Article

pubs.acs.org/accounts

Nanocontainers in and onto Nanofibers

Shuai Jiang,† Li-Ping Lv,†,‡ Katharina Landfester,* and Daniel Crespy*,‡
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
*
S Supporting Information

CONSPECTUS: Hierarchical structure is a key feature explaining the superior properties of

many materials in nature. Fibers usually serve in textiles, for structural reinforcement, or as
support for other materials, whereas spherical micro- and nanoobjects can be either highly
functional or also used as fillers to reinforce structure materials. Combining nanocontainers
with fibers in one single object has been used to increase the functionality of fibers, for
example, antibacterial and thermoregulation, when the advantageous properties given by the
encapsulated materials inside the containers are transferred to the fibers. Herein we focus our
discussion on how the hierarchical structure composed of nanocontainers in nanofibers yields
materials displaying advantages of both types of materials and sometimes synergetical effects.
Such materials can be produced by first carefully designing nanocontainers with defined
morphology and chemistry and subsequently electrospinning them to fabricate nanofibers. This
method, called colloid-electrospinning, allows for marrying the properties of nanocontainers
and nanofibers. The obtained fibers could be successfully applied in different fields such as
catalysis, optics, energy conversion and production, and biomedicine.
The miniemulsion process is a convenient approach for the encapsulation of hydrophobic or hydrophilic payloads in
nanocontainers. These nanocontainers can be embedded in fibers by the colloid-electrospinning technique. The combination of
nanocontainers with nanofibers by colloid-electrospinning has several advantages. (1) The fiber matrix serves as support for the
embedded nanocontainers. For example, through combining catalysts nanoparticles with fiber networks, the catalysts can be
easily separated from the reaction media and handled visually. This combination is beneficial for the reuse of the catalyst and the
purification of products. (2) Electrospun nanofibers containing nanocontainers offer the active agents inside the nanocontainers a
double protection by both the fiber matrix and the nanocontainers. Since the polymer of the fibers and the polymer of the
nanocontainers have usually opposite polarities, the encapsulated substance, for example, catalysts, dyes, or drugs, can be
protected against a large variety of environmental influences. (3) Electrospun nanofibers exhibit unique advantages for tissue
engineering and drug delivery that are a structural similarity to the extracellular matrix of biological tissues, large specific surface
area, high and interconnected porosity which enhances cell adhesion, proliferation, drug loading, and mass transfer properties, as
well as the flexibility in selecting the raw materials. Moreover, the nanocontainer-in-nanofiber structure allows multidrug loading
and programmable release of each drug, which are very important to achieve synergistic effects in tissue engineering and disease
therapy.
The advantages offered by these materials encourage us to further understand the relationship between colloidal properties and
fibers, to predict the morphology and properties of the fibers obtained by colloid-electrospinning, and to explore new possible
combination of properties offered by nanoparticles and nanofibers.

1. INTRODUCTION grafting chitosan-gelatin microcapsules containing patchouli oil

In nature and in synthetic products, fibers are usually employed
in textiles or as structure materials whereas spherical micro- and
nanoobjects can be either highly functional or also reinforce
structure materials when they are used as fillers. The
combination of fibers and particles in one single object has
been used to increase the functionality of fibers and is still a
classical field of research in textile science. The fibers serve as
anchoring points for microcapsules for the storage of phase
change materials and flame retardants, or as platforms for the
delivery of pharmaceuticals, fragrances, herbicides, pesticides,
fungicides, and insecticides.
The combination of microcapsules and fibers has proven to
be useful when the advantageous properties given by the
encapsulated material inside the microcapsules are transferred
to the fibers. Antibacterial properties were given to fabrics by
to cotton fabrics with the help of a coupling agent.1 As another
example, n-hexadecane was encapsulated in polymer micro-
capsules that were applied on cotton and cotton/polyester
fabrics.2 The fabrics displayed thermoresponsive properties and
allowed for a thermoregulation near the skin.
We discuss here how the hierarchical structure presented by
nanocontainers embedded in nanofibers yields either to
materials displaying advantages of both types of materials, or
even to materials displaying a synergetic effect instead of a
simple sum of the properties from both components. The use
of nanoarchitectonics requires methods to produce well-defined
and controlled structures that are described below.
Received: November 30, 2015

