits well for application in drug photothermal release.²⁴

Fig. 4 (A) Temperature-change profiles of PANI@SiO₂ aqueous solutions at different concentrations under 808 nm laser irradiation (2.47 W cm⁻²); (B) temperature elevation cycles of PANI@SiO₂ NPs (1 mg mL⁻¹) under NIR laser irradiation; (C) the UV-vis absorption spectra of 5-FU solutions before (black) and after (red) nanocomposite loading and release (inset) at fixed times; (D) the release profiles of 5-FU loaded PANI@SiO₂ NPs with (black) and without (red) laser irradiation (2.47 W cm⁻², 808 nm).

5-Fluorouracil (5-FU) was selected as a representative anticancer drug for the investigation of the drug delivery capability of the yolk–shell nanostructured PANI@SiO₂ particles. Based on the peak intensity at 265 nm in the UV-vis spectra before and after the drug loading process, the loading content of 5-FU is 0.26 mg per mg PANI@SiO₂ (Fig. 4C). The photothermal effect of PANI@SiO₂ discussed above can stimulate drug release. Under conditions of pH 5.5, no significant release of 5-FU was observed at room temperature. However, after irradiating the system for 10 min, the release process became much quicker owing to the acceleration of desorption and delivery of the 5-FU from the yolk–shell nanostructured PANI@SiO₂ induced by the heating treatment (Fig. 4D). A two-step irradiation process was conducted on the sample with a control experiment carried out at room temperature. A higher release efficiency is observed upon laser irradiation than that in the system without photothermal treatment at the first 10 min and 1 h (7.7% vs. 3%), respectively (inset of Fig. 4C). After removing the laser, no apparent drug release occurs for either system. However, a continuing release is found upon laser treatment again for the first system, while the other one remains stable with no drug release. This illustrates the excellent photothermal property of the yolk–shell nanostructured PANI@SiO₂ for application in drug delivery.

4. Conclusions

In summary, yolk–shell nanostructured polyaniline@SiO₂ particles were synthesized using CeO₂ as a reactive template. The weak solubility of the CeO₂ core in the SiO₂ shell in acidic solution allowed the slow generation of Ce⁴⁺ ions that induced the confined polymerization of aniline diffusing across the SiO₂ layer. In order to achieve such uniform yolk–shell nanostructures, a well-established diffusion–polymerization rate equilibrium was realized by finely tuning the SiO₂ shell thickness, reaction temperature and aniline concentration. As a proof of concept, the drug delivery and photothermal release properties of the obtained samples were investigated. Such a unique synthesis strategy can be adopted to construct various complicated yolk–shell nanostructures.

Acknowledgements

The authors thank Jilin Provincial Science and Technology Development Foundation (Grant No. 20140101109JC) and National Natural Science Foundation of China (Grant No. 21103018) for financial support.

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Footnote

† Electronic supplementary information (ESI) available: Synthesis and characterization of the samples, kinetic UV-vis spectra of the system in the absence and presence of aniline; HRTEM images of CeO₂, CeO₂@SiO₂ and PANI@SiO₂ and the EDS of the former two; TEM images of polypyrrole@SiO₂ obtained at room temperature and 323 K. See DOI: 10.1039/c5ra15065e

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