Au-Fe3O4 heterostructures for catalytic, analytical, and biomedical applications

Accepted Manuscript Title: Au-Fe3 O4 heterostructures for catalytic, analytical, and biomedical applications Authors: Baoling Liu, Hongchen Zhang, Ya Ding PII: DOI: Reference:

S1001-8417(18)30466-2 https://doi.org/10.1016/j.cclet.2018.12.006 CCLET 4743

To appear in:

Chinese Chemical Letters

Please cite this article as: Liu B, Zhang H, Ding Y, Au-Fe3 O4 heterostructures for catalytic, analytical, and biomedical applications, Chinese Chemical Letters (2018), https://doi.org/10.1016/j.cclet.2018.12.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Review

Au-Fe3O4 heterostructures for catalytic, analytical, and biomedical applications Baoling Liu a, Hongchen Zhang b, Ya Ding a,  a

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Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, China Beijing Key Laboratory of Magnetoelectric Materials and Devices (BKL-MEMD), Beijing Innovation Center for Engineering Science and Advanced Technology (BIC-ESAT), Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China b

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Graphical Abstract

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Au-Fe3O4 heterostructures including dumbbell-like dimer, core-shell structure, and flower-type nanoparticles (NPs), attract much attention due to their multiple modifiable surfaces and unique properties coming from either Au or Fe3O4 nanoparticles. This review focuses on the preparation methods and biomedical applications of these heterogenous NPs in the fields of catalysis, assay, multimodal imaging, and combination therapy.

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 Corresponding author. E-mail address: [email protected]

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ARTICLE INFO

ABSTRACT

Article history: Received 1 October 2018 Received in revised form 2 December 2018 Accepted 3 December 2018 Available online

Heterostructures are a series of nanomaterials combining different components into a single nanostructure. Au-Fe3O4 heterostructures have received considerable attentions because of their superior properties coming from both individual and combinational features of gold and iron oxide nanoparticles. Their intrinsically peculiar magnetic, optical properties, and structure designability greatly enhance and broaden their potential applications in catalysis, assay, multimodal imaging, and synergistic treatment for tumor. In this review, we systematically introduce the preparation methods of Au-Fe3O4 heterostructures and their potential applications in the biomedical field, focusing on the unique synergistic effect caused by the combination of gold and iron oxide structures. This review will provide insights into the structure control in adjusting the function of heterogeneous or hybrid material, such as Au-Fe3O4 heterostructures, to implement their biomedical applications.

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Keywords: Au-Fe3O4 heterostructures Janus nanoparticles Catalyst Multimodal imaging Synergistic treatment