© XXXX American Chemical Society A DOI: 10.1021/acs.accounts.5b00524

Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research
2. PREPARATION METHODS
2.1. Synthesis of Nanocontainers
Although there are many different methods to prepare
nanocontainers, few exist that allow for the formation of
nanocontainers with a liquid core that can be oily or aqueous.
The miniemulsion process is typically used for producing
nanoparticles with sizes ranging from 30 to 500 nm. Because
the droplets are stable and can be directly used as independent
templates for reactions such as sol−gel processes3 and
polymerizations4 or physical processes such as the evaporation
of a solvent,5 the structure and size of the individual
nanoparticles can be very well-controlled (Figure S1a). The
size distribution of the obtained nanoparticles vary significantly
depending mainly on the reaction and type and concentration
of stabilizer.4 Functional payloads can be used as part of the
dispersed phase forming the droplets and then be encapsulated
directly in the core of nanocontainers. The complexity in the
nanostructure can be associated with various chemical
functionalities such as controlled delivery of encapsulated
payloads upon external stimuli (Figure S1b).6 This can be
achieved by employing materials that are stimuli-responsive as
the shell of nanocapsules7,8 or creating nanocapsules with
stimuli-responsive liquid cores.9 The layer-by-layer method is
also interesting but the formation of nanocontainers requires
normally the presence of a nanoparticulate substrate that is
subsequently removed by calcination or dissolution.10 The
interior of the nanocontainer is then loaded by soaking the
nanocontainers with a medium containing the species to be
encapsulated. The process is therefore demanding because it
requires many steps that are the sequential deposition of
oppositively charged polyelectrolytes followed by the loading of
the nanocontainers. Other interesting techniques for the
fabrication of nanocontainers are the “Ouzo effect” or
nanoprecipitation,11 and the formation of lipid-based col-
loids.12−14 The latter is promising because many different
internal morphologies can be achieved (see the Supporting
Information). Finally, hollow inorganic nanoparticles represent
another platform for the encapsulation of payloads.15 They
have found applications as catalysts, for lithium-ion batteries, as
gas sensors, and as drug-delivery nanocarriers.
2.2. Electrospinning
The electrospinning process is a method to produce micro- and
nanofibers from an electrified liquid. A liquid meniscus is
charged by the application of an electric field and stretched to
form a thin liquid jet that is ejected toward a collector. The
liquid can be for instance a polymer solution in which the
solvent evaporates during the flight of the jet or a polymer melt.
The formation of a continuous jet instead of droplets as it
occurs in electrospray is ensured by the presence of
entanglements in the polymer solution that is spun. The fibers
diameters are usually between 10 nm and 10 μm and can be
controlled by the electrospinning parameters and polymer
concentration. Depending on the formulation and the electro-
spinning parameters, the fibers appearance can be smooth or
rough, porous, flattened or cylindrical. Similarly as what was
previously described for larger fibers, nanoparticles can be
deposited or grown on nanofibers produced by electrospinning.
For instance, it was possible to crystallize ceria and titania
nanoparticles on the surface of fibers by first electrospinning
the fibers, then soaking the fibers in medium containing cerium
ion, and finally soaking in another medium to create the desired
metal oxides.16 The fibers’ surface can present chemical
B DOI: 10.1021/acs.accounts.5b00524
Article
functionalities acting as ligand for metal ions. Thus, carboxylic
acid group in carboxymethyl cellulose or phosphonate groups
in a copolymer of styrene and vinyl phosphonate were used as
anchoring groups for silver17 and cerium or titanium ions,16
respectively. The materials have however the drawback to be
usually produced at least in three steps.
A variant of the standards solution- or melt-electrospinning
process is the so-called colloid-electrospinning method, for
which nano- or microparticles, nano- or microcapsules, rods
and tubes, or small emulsion droplets that are in a colloidal
dispersion are electrospun (TOC Figure).18,19 Because electro-
spinning of emulsions is a very mild process,20 it allows for the
encapsulation of enzymes that remain active in the fibers21 or
for the encapsulation of temperature sensitive substances such
as volatile fragrances.22 When water-in-oil emulsions are spun,
hydrophilic payloads can be delivered from hydrophobic fibers
and the release profile can be adjusted by the nanostructures
inside the fibers.23,24 A very interesting consequence of using
colloid-electrospinning for embedding nanocontainers in nano-
fibers is that the polymer of the nanofibers and the polymer of
the nanocontainers have usually opposite polarities. The
advantage is that payloads of opposite polarities can be
simultaneously loaded in the fiber matrix and in the
nanocontainers.
The fibers can be particularly difficult to characterize,
especially when the nanocontainers and the nanofibers are
produced from polymers. Fluorescence microscopy was
employed to clearly identified nano- and microparticles in
electrospun fibers.25,26 Super-resolution fluorescence techni-
ques were used to measure nanoparticles as small as 100 nm in
diameter in nanofibers.27 Both nanofibers and nanoparticles can
be labeled and measured by dual-color stimulation emission
depletion microscopy (STED);27 additionally the anisotropy of
stretched nanoparticles in nanofibers templates can be also
determined.28 The localization of nanoparticles in/on the fibers
is determined by the electrospinning conditions, the interfacial
tension between polymer solution/particles, and the surface
tensions of the polymer solution and the particles. Jo et al.
demonstrated that core−sheath fibers with a core enriched with
particles could be obtained with a high concentration of
particles and with good wettability of the particles by the
polymer solution.25 They could increase the wettability by
lowering the interfacial tension between polymer solution and
particles by using microgels that were swollen. Furthermore,
the solvent pressure was also found to play a role in the
distribution of silica inside polystyrene fibers.29
3. FIBERS AS SUPPORT FOR NANOCONTAINERS
Fiber matrixes can act as a support for the nanocontainers that
are embedded inside in many areas such as energy storage,
catalysis, and biomedical application. One example are carbon
nanofibers (CNFs) loaded with SnSb nanoparticles as anode
materials of lithium-ion battery.30 CNFs acted as protective
layer and support matrix for the carbon-coated SnSb nano-
particles. Improved electrochemical stability of the anode
materials was then obtained. Similarly to what was described
previously for large fibers, electrospun fibers with nano-
containers can be also used for thermoregulation. For example,
methacrylate-based nanocapsules with n-hexadecane as core
were electrospun in the presence of poylacrylonitrile that build
the fibers matrix.31
Nanoparticles are widely used in catalysis applications mainly
due to their large ratio of surface area to volume. However,
Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research Article

Figure 1. (a) Scheme of the preparation of metal oxide/silica fibers. (b) SEM micrograph of a LiCoO2/SiO2 fiber obtained by calcination at 600 °C.
(C) Schematic representation of the simple geometrical model used to calculate percent volume of LiCoO2/SiO2 nanoparticles. Reproduced with
permission from ref 34. Copyright 2012 American Chemical Society.

Figure 2. Schematic illustration of fibers as the support (a) for the alignment of TiO2 nanoparticles in catalytic application (Reproduced with
permission from ref 35. Copyright 2010 American Chemical Society) and (b) for polymerization of ethylene (Reproduced with permission from ref
38. Copyright 2014 Wiley-VCH Verlag GmbH & Co. KGaA).

