Chinese Chemical Letters 29 (2018) 1725–1730

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Chinese Chemical Letters

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[29_TD$IF]Review

Au-Fe3O4 heterostructures for catalytic, analytical, and biomedical

applications
Baoling Liua , Hongchen Zhangb , Ya Dinga,*
a
Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, China
b
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

A R T I C L E I N F O [31_TD$IF]A B S T R A C T

Article history: Heterostructures are a series of nanomaterials combining different components into a single
Received 1 October 2018 nanostructure. Au-Fe3O4 heterostructures have received considerable attentions because of their
Received in revised form 2 December 2018 superior properties coming from both individual and combinational features of gold and iron oxide
Accepted 3 December 2018
nanoparticles. Their intrinsically peculiar magnetic, optical properties, and structure designability
Available online 5 December 2018
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
Keywords:
Au-Fe3O4 heterostructures and their potential applications in the biomedical field, focusing on the unique
Au-Fe3O4 heterostructures
Janus nanoparticles
synergistic effect caused by the combination of gold and iron oxide structures. This review will provide
Catalyst insights into the structure control in adjusting the function of heterogeneous or hybrid material, such as
Multimodal imaging Au-Fe3O4 heterostructures, to implement their biomedical applications.
Synergistic treatment © 2018 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.

1. Introduction nanoparticles, PB nanocubes coated with AuNPs, were developed

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-bis-pyrene@Si-PEG (Au-BP@SP), composed by
inorganic gold stars and organic bis-pyrene nanoaggregates, was
prepared to exert photothermal therapy [32_TD$IF](PTT) upon irradiation by
the laser beam (808 nm) and emit strong fluorescence occurred
from BP nanoaggregates [6]. Prussian blue (PB)@Au core-satellite
* Corresponding author.
E-mail address: dingya@cpu.edu.cn (Y. Ding).
to carry out [3_TD$IF]magnetic resonance imaging (MRI) and computed
tomography (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 bifunc-
tional 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 ([34_TD$IF]AuNRs), nanoshell, and nano-
spheres, AuNPs are also applied to achieve laser-induced PTT of
cancers [14]. CT scan makes use of computer-processed combi-
nations of X-ray measurements taken from different angles to
produce cross-sectional images of specific areas of a scanned
object [15,16]. Due to the high atomic number and X-ray
absorption coefficient of gold atom, AuNPs are considered as
desirable contrast agent for CT [17]. In addition, because of their
sufficiently large optical absorption to enhance the agent’s
photoacoustic signal, [35_TD$IF]AuNPs are also used in photoacoustic
imaging (PAI) [18].

https://doi.org/10.1016/j.cclet.2018.12.006
1001-8417/ © 2018 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
1726 B. Liu et al. / Chinese Chemical Letters 29 (2018) 1725–1730
Superparamagnetic iron oxide nanoparticles (IONPs, commonly
Fe3O4 NPs) are often used as the contrast agent of [36_TD$IF]MRI because of
its high relaxivity and contrast effect [19]. Directly guided by the
magnetic field, Fe3O4 NPs can also be applied to chemodynamic
therapy (CDT) via Fenton reaction under high H2O2 concentrations
in tumor [20]. Under alternating current (AC) magnetic field, Fe3O4
NPs can generate heat for the ablation of cancers [21,22].
The intrinsic appeal of Au-Fe3O4 heterostructures are inherited
not only from the unique properties of AuNPs or Fe3O4 NPs, but also
from their complementary function and synergistic effect. Firstly,
these two different nanoparticle domains supplied different
surfaces to be modified for multi-anchoring functionalization.
Next, the catalytic activity [23–28] and heat performance [29] of
Au-Fe3O4 heterostructures have been improved by increasing the
interface between gold and iron oxide surface. Moreover,
combining these two NPs into one system, multimodal imaging
of CT, PAI, and MRI can be achieved simultaneously [30,31] for
making up their individual technical shortcomings. Finally, the PTT
and chemotherapy of Au-Fe3O4 heterostructures and their con-
jugates would be more precise under the magnetic field guided
delivery [32,33]. Thus, the Au-Fe3O4 heterostructures show
excellent performance in [37_TD$IF]catalytic, analytical, and biomedical
applications, including, 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], [38_TD$IF]AuNPs were synthesized firstly
and then iron oxide epitaxially grew on the Au seeds. Dumbbell-
like bifunctional composite nanoparticles of Au-Fe3O4 with the
size tuned from 2 nm to 8 nm for Au and 4 nm to 20 nm for Fe3O4
were synthesized as the first proof of this double functional
nanostructure [35]. The shape and size were characterized by
transmission electron microscope (TEM, Fig. 1A). The strength of
metal-support bonding between gold nanoparticles and “nano-
engineered” Fe3O4 substrates was significantly related to the size
and morphology control of a metal oxide support [36]. The shape
and size were mainly affected by the temperature for the
nucleation and growth of nanoparticles, the ratio between Au
and Fe3O4, and the polarity of the solvent. The dumb-bell structure
offers an ideal model nanoparticle with two distinct surfaces and
functionalities for potential [39_TD$IF]applications.
[(Fig._1)TD$IG]
Fig. 1. (A) Oil phase synthesis of dumbbell-like Au-Fe3O4 dimers and their TEM images. Reprinted with permission [35]. Copyright 2005, American Chemical Society. (B)
Water phase synthesis of Fe3O4-supported Au NPs with satellite structure and their TEM images. Reprinted with permission [44]. Copyright 2014, Elsevier.
On the basis of above preparation method, the regulation on the
structure of either Au or Fe3O4 [40_TD$IF]NPs 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 Fe3O4 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 [35_TD$IF]AuNPs 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
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 [41_TD$IF]OH in the presence of Fe2+ species [48]. Due to
different surface energy of Au and Fe3O4, the electrons on the
contact interface of Au-Fe3O4 heterostructures are more active.
Associated with the magnetic property of Fe3O4, Au-Fe3O4
 B. Liu et al. / Chinese Chemical Letters 29 (2018) 1725–1730 1727
[(Fig._2)TD$IG]