1. Introduction

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Inorganic nanoparticles (NPs) and their oxides with various compositions, structures, and functions have been synthesized and widely used as contrast agents and drug vehicles [1,2]. Heterostructures composed of more than one kind of NPs, present unique physicochemical properties from different nanomaterials and provide “all-in-one” excellent performance [3]. Compared with single nanomaterial, it is facile to expand the potential functions and applications of nanomaterials with multi-compositions. Due to the complexity and heterogeneity of tumor tissue, multimodal diagnosis and multifunctionally therapeutic system attracts more attention than ever for precise detection and effective cocktail therapy [4]. Two-photon active silica-coated Au@MnO Janus particles were prepared by a seed-mediated nucleation for simultaneous magnetic and optical detection of tumor cells [5]. Au-bispyrene@Si-PEG (Au-BP@SP), composed by inorganic gold stars and organic bis-pyrene nanoaggregates, was prepared to exert photothermal therapy upon irradiation by the laser beam (808 nm) and emit strong fluorescence occurred from BP nanoaggregates [6]. Prussian blue (PB)@Au core-satellite nanoparticles, PB nanocubes coated with AuNPs, were developed to carry out MR-CT imaging and synergistic photothermal and radiosensitive therapy [7]. Similarly, dumbbell-like MnFe2O4–NaYF4 Janus nanoparticles was synthesized via a two-step thermolysis approach. This magnetic-luminescent nanocomposite combined functions of magnetic and luminescent materials that endow them bimodal imaging, magnetic field directed drug delivery, and imaging-guided cancer therapies [8]. Among these heterostructures, Au-Fe3O4 is one of the most important bifunctional heterostructures. Gold nanoparticles (AuNPs) are a widely used biomedical probes [9] and drug carriers [10,11] due to their controllable shape and size, flexible surface chemistry, adjustable optical properties, and biological inert [12,13]. Owing to the desirable photothermal performance of gold nanorods (GNRs), nanoshell, and nanospheres, AuNPs are also applied to achieve laser-induced photothermal therapy (PTT) of cancers [14]. Computed tomography (CT) scan makes use of computer-processed combinations of X-ray measurements taken from different angles to produce cross-sectional images of specific areas of a scanned object [15,16]. Due to the high atomic number and X-ray absorption coefficient of gold atom, AuNPs are considered as desirable contrast agent for CT [17]. In addition, because of their sufficiently large optical absorption to enhance the agent’s photoacoustic signal, Au NPs are also used in photoacoustic imaging (PAI) [18]. Superparamagnetic iron oxide nanoparticles (IONPs, commonly Fe 3O4 NPs) are often used as the contrast agent of magnetic resonance imaging (MRI) because of its high relaxivity and contrast effect [19]. Directly guided by the magnetic field, Fe3O4 NPs can also be applied to chemodynamic therapy (CDT) via Fenton reaction under high H2O2 concentrations in tumor [20]. Under alternating current (AC) magnetic field, Fe3O4 NPs can generate heat for the ablation of cancers [21,22]. The intrinsic appeal of Au-Fe3O4 heterostructures are inherited not only from the unique properties of AuNPs or Fe 3O4 NPs, but also from their complementary function and synergistic effect. Firstly, these two different nanoparticle domains supplied different surfaces to be modified for multi-anchoring functionalization. Next, the catalytic activity [23-28] and heat performance [29] of Au-Fe3O4 heterostructures have been improved by increasing the interface between gold and iron oxide surface. Moreover, combining these two NPs into one system, multimodal imaging of CT, PAI, and MRI can be achieved simultaneously [30,31] for making up their individual technical shortcomings. Finally, the PTT and chemotherapy of Au-Fe3O4 heterostructures and their conjugates would be more precise under the magnetic field guided delivery [32,33]. Thus, the Au-Fe3O4 heterostructures show excellent performance in biomedical applications, including catalysis, assay, multimodal imaging, and combination therapy. 2. Preparation of Au-Fe3O4 heterostructures The methods for the preparation of Au-Fe3O4 heterostructures can be divided into two categories, oil phase synthesis and aqueous phase synthesis. Using oil phase synthesis [34], Au nanoparticles were synthesized firstly and then iron oxide epitaxially grew on the Au seeds. Dumbbell-like bifunctional composite nanoparticles of Au-Fe3O4 with the size tuned from 2 nm to 8 nm for Au and 4 nm to 20 nm for Fe3O4 were synthesized as the first proof of this double functional nanostructure [35]. The shape and size were characterized by transmission electron microscope (TEM, Fig. 1A). The strength of metal-support bonding between gold nanoparticles and “nano-

Please donot adjust the margins engineered” Fe3O4 substrates was significantly related to the size and morphology control of a metal oxide support [36]. The shape and size were mainly affected by the temperature for the nucleation and growth of nanoparticles, the ratio between Au and Fe 3O4, and the polarity of the solvent. The dumb-bell structure offers an ideal model nanoparticle with two distinct surfaces and functionalities for potential biomedical applications. (B)

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Fig. 1. (A) Oil phase synthesis of dumbbell-like Au-Fe3O4 dimers and their TEM images. Reprinted with permission [35]. Copyright 2005, American Chemical Society. (B) Water phase synthesis of Fe3O4-supported Au NPs with satellite structure and their TEM images. Reprinted with permission [44]. Copyright 2014, Elsevier Science Direct.