catalyst nanoparticles are usually difficult to remove completely
from the reacting medium after service. Residual nanostructural
catalysts may cause secondary pollution, that is, pollution from
the nanostructured catalyst itself, if they are not removed
completely.32 Centrifugation, which is a common method to
separate the dispersed phase from the continuous phase of
dispersions, was shown to be detrimental to the structural
integrity of polymer nanocapsules.33 Incorporating nano-
particles in/on nanofibers produced by electrospinning
provides a new pathway for catalyst preparation. The advantage
of combining nanoparticles with fiber networks is that fibers
can be easily separated from the reaction media and handled
visually, which is beneficial for the reuse of the catalyst and the
purification of products.16 However, the catalyst should be
predominantly located at the surface of the fibers to avoid the
detrimental effect of having the polymer covering the active
sites of the catalyst.
In catalysis, the fiber matrix acts also as a structural
framework to improve the mechanical properties of the
catalyst.34 Ceria fibers fabricated by calcinating electrospun
nanofibers composed of a polymer template and a cerium salt
were not mechanically stable. The nanofibers could retain
structural integrity by incorporating silica nanoparticles. Indeed,
the silica nanoparticles were sintered during calcination and
acted as structural framework for the nucleated ceria nano-
particles (Figure 1).
The fibers can be used to align catalysts nanoparticles35,36 or
as electronic contact between embedded nanoparticles.37 The
alignment of TiO235 (Figure 2a) and CdS-PdS36 nanoparticles
induced by their electrospinning contributed to an efficient
C DOI: 10.1021/acs.accounts.5b00524
charge separation through interparticle charge transfer along
the nanofibers framework. As a result, the photocatalytic
activity of the aligned nanoparticles was higher than of
nonaligned nanoparticles. In another example, carbon/CeO2
composite nanofibers were used as support for PtRu catalyst
nanoparticles for methanol oxidation. The intimate contact
between the carbon and CeO2 nanoparticles promoted the
catalytic property of PtRu nanoparticles.37
Moreover, fibers as reaction template were also used for
olefin polymerizations (Figure 2b). 38 Functionalized
polystyrene nanoparticles were electrospun with poly(vinyl
alcohol) (PVA) to generate anisotropic nanofibers as support
for polymerization of ethylene. After immobilizing activated
metallocene on the fibers, polymerization of ethylene along the
fibers was achieved. This strategy allowed the production of
polyolefin fibers using the replication effect of the support’s
shape without further processing. Electrospun fibers also
display support properties for tissue engineered scaffolds in
which the mechanical property can be improved by the fibers
network.39,40 Regenerated natural polymers used for scaffolds
usually display better biocompatibility and immunogenicity but
weaker mechanical strength compared with synthetic polymers.
Through electrospinning these polymers with synthetic
polymers, the mechanical property of formed fibrous scaffolds
can be enhanced.41,42
4. DOUBLE PROTECTION BY DOUBLE
ENCAPSULATION
Electrospun nanofibers containing nanocontainers offer the
active agents inside the nanocontainers a double protective
Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research
Figure 3. Illustration of how four kinds of growth factors were loaded, either directly embedded in HA and Col nanofibers or encapsulated in GNs
and then incorporated into nanofibers. Reproduced with permission from ref 43. Copyright 2014 Elsevier.
function (DPF), that is, the payloads or active agents are
protected by both the fiber’s matrix and the shell of the
nanocontainers. DPF becomes increasingly important in carrier
systems for as drugs and growth factors.43−47 Drugs display
toxicity at certain concentrations when exposed directly to the
biological tissues. Furthermore, growth factors, which are
usually proteins, may lose their bioactivity over a short time.
Therefore, the encapsulation of these substances in nano-
containers hinders direct contact with the unwanted tissues and
maintains their bioactivity.
By using DPF, it is also possible to preserve the activity of
upconversion dyes by protecting them from oxygen. Wohnhaas
et al. electrospun a dispersion of nanocapsules loaded with
upconversion dyes.48 PVA, which is known for its oxygen
barrier property, was used as fibers matrix. No significant
differences in upconversion intensity were observed when
compared it to samples that were stored in oxygen-free
atmosphere. The preserved activity of upconversion dye under
ambient atmosphere was attributed to the DPF.
5. ENHANCING CONTROLLED RELEASE OF
PAYLOADS
The development of nanocontainers that can deliver
therapeutic molecules such as antibiotics, anticancer drugs,
growth factors, DNA, and RNA to a targeted site remains a
challenge for biomedical applications. A variety of nano-
containers have been accordingly developed, for example,
micelles, dendrimers, liposomes, nanoparticles, nanocapsules,
and nanofibers.49 Among them, nanofibers fabricated by the
electrospinning technology exhibit unique advantages for tissue
engineering and drug delivery that are (a) a structural similarity
to the extracellular matrix of biological tissues; (b) a high
surface area to volume ratio; (c) a high and interconnected
porosity of electrospun meshes which can enhance cell
adhesion, proliferation, drug loading, and mass transfer
properties; and (d) a large flexibility in selecting the raw
materials to be spun.
Drug release from electrospun nanofibers can be controlled
by the architecture, porosity, and composition of nanofibers.
The affinity between the drug and the nanocontainer plays also
an important role. Based on different electrospinning
D DOI: 10.1021/acs.accounts.5b00524
Article
techniques and nanofiber structures, drug loading is often
achieved by three approaches: Coating, entrapment in the