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

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 nitro-
phenol to 4-aminophenol [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].
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

[(Fig._3)TD$IG]

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) High-resolution XPS spectra of Au-Fe3O4 NPs after
adsorption of 10 ppm As(III). Reprinted with permission [66]. Copyright 2018, American Chemical Society.
1728 B. Liu et al. / Chinese Chemical Letters 29 (2018) 1725–1730
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:[42_TD$IF]Fe3O4 is another impact factor in controlling
the catalytic capability of Au-Fe3O4 heterostructures. In the
photocatalytic reaction of methylene blue, Au-Fe3O4 heterostruc-
tures showed higher photocatalytic efficiency than pure Fe3O4 and
the higher concentration of AuNPs in the range from 1 wt% to 5 wt%
[60]. Moreover, after iron oxides were coated on the surface of
cetyltrimethylammonium bromide (CTAB)-capped [43_TD$IF]AuNRs, the
photocatalytic efficiency of Fe3O4 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 FexOy 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
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 [35_TD$IF]AuNPs 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 immo-
bilized 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)-1,2,3,4,5,6-hexanhydro-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 Fe3O4 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].
5. Au-Fe3O4 heterostructures in biomedical applications
5.1. Multimodal imaging
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 accu-
mulation in FA receptor-overexpressed cancer cells and were
further used as an efficient nanoprobe for dual mode CT/MR
imaging of a xenografted FAR-overexpressing 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 heterostruc-
tures, 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 [4_TD$IF]surface enhanced Raman spectroscopy (SERS) imaging in the
near infrared (NIR) biological window [75].
5.2. Combination therapy
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 [40_TD$IF]NPs, Au-
Fe3O4 heterostructures have two kinds of different surfaces, gold
and iron oxide, and show possibility to anchor drug molecules via
more types of interactions. The aptamer–siRNA chimera con-
structed by VEGF RNA aptamer and Notch3 siRNA was bonded with
cationic Au-Fe3O4 NPs through electrostatic interaction [79].
Herceptin and oxaliplatin can be conjugated to the surface of
PEG- and dopamine-modified Au- Fe3O4 NPs through a covalent
bond [80].
In order to improve the selective targeting capacity to tumor,
targeting and therapeutic moieties can be modified on the surface
of Au-Fe3O4 NPs simultaneously. Folate-conjugated gold shell
coated magnetite nanoparticles were synthesized to target cancer
cells with folate receptor that is overexpressed on the cell surface
[81]. When DNA aptamers targeting vascular endothelial growth
factor (VEGF) assembled onto the surface of Au-Fe3O4 by
electrostatic absorption, Apt-Au-Fe3O4 could be found to bind
 B. Liu et al. / Chinese Chemical Letters 29 (2018) 1725–1730
[(Fig._4)TD$IG]
Fig. 4. (A) Images of mice at various axial positions before and 5 min after
intratumoral injection of pDNA/Au@PDM/Fe3O4: overlay PAI images (left), T2-
weighted 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.
with SKOV-3 ovarian cancer cells with high selectivity [82]. For
delivering platin to Her2-positive tumor cells specifically, the
dumbbell-like Au-Fe3O4 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 combin-
ing the advantages of inorganic nanoparticles (e.g.,[45_TD$IF] imaging,
magnetic guided delivery, magnetic hyperthermia (MH) 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-co-acrylamide) [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
1729
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].
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, [46_TD$IF]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  C, thus killing tumor cells [93]. With the high magnetic
thermal conversion efficiency of Fe3O4 [21,22], Au-Fe3O4 hetero-
structures 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].
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 Fe3O4 surface and the superoxide
radical at the Au surface accelerated the generation of peroxyni-
trite, 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].
6. Conclusions
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 hetero-
structures is expected to improve the accuracy of surgical
navigation. Utilizing the magnetic targeting function of Fe3O4
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 [35_TD$IF]AuNPs and Fe3O4 NPs, the
structure combination of these two heterostructures provides an
excellent “all-in-one” system encompassing enhanced catalytic
activity, multimodal imaging, and combination therapy.
Acknowledgments
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. Interface 9 (2017) 8569–8580.
[2] R. Hao, J. Yu, Z.G. Ge, et al., Nanoscale 5 (2013) 11954–11963.
1730 B. Liu et al. / Chinese Chemical Letters 29 (2018) 1725–1730