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On the basis of above preparation method, the regulation on the structure of either Au or Fe 3O4 nanoparticles offers possible property modulation of Au-Fe3O4 nanostructure [37,38]. Increasing the molar ratio of iron precursor, such as Fe(CO) 5, to gold, dumbbell-like morphologies of the dimer NPs can be changed into flowers having two to six Fe 3O4 leaves around the gold core [39]. Increasing in the reaction time enlarged individual iron oxide domains and generated particles with smaller gold and larger Fe3O4. Further modulation of the molar ratio between iron and gold precursors produced the Au-Fe3O4 and Fe3O4-Au core-shell morphologies [40,41]. For obtaining superior in vitro and in vivo T2 relaxivity for magnetic resonance imaging, 25 nm octahedral-shaped Fe3O4 magnetite nanocrystals are epitaxially grown on 9 nm Au seed nanoparticles using a modified wet-chemical synthesis [42]. Oleylamine-stabilized Au NPs as prepared firstly [43]. After that Fe3O4 is grown on the Au seed particles referred to a previous method [35,39] with some modifications. 1-Octadecene was replaced by phenyl ether and the reaction time was increased from 45 min to 3 h allowing for a full crystallization process. The strongly improved crystallinity and a highly facetted growth mode characterized by X-ray diffraction (XRD) patterns led to a better T2 contrast in MRI as compared to other hybrids or commercial materials. Ultraviolet-visible spectroscopy declared the existence of Au NPs and curves of hysteresis loops revealed the magnetism of Au-Fe3O4 heterostructures. The simultaneous functionalization of fluorescence dyes and drugs on two different surfaces offered an all-in-one platform for theranostics. In the case of aqueous phase synthesis, Fe3O4 NPs were generally synthesized at first by thermal decomposition under relatively high temperature and pressure using ferric chloride as raw material and trisodium citrate as stabilizer [44]. And then, chloroauric acid was subsequently reduced on the surface of Fe3O4 NPs by sodium borohydride to form Au-Fe3O4 heterostructures (Fig. 1B). 3. Au-Fe3O4 heterostructures in catalytic applications

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AuNPs show high catalysis selectivity towards CO oxidation [45], oxidation of hydrocarbons [46], and water-gas shift reactions [47], while Fe3O4 NPs display peroxidase-like activity that activates H2O2 to produce ·OH in the presence of Fe2+ species [48]. Due to different surface energy of Au and Fe3O4, the electrons on the contact interface of Au-Fe3O4 heterostructures are more active. Associated with the magnetic property of Fe3O4, Au-Fe3O4 heterostructures not only exhibit synergistic catalytic ability with higher activity [49,50], but also are able to be separated magnetically for recycling (Fig. 2). The catalytic activity of Au-Fe3O4 heterostructures with various structures has been widely studied. The bifunctional Fe3O4/Au heterostructures with core-satellites structures exhibited high performance in catalytic reduction of 4-nitrophenol [44]. The designed Au-Fe3O4@metalorganic framework (MOF) catalysts showed excellent functions in rapid catalytic reduction of nitrophenol to 4aminophenol [51]. The Au/Fe3O4@hTiO2 nanospheres exhibited favorable catalytic performance in both the photodegradation of Rhodamine B (RhB) under visible light irradiation and the catalytic reduction of 4-nitrophenol to 4-aminophenol by sodium borohydride at room temperature [52]. Because most of photocatalytic processes is highly oxidative, lethal to most microorganisms [53-55], photocatalysis is used to kill not only pathogens, but also cancer cells [56-58].

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Fig. 2. (A) The mechanism of catalytic degradation of 4-chlorophenol by Au-Fe3O4 heterostructures and (B) the catalytic degradation of 4chlorophenol by all test systems. Reprinted with permission [50]. Copyright 2016, Royal Society of Chemistry.

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The catalytic efficiency of Au-Fe3O4 heterostructures is related to many factors. The increase of interfaces between Au and FexOy caused by the redox pretreatments improved the catalytic performance of Au-FexOy dumbbells nanoparticles in CO oxidation [59]. After the pretreatment, FexOy shells suffered great morphological and structural changes, becoming irregular and presenting lower crystallinity, which enhanced the interface in Au-FexOy and subsequently was of benefit for the catalytic activity. The amount ratio of Au: Fe3O4 is another impact factor in controlling the catalytic capability of Au-Fe3O4 heterostructures. In the photocatalytic reaction of methylene blue, Au-Fe3O4 heterostructures showed higher photocatalytic efficiency than pure Fe 3O4 and the higher concentration of AuNPs in the range from 1 wt% to 5 wt% [60]. Moreover, after iron oxides were coated on the surface of cetyltrimethylammonium bromide (CTAB)-capped gold nanorods (AuNRs), the photocatalytic efficiency of Fe 3O4 was about 1.7-fold higher than Fe2O3 as more surface defects were present on the Fe3O4 shell. This result demonstrated the impact of oxidation state of Fe xOy in promoting the adsorption and activation of reagents on the surface during the catalytic reactions [41]. In addition, the catalytic efficiency showed close relationship with the particle size of the Au core and the substituent groups of the substrate. For the reduction of nitroarenes by Au@Fe3O4 yolk-shell nanocatalyst, small-sized Au core NPs (e.g., 2.5 nm) in the yolk-shell nanostructures exhibited superior catalytic performance for nitroarene reduction. The reduction rates of nitroarenes with electron-withdrawing groups were found to be 2.3-2.6 times higher than those with electron-donating groups [61]. 4. Au-Fe3O4 heterostructures in analytic applications