fibers, and encapsulation by coaxial and emulsion electro-
spinning or loading nanocontainers in fibers,50 the latter being
the subject of interest here. In nanofibers produced by
electrospinning blends of drug/polymer solutions, the drug is
dispersed in the polymer matrix and therefore is subjected to
burst drug release.51 Core−sheath fibers, prepared by emulsion-
and coaxial-electrospinning,52,53 were found to effectively
hinder the initial burst release and achieve sustained release
profiles. However, the surfactant used in emulsion-electro-
spinning is difficult to remove and may introduce biocompat-
ibility issues. In the coaxial-electrospinning approach, the
selection of solvent for the inner solution and the control of
the spinning parameters are problematic to obtain core−sheath
fibers of high quality, especially when a water-soluble polymer is
required to be spun into the inner core.54
Taking into account both the processability and control over
the release profiles, novel drug delivery systems were developed
through a synergistic combination of nanocontainers and
electrospun nanofibers. In this case, the electrospun fibrous
matrix serves as a second barrier for the release of payloads.
For example, coaxial electrospun core−sheath nanofibers
with embedded liposomes were constructed as a drug delivery
system.55 Liposomes loaded with dextran functionalized with
fluorescein isothiocyanate (FITC-dextran) remained intact in
the PVA core/poly-ε-caprolactone sheath nanofibers which
showed a reduced initial burst release and prolonged release. In
the case of core−sheath nanofibers with liposomes, only ∼20%
of the FITC-dextran was detected after 24 h compared with an
intense burst release (∼61% release in the first 24 h) from
core−sheath fibers without liposomes. The release half-time
increased from tr = 20 h (without liposomes) to 120 h (with
liposomes).
The aforementioned study showed that single-drug release
can be effectively retarded by the fibers matrix that acts as a
second barrier. Moreover, multidrug loading and programmable
release of each drug are important to achieve synergistic effects
in tissue engineering and disease therapy.56,57
A large research areas in drug delivery is the targeted and
controlled release of anticancer drugs. For cancer treatment,
Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research
combination therapy is a promising strategy to improve the
therapeutic efficacy of drugs and reduce their side effects due to
the toxicity of a single drug at high dosage and the drug
resistance of cancer cells.45 A codelivery system loaded with
two or more anticancer drugs has been proposed to minimize
the dosage of drugs and to achieve synergistic therapeutic effect
in cancer therapy. Poly(lactic-co-glycolic acid) (PLGA)
composite nanofibers embedded with doxorubicin/mesoporous
silica nanoparticles and camptothecin/hydroxyapatite nano-
particles were developed for anticancer applications.45 In vitro
release studies indicated that the loaded drugs exhibited a
sustained release behavior from the nanofibers. Importantly, the
loaded nanofibers displayed a superior capacity of inhibiting
HeLa cells compared to the single drug loaded PLGA
nanofibers, which may result from the synergistic effect of the
doxorubicin and camptothecin.
Wound dressings are widely used for wound healing. Ideal
wound dressings are expected to exhibit a burst drug release at
the initial stage and then a sustained drug release for a long
period. The initial drug release is helpful for suppressing
infections and relieving pain of a wound in the early stage.
Meanwhile, sustained drug release is also very important for a
long-term protection of the wound without changing the
wound dressing.41 A skin equivalent substitute composed of
collagen (Col) and hyaluronic acid (HA) interstacking
nanofibers were designed for staged release of multiple
angiogenic factors for chronic wound healing (Figure 3).43
Vascular endothelial growth factor (VEGF), platelet-derived
growth factor (PDGF), basic fibroblast growth factor (bFGF),
and endothelial growth factor (EGF) were either directly
embedded in the nanofibers or encapsulated in the gelatin
nanoparticles (GNs). The GNs were then embedded in fibers
matrix. The delivery of EGF and bFGF in the early stage was
expected to accelerate epithelialization and vasculature
sprouting while the release of PDGF and VEGF in the late
stage aimed at inducing blood vessels maturation. This
designed particle-in-fiber structure allowed for a sustained
release of growth factors up to 1 month.
An interesting type of nanocontainer are halloysite
aluminosilicate nanotubes. They have been used for the loading
and subsequent release of hydrophilic biocides and corrosion
inhibitors.58 The loading proceeds usually by mixing a dry
powder of halloysite with a saturated solution of a substance to
be entrapped. The main advantages of halloysites nanotubes
over carbon nanotubes are that they are much cheaper and
biocompatible. The tubes can be coated with responsive
polymers via the layer-by-layer method to allow payloads to be
released upon an external trigger.59 Halloysites nanotubes could
be successfully electrospun and used to release the tetracycline
drug. The incorporation of hallyosites in the fibers was found to
hinder burst release of the drug and significantly increased the
tensile strength of the fibers.60
Another field where electrospun nanofibers have emerged as
interesting and useful materials is tissue engineering. In the case
of bone reconstruction, the electrospun nanofibrous scaffold
shows potential properties meeting the golden rules of bone
tissue engineering, for example, three-dimensional, highly
porous, and interconnected structures as well as fabrication
from degradable and biocompatible raw biomaterials.61
Sequential supplementation of growth factors was proved to
be useful to prevent the dedifferentiation of cells by first
promoting proliferation with one specific growth factor and
then inducing the differentiation and expression of a desired
E DOI: 10.1021/acs.accounts.5b00524