[3] F. Oyarzun-Ampuero, A. Vidal, M. Concha, et al., Curr. Pharm. Des. 21 (2015) [49] C.J. Jin, J. Han, F.Y. Chu, X.X. Wang, R. Guo, Langmuir 33 (2017) 4520–4527.
4329–4341. [50] J. Liu, Z.W. Zhao, Z.X. Ding, Z.D. Fang, F.Y. Cui, RSC Adv. 6 (2016) 53080–53088.
[4] S. Wang, J. Lin, Z.T. Wang, et al., Adv. Mater. 29 (2017) 1701013. [51] F. Ke, L.H. Wang, J.F. Zhu, Nanoscale 7 (2015) 1201–1208.
[5] I. Schick, S. Lorenz, D. Gehrig, et al., J. Am. Chem. Soc. 136 (2014) 2473–2483. [52] J.C. Cheng, S.L. Zhao, W.B. Gao, P.B. Jiang, R. Li, React. Kinet. Mech. Catal. 121
[6] P.P. Yang, Y.G. Zhai, G.B. Qi, et al., Small 12 (2016) 5423–5430. (2017) 797–810.
[7] Y. Dou, X. Li, W.T. Yang, et al., ACS Appl. Mater. Interface 9 (2017) 1263–1272. [53] A. Fakhri, M. Naji, J. Photochem. Photobiol. B 167 (2017) 58–63.
[8] Q. Wu, Y.N. Lin, F.J. Wo, et al., Small 13 (2017)1701129. [54] Y.Y. Song, H.J. Jiang, H.K. Bi, et al., ACS Omega 3 (2018) 973–981.
[9] B. Ankudze, A. Philip, T.T. Pakkanen, Sensor. Actuat. B-Chem. 265 (2018) 668– [55] Y. Wang, H.B. Fang, Y.Z. Zheng, et al., Nanoscale 7 (2018) 19118–19128.
674. [56] T.Y. Lai, W.C. Lee, J. Photochem. Photobiol. A 204 (2009) 148–153.
[10] Y. Ding, Z. Jiang, K. Saha, et al., Mol. Ther. 22 (2014) 1075–1083. [57] Z. Li, X.B. Pan, T.L. Wang, et al., Nanoscale Res. Lett. 8 (2013) 96.
[11] J.J. Liang, Y.Y. Zhou, J. Wu, Y. Ding, Curr. Drug Met. 15 (2014) 620–631. [58] X.H. Feng, S.K. Zhang, X. Lou, Colloid Surf. B 107 (2013) 220–226.
[12] M.C. Daniel, D. Astruc, Chem. Rev. 104 (2004) 293–346. [59] L. Souza da Costa, D. Zanchet, Catal. Today 282 (2017) 151–158.
[13] C.M. Cobley, J. Chen, E.C. Cho, L.V. Wang, Y. Xia, Chem. Soc. Rev. 40 (2011) 44– [60] A. Mahmood, S.M. Ramay, Y.S. Al-Zaghayer, et al., Desalin. Water Treat. 57
56. (2015) 20069–20075.
[14] S.S. Xing, X.W. Zhang, L.Y. Luo, et al., Nanotechnology 29 (2018) 405101. [61] F.H. Lin, R.A. Doong, J. Phys. Chem. C 121 (2017) 7844–7853.
[15] J. Kirchner, L.M. Sawicki, F. Nensa, et al., Eur. J. Nucl. Med. Mol. Imaging 46 [62] Y.F. Chen, J. Hong, D.Y. Wu, et al., RSC Adv. 6 (2016) 8336–8345.
(2019) 437–445. [63] J.F. Zeng, L.H. Jing, Y. Hou, et al., Adv. Mater. 26 (2014) 2694–2698.
[16] B.W. Lan, X.J. Li, Acad. Radiol. (2018), doi:http://dx.doi.org/10.1016/j. [64] R. Chauhan, J. Singh, P.R. Solanki, et al., Biochem. Eng. J. 103 (2015) 103–113.
acra.2018.05.002. [65] J.C. Shen, Y. Yang, Y. Zhang, et al., Sensor. Actuat. B-Chem. 226 (2016) 512–517.