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Taking advantages of heterogeneous surface of Au-Fe3O4 heterostructures, more different specific moieties can be modified on their surface. The S-Au bond stabilized on Au NPs surface [62] and diphosphate, hydroxamate, or catechol decorated on Fe3O4 surface [63] facile the connection of multi-modifiers, and the magnetic properties of Fe3O4 NPs offer easy separation by magnetic fields. Thus, Au-Fe3O4 heterostructures were widely applied to detect the related substances. Based on the combined the optical, electrochemical, and magnetic properties of Au-Fe3O4 heterostructures, some toxic substances in foods or water can be detected. A primary monoclonal anti-aflatoxin antibody (anti AFB1) covalently immobilized on a monolayer modified gold coated quartz crystal electrode (anti AFB1/4-ATP/Au) by 4-amino thiophenol. The secondary rabbit-immunoglobulin antibodies (r-IgGs) tagged with core-shell structure of gold coated iron oxide nanoparticles (r-IgG-Au-Fe3O4) were used to achieve the sandwiched system and the regeneration of the bioelectrode. This immuno sensor could regenerate about 15-16 times with 2%-3% loss of activity. Using the electrochemical quartz crystal microbalance-cyclic voltammetry technology, the prepared immuno electrode was highly promising for detection of AFB1 in food, such as corn flakes samples [64]. In addition, l-(2-mercaptoethyl)-1,2,3,4,5,6hexanhydro-s-triazine-2,4,6-trione (MTT) modified Au-Fe3O4 heterostructures was explored for the bimodal detection of melamine. The bimodal detection was based on the aggregation of Au-Fe3O4@MTT NPs from the dispersed state upon the formation of special triple hydrogen bonds between melamine and MTT. This phenomenon caused the red shift of the absorption peak and the increase of the spin–spin relaxation time (T2) of the water protons upon addition of melamine, which enhanced the detection selectivity toward melamine in foods [65]. Furthermore, heavy metals in water could be also detected by Au-Fe3O4 NP-fabricated systems. For As(III) detection, Au-Fe3O4 NPs was modified the screen-printed carbon electrode to serve as an efficient sensing interface. The signals were attributed to the participation of Fe(II)/Fe(III) cycle on Fe 3O4 NPs surface in the electrochemical reaction of As(III) redox. The formation of dumbbell-like Au-Fe3O4 NPs by adding Au NPs can accelerate the redox electrocatalysis of As(III), and subsequently enhanced the electrochemical response (Fig. 3) [66,67].

Fig. 3. (A) Schematic representation of detected As(III) by Au-Fe3O4 heterostructures and (B) HRTEM images of Au-Fe3O4. (C) Comparison of sensitivities for SWASV detection of As(III) at ~7 nm Au, ~10 nm Fe3O4, and Au-Fe3O4 SPCE. The inset compares limit of detection of test samples (LODs). (D) Highresolution XPS spectra of Au-Fe3O4 NPs after adsorption of 10 ppm As(III). Reprinted with permission [66]. Copyright 2018, American Chemical Society.

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5. Au-Fe3O4 heterostructures in biomedical applications 5.1 Multimodal imaging