Article
phenotype by another growth factor.62 Ideally, bioactive growth
factors should be delivered in a controlled and sustained
manner without loss of their bioactivity. Bovine serum albumin
(BSA) nanoparticles were embedded in electrospun poly(ε-
caprolactone)-co-poly(ethylene glycol) (PCE) nanofiber scaf-
fold for controlled dual delivery of bone morphogenetic
protein-2 (BMP-2) and dexamethasone (DEX).63 BMP-2 was
encapsulated in BSA nanoparticles to maintain its bioactivity.
Nanofibers were then obtained by coelectrospinning of the
blending solution composed of the BSA nanoparticles, DEX,
and PCE copolymer. The bioactivity of DEX and BMP-2 was
preserved in the nanofibrous scaffold. In vitro studies showed a
sequential release pattern in which most of the DEX was
released in the initial 8 days and the BMP-2 release lasted up to
35 days.
6. CONCLUSIONS AND PERSPECTIVES
The possible combination of properties offered by nano-
particles and nanofibers are still largely unexplored. An obvious
advantage for the embedding of nanoparticles in fibers in that
the materials produced is macroscopic and therefore can be
easily separated from any liquid media. It is also less subjected
to safety issues related to nanoparticles in the environment
because the nanoparticles are embedded in the fibers. The
possibility to protect catalysts, dyes, or drugs thanks to a double
encapsulation strategy is very attractive when the fibers are
produced by colloid-electrospinning because the polarity of the
fibers matrix and the nanoparticles matrix is usually opposite
and therefore the encapsulated substance can be protected
against a large variety of environmental hazards. Apart from the
double protection of encapsulated substance which is a passive
property, the fibers display a set of active properties if the
materials of the nanoparticles and fibers matrix are stimuli-
responsive. In this field, advances taking advantage of
nanotechnology have been reported concerning textiles with
reduced friction treated with plasma,64 textiles for thermoreg-
ulation and humidity management based on temperature-
responsive polymers,65 and fibers as optical sensors for
temperature changes.66
Colloid-electrospinning from aqueous dispersions allows for
the fabrication of hydrophobic fibers from water-borne systems,
which is not the case for solution-spinning, for instance. The
aqueous dispersions are dispersed in a solution of a hydrophilic
polymer that can be subsequently extracted after the fabrication
of the fibers by electrospinning.67,68 This method represents
therefore an environmentally responsible alternative for the
processing of hydrophobic polymers.
The simultaneous cospinning of several dispersions offers the
possibility to prepare fibers with various compartments inside
them. By embedding nanoparticles that are organic and
inorganic in fibers, pores can be introduced by the selective
removal of the organic material for instance by calcination.
Nanopores to micropores can be then created by the
incorporation of sacrificial compartments in the fibers.69,70
In drug delivery, the combination of stimuli-responsive
behaviors from nanocontainers and nanofibers could lead to
fibers with very complicated release profiles that could be tuned
and adapted to the patient and the environmental conditions of
use. Finally, the relationship between colloidal properties and
fibers morphology is still largely not understood and only
empirical data are available at the moment that are specific to
the described experiments. There is still a long way to go to be
able to predict the morphology and properties of the fibers
Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research
obtained by colloid-electrospinning. However, the advantages
offered by these materials make it worth pursuing it.
■ Doctoral Promotion Program (DPP)”.
ASSOCIATED CONTENT
*
S Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.ac-
counts.5b00524.
Details for miniemulsion for the formation of nano-
containers and formation of lipid-based colloids; addi-
tional references (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
*E-mail: crespy@mpip-mainz.mpg.de.
*E-mail: landfester@mpip-mainz.mpg.de.
Present Address
‡ Nanoparticles and Nanocapsules. Adv. Polym. Sci. 2013, 262, 329−344.
(L.-P.L.) Department of Chemical Engineering, School of
Environmental and Chemical Engineering, Shanghai University,
Shangda Road 99, 200444, Shanghai, P. R. China. (D.C.)
Vidyasirimedhi Institute of Science and Technology, 555 Moo
1 Payupnai, Wangchan, Rayong 21210, Thailand.
Author Contributions
† Chem. Soc. 2013, 135, 14198−14205.
S.J. and L.-P.L. contributed equally to this work.
Notes
The authors declare no competing financial interest.
Biographies
Shuai Jiang studied chemical engineering at the University of Yantai,
China. In 2011, he entered the Institute of Coal Chemistry of the
Chinese Academy of Sciences. In 2013, he joined the Max Planck
Institute for Polymer Research via the CAS-MPG Doctoral Promotion
Programme.
Li-Ping Lv obtained her MEng degree in polymer science from the
Zhejiang University in 2011. She completed her PhD in 2014 under
the supervision of Prof. Landfester and Dr. Crespy in the Max Planck
Institute for Polymer Research in Mainz and joined Shanghai
University since 2015. Her current research interests include materials
for anticorrosion and energy storage" after "Polymer Research in
Mainz.
Katharina Landfester studied chemistry at the Technical University of
Darmstadt. In 1995, she received her doctoral degree after working
with Prof. H. W. Spiess at the Max Planck Institute for Polymer
Research. She moved for a postdoctoral stay at the Lehigh University
(Prof. M. El-Aasser). She returned to Germany in 1998, joining the
group of Prof. M. Antonietti at the Max Planck Institute of Colloids
and Interfaces in Golm. In 2003, she accepted a chair of full professor
of Macromolecular Chemistry at the University of Ulm. Since 2008,
she is director at the Max Planck Institute for Polymer Research.
Daniel Crespy studied chemistry at the University of Groningen and