[17] K.T. Butterworth, S.J. McMahon, F.J. Currell, K.M. Prise, Nanoscale 4 (2012) [66] S.S. Li, W.Y. Zhou, M. Jiang, et al., Anal. Chem. 90 (2018) 4569–4577.
4830–4838. [67] J. Wei, S.S. Li, Z. Guo, et al., Anal. Chem. 88 (2016) 1154–1161.
[18] J.V. Jokerst, A.J. Cole, D. Van de Sompel, S.S. Gambhir, ACS Nano 6 (2012) [68] H. Zhang, X.T. Tian, Y. Shang, Y.H. Li, X.B. Yin, ACS Appl. Mater. Interface 10
10366–10377. (2018) 28390–28398.
[19] T. Wang, Y. Hou, B. Bu, et al., Small 14 (2018) 1800573. [69] R. Zhou, P. Bagga, K. Nath, et al., Cancer Res. 78 (2018) 5521–5526.
[20] C. Zhang, W.B. Bu, D.L. Ni, et al., Angew. Chem. Int. Ed. 55 (2016) 2101–2106. [70] X.H. Liu, C.H. Gao, J.H. Gu, et al., ACS Appl. Mater. Interface 8 (2016) 27622–
[21] K.S. Sharma, R.S. Ningthoujam, A.K. Dubey, et al., Sci. Rep. 8 (2018) 14766. 27631.
[22] G.K. Thirunavukkarasu, K. Cherukula, H. Lee, et al., Biomaterials 180 (2018) [71] J.Q. Xi, W.J. Wang, L.Y. Da, et al., ACS Biomater. Sci. Eng. 4 (2018) 1083–1091.
240–252. [72] J. Zhu, Y.J. Lu, Y.G. Li, et al., Nanoscale 6 (2014) 199–202.
[23] H. Kang, H.J. Jung, D.S.H. Wong, et al., J. Am. Chem. Soc. 140 (2018) 5909–5913. [73] W.J. Dong, Y.S. Li, D.C. Niu, et al., Small 9 (2013) 2500–2508.
[24] W. Shi, X.Y. Liu, C. Wei, et al., Nanoscale 7 (2015) 17249–17253. [74] M. Felber, R. Alberto, Nanoscale 7 (2015) 6653–6660.
[25] H.D. Cai, K.A. Li, J.C. Li, et al., Small 11 (2015) 4584–4593. [75] J. Reguera, D.J. de Aberasturi, M. Henriksen-Lacey, et al., Nanoscale 9 (2017)
[26] Q. Gao, Y. Xing, M.L. Peng, et al., Chin. J. Chem. 35 (2017)1700032. 9467–9480.
[27] F. Pang, R.F. Zhang, D.P. Lan, J.P. Ge, ACS Appl. Mater. Interface 10 (2018) 4929– [76] R.H. Jin, Z.N. Liu, Y.K. Bai, Y.S. Zhou, X. Chen, ACS Omega 3 (2018) 4306–4315.
4936. [77] S. Lee, A. Stubelius, N. Hamelmann, V. Tran, A. Almutairi, ACS Appl. Mater.
[28] L. Shang, Y.H. Liang, M.Z. Li, et al., Adv. Funct. Mater. 27 (2017) 1606215. Interface 10 (2018) 40378–40387.
[29] P. Guardia, S. Nitti, M.E. Materia, et al., J. Mater. Chem. B 5 (2017) 4587–4594. [78] S.H. Jeong, J.H. Jang, H.Y. Cho, Y.B. Lee, Arch. Pharm. Res. 41 (2018) 797–814.
[30] Y. Hu, J. Yang, P. Wei, et al., J. Mater. Chem. B 3 (2015) 9098–9108. [79] Y. Chen, M.J. Xu, Y. Guo, et al., Nanotechnology 28 (2017) 025101.
[31] J.C. Li, L.F. Zheng, H.D. Cai, et al., ACS Appl. Mater. Interface 5 (2013) 10357– [80] D.R. Liu, X.W. Li, C.L. Chen, et al., Oncol. Lett. 15 (2018) 8079–8087.
10366. [81] S. Karamipour, M.S. Sadjadi, N. Farhadyar, Spectrochim. Acta A 148 (2015) 146–