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Multimodality imaging of tumor tissues is important in the diagnosis and precise surgical navigation for tumor treatment. MRI is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body in both health and disease. Fe3O4 NPs are the commonly used contract agent for MRI to reflect the chemical structure information in human tissues. It has great superiority for early diagnosis of tissue necrosis, malignant disease and degenerative diseases, which makes the contrast of soft tissue more accurate [68,69]. AuNPs are considered as desirable contrast agent for CT and PAI [70,71]. Embracing both AuNPs and Fe3O4 NPs, Au-Fe3O4 heterostructures featuring a magneto-plasmonic structure show their multimodal imaging ability [72]. It has also reported that folic acid (FA)-modified Au–Fe3O4 heterostructures increased the specific accumulation in FA receptoroverexpressed cancer cells and were further used as an efficient nanoprobe for dual mode CT/MR imaging of a xenografted FARoverexpressing tumor model [25]. In addition, adding other imaging agent in the system of Au- Fe3O4 heterostructures would offer multimodal imaging functions. When adding fluorescent reagent into the Au-Fe3O4 heterostructures, it could not only simultaneously enhance the contrast effect for both MR and CT imaging, but also be effective for both dark-field light scattering and fluorescence imaging [73]. Attaching [99mTc(CO)3]+ fragment on the surface of either Fe3O4–Au core–shell or Fe3O4–Au dumbbell-like NPs, single photon emission computed tomography (SPECT) imaging could be also achieved [74]. Besides adding imaging probes, adjusting the structure of nanocomposite can also affect its imaging function [49]. Compared with Au-Fe3O4 shell-core NPs, the Janus dimer of Au- Fe3O4 offered high availability of the iron oxide surface, which consequently gave rise to high r2 relaxivity values and the exposed iron oxide part could facilitate the reaction of potassium ferrocyanide with iron atoms, giving rise to blue staining of the sample where the nanoparticles were located. In addition, the Janus NPs composed of a branched gold nanostar could extend their use in photoacoustic and SERS imaging in the NIR biological window [75]. 5.2 Combination therapy

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Taking advantages of the leaky tumor blood vessels, NPs tend to accumulate in tumor tissues via the enhanced permeability and retention (EPR) effect. In recent years, various NPs have been employed as promising carriers for the delivery of small molecule and gene drugs [76-78]. Different from the homogeneous nanoparticles, Au-Fe3O4 heterostructures have two kinds of different surfaces, gold and iron oxide, and show possibility to anchor drug molecules via more types of interactions. The aptamer–siRNA chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with cationic Au-Fe3O4 NPs through electrostatic interaction [79]. Herceptin and oxaliplatin can be conjugated to the surface of PEG- and dopamine-modified Au‑ Fe3O4 NPs through a covalent bond [80]. In order to improve the selective targeting capacity to tumor, targeting and therapeutic moieties can be modified on the surface of Au-Fe3O4 NPs simultaneously. Folate-conjugated gold shell coated magnetite nanoparticles were synthesized to target cancer cells with folate receptor that is overexpressed on the cell surface [81]. When DNA aptamers targeting vascular endothelial growth factor (VEGF) assembled onto the surface of Au-Fe3O4 by electrostatic absorption, Apt-Au‑ Fe3O4 could be found to bind with SKOV-3 ovarian cancer cells with high selectivity [82]. For delivering platin to Her2-positive tumor cells specifically, the dumbbell-like AuFe3O4 were functionalized with thiol-modified platin complexes on the Au domain, and with herceptin on the Fe3O4 domain [83]. In this case, Herceptin can treat metastatic breast cancer as an antibody drug. In addition, it also helps the preferred targeting of platin complexes to Sk-Br3 cells that are Her2-positive breast cancer cells as opposed to Her2-negative MCF-7 breast cancer cells. Inorganic heterogeneous nanoparticles are capable of combining the advantages of inorganic nanoparticles (e.g.. imaging, magnetic guided delivery, magnetic hyperthermia for magnetic nanoparticles or photoablation therapy for plasmonic nanoparticles) with drug delivery/therapy, which is highly attractive to theranostics [28,40,84]. The structure of Au-Fe3O4 heterostructures can be adjusted to proper optical properties to obtain high photothermal conversion efficiency of AuNPs [85,86]. Irradiated by the laser, the Au-Fe3O4 heterostructures can generate heat and raise the local temperature. This is beneficial for the release of drugs embedded in thermosensitive materials, such as the release of Ampicillin from AuNPs decorated Fe3O4@poly(N-isopropylacrylamide-coacrylamide) [87]. Although chemotherapy is one of the most important approach in cancer treatment, it is limited by drug resistance and systematic toxicity. Based on the attractive photothermal effect of plasmonic nanomaterials, the combination of photothermal agents and chemotherapy is a promising approach to achieve enhanced cancer killing efficiency through the synergistic effect [88]. As such, Fe3O4@Au nanorose was fabricated. The inner Fe3O4 core functioned as the MR imaging agent. The photothermal effect was achieved through near-infrared absorption by the gold shell, and simultaneously facilitated the release of the anticancer drug doxorubicin (Dox) loaded by Fe3O4@Au nanoroses [89]. For synergistic PTT and gene therapy, polycationic Au nanorod (NR)-coated Fe3O4 nanosphere (Au@pDM/Fe3O4, pDM representing poly(2-dimethyl amino)ethyl methacrylate) was used to compress plasmid DNA into pDNA/Au@pDM/Fe3O4. The combined near-infrared absorbance properties of Fe3O4-PDA and AuNR-pDM were applied to photoacoustic imaging and photothermal therapy, which achieved a trimodal imaging and combined photothermal and gene therapy in a xenografted rat glioma nude mouse model (Fig. 4) [90].