Strasbourg. He joined Professor Katharina Landfester to complete a
PhD in the University of Ulm. In 2006, he held a position as project
leader at Empa (Swiss Federal laboratories for Materials Research and
Technology). He joined the Max Planck Institute for Polymer
Research in July 2009 as group leader. His current research interests
are the synthesis of new self-healing materials by heterophase
polymerizations and the colloid-electrospinning technique.
F DOI: 10.1021/acs.accounts.5b00524
Article
■ ACKNOWLEDGMENTS
We acknowledge the financial support from “MPG-CAS Joint
■
REFERENCES
(1) Liu, J.; Liu, C.; Liu, Y.; Chen, M.; Hu, Y.; Yang, Z. Study on the
Grafting of Chitosan−Gelatin Microcapsules onto Cotton Fabrics and
Its Antibacterial Effect. Colloids Surf., B 2013, 109, 103−108.
(2) Alay, S.; Göde, F.; Alkan, C. Synthesis and Thermal Properties of
Poly (N-Butyl Acrylate)/N-Hexadecane Microcapsules Using Differ-
ent Cross-Linkers and Their Application to Textile Fabrics. J. Appl.
Polym. Sci. 2011, 120, 2821−2829.
(3) Fickert, J.; Rupper, P.; Graf, R.; Landfester, K.; Crespy, D. Design
and Characterization of Functionalized Silica Nanocontainers for Self-
Healing Materials. J. Mater. Chem. 2012, 22, 2286−2291.
(4) Crespy, D.; Landfester, K. Miniemulsion Polymerization as a
Versatile Tool for the Synthesis of Functionalized Polymers. Beilstein J.
Org. Chem. 2010, 6, 1132−1148.
(5) Staff, R. H.; Landfester, K.; Crespy, D. Recent Advances in the
Emulsion Solvent Evaporation Technique for the Preparation of
(6) Zhao, Y.; Lv, L.-P.; Jiang, S.; Landfester, K.; Crespy, D. Advanced
Stimuli-Responsive Polymer Nanocapsules with Enhanced Capabilities
for Payloads Delivery. Polym. Chem. 2015, 6, 4197−4205.
(7) Lv, L.-P.; Zhao, Y.; Vilbrandt, N.; Gallei, M.; Vimalanandan, A.;
Rohwerder, M.; Landfester, K.; Crespy, D. Redox Responsive Release
of Hydrophobic Self-Healing Agents from Polyaniline Capsules. J. Am.
(8) Vimalanandan, A.; Lv, L.-P.; Tran, T. H.; Landfester, K.; Crespy,
D.; Rohwerder, M. Redox-Responsive Self-Healing for Corrosion
Protection. Adv. Mater. 2013, 25, 6980−6984.
(9) Zhao, Y.; Landfester, K.; Crespy, D. CO2 Responsive Reversible
Aggregation of Nanoparticles and Formation of Nanocapsules with an
Aqueous Core. Soft Matter 2012, 8, 11687−11696.
(10) Caruso, F.; Caruso, R. A.; Möhwald, H. Nanoengineering of
Inorganic and Hybrid Hollow Spheres by Colloidal Templating.
Science 1998, 282, 1111−1114.
(11) Ganachaud, F.; Katz, J. L. Nanoparticles and nanocapsules
created using the Ouzo effect: Spontaneous emulsification as an
alternative to ultrasonic and high-shear devices. ChemPhysChem 2005,
6, 209−216.
(12) Yaghmur, A.; de Campo, L.; Sagalowicz, L.; Leser, M. E.;
Glatter, O. Emulsified Microemulsions and Oil-Containing Liquid
Crystalline Phases. Langmuir 2005, 21, 569−577.
(13) Mulet, X.; Boyd, B. J.; Drummond, C. J. Advances in drug
delivery and medical imaging using colloidal lyotropic liquid crystalline
dispersions. J. Colloid Interface Sci. 2013, 393, 1−20.
(14) Martiel, I.; Sagalowicz, L.; Handschin, S.; Mezzenga, R. Facile
Dispersion and Control of Internal Structure in Lyotropic. Langmuir
2014, 30, 14452−14459.
(15) Hu, J.; Chen, M.; Fang, X.; Wu, L. Fabrication and application
of inorganic hollow spheres. Chem. Soc. Rev. 2011, 40, 5472−5491.
(16) Horzum, N.; Mari, M.; Wagner, M.; Fortunato, G.; Popa, A.-M.;
Demir, M. M.; Landfester, K.; Crespy, D.; Muñoz-Espí, R. Controlled
Surface Mineralization of Metal Oxides on Nanofibers. RSC Adv. 2015,
5, 37340−37345.
(17) Fu, J.; Li, D.; Li, G.; Huang, F.; Wei, Q. Carboxymethyl
Cellulose Assisted Immobilization of Silver Nanoparticles onto
Cellulose Nanofibers for the Detection of Catechol. J. Electroanal.
Chem. 2015, 738, 92−99.
(18) Crespy, D.; Friedemann, K.; Popa, A. M. Colloid-Electro-
spinning: Fabrication of Multicompartment Nanofibers by the
Electrospinning of Organic or/and Inorganic Dispersions and
Emulsions. Macromol. Rapid Commun. 2012, 33, 1978−1995.
(19) Bannwarth, M.; Crespy, D. Combining the Best of Two Worlds:
Nanoparticles and Nanofibers. Chem. - Asian J. 2014, 9, 2030−2035.
Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research
(20) Xu, X.; Zhuang, X.; Chen, X.; Wang, X.; Yang, L.; Jing, X.
Preparation of Core-Sheath Composite Nanofibers by Emulsion
Electrospinning. Macromol. Rapid Commun. 2006, 27, 1637−1642.
(21) Murase, S. K.; Lv, L.-P.; Kaltbeitzel, A.; Landfester, K.; del Valle,
L. J.; Katsarava, R.; Puiggali, J.; Crespy, D. Amino Acid-Based Poly
(Ester Amide) Nanofibers for Tailored Enzymatic Degradation
Prepared by Miniemulsion-Electrospinning. RSC Adv. 2015, 5,
55006−55014.
(22) Camerlo, A.; Bühlmann-Popa, A.-M.; Vebert-Nardin, C.; Rossi,
R. M.; Fortunato, G. Environmentally Controlled Emulsion Electro-
spinning for the Encapsulation of Temperature-Sensitive Compounds.
J. Mater. Sci. 2014, 49, 8154−8162.
(23) Qi, H.; Hu, P.; Xu, J.; Wang, A. Encapsulation of Drug
Reservoirs in Fibers by Emulsion Electrospinning: Morphology
Characterization and Preliminary Release Assessment. Biomacromole-
cules 2006, 7, 2327−2330.
(24) Yazgan, G.; Popa, A.; Rossi, R.; Maniura-Weber, K.; Puigmartí-
Luis, J.; Crespy, D.; Fortunato, G. Tunable Release of Hydrophilic
Compounds from Hydrophobic Nanostructured Fibers Prepared by
Emulsion Electrospinning. Polymer 2015, 66, 268−276.
(25) Jo, E.; Lee, S.; Kim, K. T.; Won, Y. S.; Kim, H. S.; Cho, E. C.;
Jeong, U. Core-Sheath Nanofibers Containing Colloidal Arrays in the
Core for Programmable Multi-Agent Delivery. Adv. Mater. 2009, 21,
968−972.
(26) Beck-Broichsitter, M.; Thieme, M.; Nguyen, J.; Schmehl, T.;
Gessler, T.; Seeger, W.; Agarwal, S.; Greiner, A.; Kissel, T. Novel
’Nano in Nano’ Composites for Sustained Drug Delivery: Biodegrad-
able Nanoparticles Encapsulated into Nanofiber Non-Wovens. Macro-
mol. Biosci. 2010, 10, 1527−1535.
(27) Friedemann, K.; Turshatov, A.; Landfester, K.; Crespy, D.
Characterization via Two-Color STED Microscopy of Nanostructured
Materials Synthesized by Colloid Electrospinning. Langmuir 2011, 27,
7132−7139.