[32] J.R. Peng, T.T. Qi, J.F. Liao, et al., Theranostics 4 (2014) 678–692. 155.
[33] D. Yan, X. Liu, G. Deng, et al., J. Colloid Interface Sci. 530 (2018) 547–555. [82] Z. Jian, K.Y. Tu, Y.L. Liu, et al., Mater. Sci. Eng. C 80 (2017) 88–92.
[34] C. Wang, C.J. Xu, H. Zeng, S.H. Sun, Adv. Mater. 21 (2009) 3045–3052. [83] C. Xu, B. Wang, S. Sun, J. Am. Chem. Soc. 131 (2009) 4216–4217.
[35] H. Yu, M. Chen, P.M. Rice, et al., Nano Lett. 5 (2005) 379–382. [84] B.H. Wu, S.H. Tang, M. Chen, N.F. Zheng, Chem. Commun. 50 (2014) 174–176.
[36] C.W. Han, T. Choksi, C. Milligan, et al., Nano Lett. 17 (2017) 4576–4582. [85] J.F. Ren, S. Shen, Z.Q. Pang, et al., Chem. Commun. 47 (2011) 11692–11694.
[37] W.L. Shi, H. Zeng, Y. Sahoo, et al., Nano Lett. 6 (2006) 875–881. [86] X.J. Chen, G.L. Li, Q.H. Han, et al., Chemistry 23 (2017) 17204–17208.
[38] F.H. Lin, R.A. Doong, J. Colloid Interface Sci. 417 (2014) 325–332. [87] C.N. Wang, Y.Y. Wang, Y.L. Jin, et al., J. Nanosci. Nanotechnol. 15 (2015) 6784–
[39] Y.H. Wei, R. Klajn, A.O. Pinchuk, B.A. Grzybowski, Small 4 (2008) 1635–1639. 6789.
[40] J. Canet-Ferrer, P. Albella, A. Ribera, J.V. Usagre, S.A. Maier, Nanoscale Horiz. 2 [88] X.Y. Nan, X.J. Zhang, Y.Q. Liu, et al., ACS Appl. Mater. Interface 9 (2017) 9986–
(2017) 205–216. 9995.
[41] Y. Li, J.W. Zhao, W.L. You, D.H. Cheng, W.H. Ni, Nanoscale 9 (2017) 3925–3933. [89] C.M. Li, T. Chen, I. Ocsoy, et al., Adv. Funct. Mater. 24 (2014) 1772–1780.
[42] M.V. Efremova, V.A. Naumenko, M. Spasova, Sci. Rep. 8 (2018) 11295. [90] Y. Hu, Y.Q. Zhou, N.N. Zhao, F.S. Liu, F.J. Xu, Small 12 (2016) 2459–2468.
[43] X.O. Liu, M. Atwater, J.H. Wang, Q. Huo, Colloid. Surf. B 58 (2007) 3–7. [91] T. Suto, M. Ito, T. Uehara, et al., Int. Congress Ser. 1232 (2002) 383–388.
[44] F. Yan, R.Y. Sun, Mater. Res. Bull. 57 (2014) 293–299. [92] Z. Hedayatnasab, F. Abnisa, W.M.A.W. Daud, Mater. Des. 123 (2017) 174–196.
[45] Y. He, J.C. Liu, L.L. Luo, et al., Proc. Natl. Acad. Sci. U. S. A. 115 (2018) 7700–7705. [93] O.L. Gobbo, K. Sjaastad, M.W. Radomski, Y. Volkov, A. Prina-Mello, Theranostics
[46] R. Ye, A.V. Zhukhovitskiy, R.V. Kazantsev, et al., J. Am. Chem. Soc. 140 (2018) 5 (2015) 1249–1263.
4144–4149. [94] M.V. Efremova, Y.A. Nalench, E. Myrovali, et al., Beilstein J. Nanotechnol. 9
[47] M. Yang, L.F. Allard, M. Flytzani-Stephanopoulos, J. Am. Chem. Soc. 135 (2013) (2018) 2684–2699.
3768–3771. [95] S. Klein, C. Harreiss, C. Menter, et al., ACS Appl. Mater. Interface 10 (2018)
[48] Y.L. Dai, Z. Yang, S.Y. Cheng, et al., Adv. Mater. 30 (2018) 1704877. 17071–17080.