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Due to the limited ability of near-infrared light in the penetration of tissues, the treatment effect of PTT for tumors located deeply in tissues would be weaken [91]. However, magnetic hyperthermia (MH) demonstrated the advantages of hyperthermia for deep tumors in tissues [92]. Under the AC, the magnetic particles injected into the tumor site can generate heat and raised the local temperature to above 42 oC, thus killing tumor cells [93]. With the high magnetic thermal conversion efficiency of Fe 3O4 [21,22], AuFe3O4 heterostructures can exert hyperthermia at the edge and in the deep of tumors by combining PTT with MH [33]. It has been reported recently that Au-Fe3O4 heterostructures with the size of 25 nm showed the best thermal efficiency under AC [94].

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Fig. 4. (A) Images of mice at various axial positions before and 5 min after intratumoral injection of pDNA/Au@PDM/Fe 3O4: overlay PAI images (left), T2weighted MRI images (middle), CT images (right), where the tumor regions are indicated by the white circles, (B) infrared thermal images (at different time points), (C) the tumor growth curves, and (D) photographs of dissected tumors after various treatments of two weeks. Reprinted with permission [90]. Copyright 2016, Wiley Online Library.

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6. Conclusions

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In addition, for the dumbbell-like Au-Fe3O4 dimer, combining a plasmonic nanosphere with a highly reactive Fe3O4 surface, may significantly enhance the impact of X-rays on tumor tissue. So, nitrosyl tetrafluoroborate was modified on the surface of dimer by the ligand exchange to enabled the X-ray-induced NO release. The production of NO radical at the Fe 3O4 surface and the superoxide radical at the Au surface accelerated the generation of peroxynitrite, and then caused DNA strand breaks and the nitration of various proteins. It was the example of Au-Fe3O4 dimer in the application of X-ray-enhanced radiation therapy [95].

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Heterostructures integrate the properties and functions of various components in one platform, which greatly enhance and expand the potential applications of these heterogeneous or hybrid materials. This review introduces the preparation methods and biomedical applications of Au-Fe3O4 heterostructures in recent years. Au-Fe3O4 heterostructures enhance catalytic activity of AuNPs when the interface between Au and Fe3O4 increased. The multimodal imaging of MRI, CT, and PAI by Au-Fe3O4 heterostructures is expected to improve the accuracy of surgical navigation. Utilizing the magnetic targeting function of Fe 3O4 NPs, drug loaded on Au-Fe3O4 NPs could be delivered precisely, and then released effectively with the help of photothermal conversion of Au or magnetic thermal conversion of Fe3O4. Based on the individual functions coming from Au NPs and Fe 3O4 NPs, the structure combination of these two heterostructures provides an excellent “all-in-one” system encompassing enhanced catalytic activity, multimodal imaging, and combination therapy. Acknowledgment This work was supported by grants from the National Natural Science Foundation of China (Nos. 31870946, 31470916). We thank Prof. Yanglong Hou at Perking University for his guidance on writing this article. References [1] T. Cui, J. J. Liang, H. Chen, et al., ACS Appl. Mater. Interf. 9 (2017) 8569-8580. [2] R. Hao, J. Yu, Z. G. Ge, et al., Nanoscale 5 (2013) 11954-11963. [3] F. Oyarzun-Ampuero, A. Vidal, M. Concha, et al., Curr. Pharm. Des. 21 (2015) 4329-4341. [4] S. Wang, J. Lin, Z.T. Wang, et al., Adv. Mater. 29 (2017) 1701013.

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