(28) Herrmann, C.; Turshatov, A.; Crespy, D. Fabrication of Polymer
Ellipsoids by the Electrospinning of Swollen Nanoparticles. ACS
Macro Lett. 2012, 1, 907−909.
(29) Ding, B.; Lin, J.; Wang, X.; Yu, J.; Yang, J.; Cai, Y. Investigation
of Silica Nanoparticle Distribution in Nanoporous Polystyrene Fibers.
Soft Matter 2011, 7, 8376−8383.
(30) Niu, X.; Zhou, H.; Li, Z.; Shan, X.; Xia, X. Carbon-Coated SnSb
Nanoparticles Dispersed in Reticular Structured Nanofibers for
Lithium-Ion Battery Anodes. J. Alloys Compd. 2015, 620, 308−314.
(31) Alay, S.; Göde, F.; Alkan, C. Preparation and Characterization of
Poly (Methylmethacrylate-Coglycidyl Methacrylate)/N-Hexadecane
Nanocapsules as a Fiber Additive for Thermal Energy Storage. Fibers
Polym. 2010, 11, 1089−1093.
(32) Panthi, G.; Barakat, N. A.; Khalil, K. A.; Yousef, A.; Jeon, K.-S.;
Kim, H. Y. Encapsulation of CoS Nanoparticles in PAN Electrospun
Nanofibers: Effective and Reusable Catalyst for Ammonia Borane
Hydrolysis and Dyes Photodegradation. Ceram. Int. 2013, 39, 1469−
1476.
(33) Fickert, J.; Makowski, M.; Kappl, M.; Landfester, K.; Crespy, D.
Efficient Encapsulation of Self-Healing Agents in Polymer Nano-
containers Functionalized by Orthogonal Reactions. Macromolecules
2012, 45, 6324−6332.
(34) Horzum, N.; Muñoz-Espí, R.; Glasser, G.; Demir, M. M.;
Landfester, K.; Crespy, D. Hierarchically Structured Metal Oxide/
Silica Nanofibers by Colloid Electrospinning. ACS Appl. Mater.
Interfaces 2012, 4, 6338−6345.
(35) Choi, S. K.; Kim, S.; Lim, S. K.; Park, H. Photocatalytic
Comparison of TiO2 Nanoparticles and Electrospun TiO2 Nanofibers:
Effects of Mesoporosity and Interparticle Charge Transfer. J. Phys.
Chem. C 2010, 114, 16475−16480.
(36) Unnithan, A. R.; Barakat, N. A.; Nirmala, R.; Al-Deyab, S. S.;
Kim, H. Y. Novel Electrospun Nanofiber Mats as Effective Catalysts
for Water Photosplitting. Ceram. Int. 2012, 38, 5175−5180.
(37) Feng, C.; Takeuchi, T.; Abdelkareem, M. A.; Tsujiguchi, T.;
Nakagawa, N. Carbon−CeO2 Composite Nanofibers as a Promising
G DOI: 10.1021/acs.accounts.5b00524
Article
Support for a PtRu Anode Catalyst in a Direct Methanol Fuel Cell. J.
Power Sources 2013, 242, 57−64.
(38) Joe, D.; Golling, F. E.; Friedemann, K.; Crespy, D.; Klapper, M.;
Mullen, K. Anisotropic Supports in Metallocene-Catalyzed Polymer-
izations: Templates to Obtain Polyolefin Fibers. Macromol. Mater. Eng.
2014, 299, 1155−1162.
(39) Agarwal, S.; Wendorff, J. H.; Greiner, A. Use of Electrospinning
Technique for Biomedical Applications. Polymer 2008, 49, 5603−
5621.
(40) Kanani, A. G.; Bahrami, S. H. Review on Electrospun
Nanofibers Scaffold and Biomedical Applications. Trends Biomater.
Artif. Organs 2010, 24, 93−115.
(41) Liang, D.; Hsiao, B. S.; Chu, B. Functional Electrospun
Nanofibrous Scaffolds for Biomedical Applications. Adv. Drug Delivery
Rev. 2007, 59, 1392−1412.
(42) Stevens, M. M.; George, J. H. Exploring and Engineering the
Cell Surface Interface. Science 2005, 310, 1135−1138.
(43) Lai, H. J.; Kuan, C. H.; Wu, H. C.; Tsai, J. C.; Chen, T. M.;
Hsieh, D. J.; Wang, T. W. Tailored Design of Electrospun Composite
Nanofibers with Staged Release of Multiple Angiogenic Growth
Factors for Chronic Wound Healing. Acta Biomater. 2014, 10, 4156−
4166.
(44) Hou, Z.; Li, X.; Li, C.; Dai, Y.; Ma, P.; Zhang, X.; Kang, X.;
Cheng, Z.; Lin, J. Electrospun Upconversion Composite Fibers as
Dual Drugs Delivery System with Individual Release Properties.
Langmuir 2013, 29, 9473−9482.
(45) Chen, M. X.; Feng, W.; Lin, S.; He, C. L.; Gao, Y.; Wang, H. S.
Antitumor Efficacy of a PLGA Composite Nanofiber Embedded with
Doxorubicin@MSNs and Hydroxycamptothecin@HANPs. RSC Adv.
2014, 4, 53344−53351.
(46) Wei, J. C.; Hu, J.; Li, M.; Chen, Y.; Chen, Y. W. Multiple Drug-
Loaded Electrospun PLGA/Gelatin Composite Nanofibers Encapsu-
lated with Mesoporous ZnO Nanospheres for Potential Postsurgical
Cancer Treatment. RSC Adv. 2014, 4, 28011−28019.
(47) Liu, S.; Qin, M.; Hu, C.; Wu, F.; Cui, W.; Jin, T.; Fan, C.
Tendon Healing and Anti-Adhesion Properties of Electrospun Fibrous
Membranes Containing bFGF Loaded Nanoparticles. Biomaterials
2013, 34, 4690−4701.
(48) Wohnhaas, C.; Friedemann, K.; Busko, D.; Landfester, K.;
Baluschev, S.; Crespy, D.; Turshatov, A. All Organic Nanofibers as
Ultralight Versatile Support for Triplet−Triplet Annihilation Upcon-
version. ACS Macro Lett. 2013, 2, 446−450.
(49) Ganta, S.; Devalapally, H.; Shahiwala, A.; Amiji, M. A Review of
Stimuli-Responsive Nanocarriers for Drug and Gene Delivery. J.
Controlled Release 2008, 126, 187−204.
(50) Wang, Y.; Qiao, W.; Wang, B.; Zhang, Y.; Shao, P.; Yin, T.
Electrospun Composite Nanofibers Containing Nanoparticles for the
Programmable Release of Dual Drugs. Polym. J. 2011, 43, 478−483.
(51) Li, Z.; Kang, H. L.; Che, N.; Liu, Z. J.; Li, P. P.; Li, W. W.;
Zhang, C.; Cao, C.; Liu, R. G.; Huang, Y. Controlled Release of
Liposome-Encapsulated Naproxen from Core-Sheath Electrospun
Nanofibers. Carbohydr. Polym. 2014, 111, 18−24.
(52) Agarwal, S.; Greiner, A. On the Way to Clean and Safe
ElectrospinningGreen Electrospinning: Emulsion and Suspension
Electrospinning. Polym. Adv. Technol. 2011, 22, 372−378.
(53) Yarin, A. Coaxial Electrospinning and Emulsion Electrospinning
of Core−Shell Fibers. Polym. Adv. Technol. 2011, 22, 310−317.
(54) Liao, Y.; Zhang, L.; Gao, Y.; Zhu, Z.-T.; Fong, H. Preparation,
Characterization, and Encapsulation/Release Studies of a Composite
Nanofiber Mat Electrospun from an Emulsion Containing Poly(Lactic-
Co-Glycolic Acid). Polymer 2008, 49, 5294−5299.
(55) Mickova, A.; Buzgo, M.; Benada, O.; Rampichova, M.; Fisar, Z.;
Filova, E.; Tesarova, M.; Lukas, D.; Amler, E. Core/Shell Nanofibers
with Embedded Liposomes as a Drug Delivery System. Biomacromo-
lecules 2012, 13, 952−962.
(56) Lehár, J.; Krueger, A. S.; Avery, W.; Heilbut, A. M.; Johansen, L.
M.; Price, E. R.; Rickles, R. J.; Short Iii, G. F.; Staunton, J. E.; Jin, X.;
et al. Synergistic Drug Combinations Tend to Improve Therapeutically
Relevant Selectivity. Nat. Biotechnol. 2009, 27, 659−666.
Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research Article

(57) Woodcock, J.; Griffin, J. P.; Behrman, R. E. Development of

Novel Combination Therapies. N. Engl. J. Med. 2011, 364, 985−987.
(58) Lvov, Y. M.; Shchukin, D. G.; Möhwald, H.; Price, R. R.
Halloysite Clay Nanotubes for Controlled Release of Protective
Agents. ACS Nano 2008, 2, 814−820.
(59) Shchukin, D. G.; Lamaka, S. V.; Yasakau, K. A.; Zheludkevich,
M. L.; Ferreira, M. G. S.; Mohwald, H. Active anticorrosion coatings
with halloysite nanocontainers. J. Phys. Chem. C 2008, 112, 958−964.
(60) Qi, R. L.; Guo, R.; Shen, M. W.; Cao, X. Y.; Zhang, L. Q.; Xu, J.
J.; Yu, J. Y.; Shi, X. Y. Electrospun poly(lactic-co-glycolicacid)/
halloysite nanotube composite nanofibers for drug encapsulation and
sustained release. J. Mater. Chem. 2010, 20, 10622−10629.
(61) Pham, Q. P.; Sharma, U.; Mikos, A. G. Electrospinning of
Polymeric Nanofibers for Tissue Engineering Applications: A Review.
Tissue Eng. 2006, 12, 1197−1211.
(62) Jaklenec, A.; Hinckfuss, A.; Bilgen, B.; Ciombor, D. M.; Aaron,
R.; Mathiowitz, E. Sequential Release of Bioactive IGF-I and TGF- β1
from PLGA Microsphere-Based Scaffolds. Biomaterials 2008, 29,
1518−1525.
(63) Li, L.; Zhou, G. L.; Wang, Y.; Yang, G.; Ding, S.; Zhou, S. B.
Controlled Dual Delivery of BMP-2 and Dexamethasone by
Nanoparticle-Embedded Electrospun Nanofibers for the Efficient
Repair of Critical-Sized Rat Calvarial Defect. Biomaterials 2015, 37,
218−229.
(64) Bertaux, E.; Le Marec, E.; Crespy, D.; Rossi, R.; Hegemann, D.
Effects of Siloxane Plasma Coating on the Frictional Properties of
Polyester and Polyamide Fabrics. Surf. Coat. Technol. 2009, 204, 165−
171.
(65) Crespy, D.; Golosova, A.; Makhaeva, E.; Khokhlov, A. R.;
Fortunato, G.; Rossi, R. Synthesis and Characterization of Temper-
ature-Responsive Copolymers Based on N-Vinylcaprolactam and
Their Grafting on Fibres. Polym. Int. 2009, 58, 1326−1334.
(66) Popa, A. M.; Eckert, R.; Crespy, D.; Rupper, P.; Rossi, R. M. A
New Generation of Ultralight Thermochromic Indicators Based on
Temperature Induced Gas Release. J. Mater. Chem. 2011, 21, 17392−
17395.
(67) Agarwal, S.; Greiner, A. On the Way to Clean and Safe
Electrospinning-Green Electrospinning: Emulsion and Suspension
Electrospinning. Polym. Adv. Technol. 2011, 22, 372−378.
(68) Varesano, A.; Vineis, C.; Tonetti, C.; Ramirez, D. O. S.;
Mazzuchetti, G.; Ortelli, S.; Blosi, M.; Costa, A. L. Multifunctional
Hybrid Nanocomposite Nanofibers Produced by Colloid Electro-
spinning from Water Solutions. Curr. Nanosci. 2015, 11, 41−48.
(69) Friedemann, K.; Corrales, T.; Kappl, M.; Landfester, K.; Crespy,
D. Facile and Large-Scale Fabrication of Anisometric Particles from
Fibers Synthesized by Colloid-Electrospinning. Small 2012, 8, 144−
153.
(70) Wu, C. J.; Yuan, W.; Al-Deyab, S. S.; Zhang, K. Q. Tuning
Porous Silica Nanofibers by Colloid Electrospinning for Dye
Adsorption. Appl. Surf. Sci. 2014, 313, 389−395.

H DOI: 10.1021/acs.accounts.5b00524
Acc. Chem. Res. XXXX, XXX, XXX−XXX