Synthesis,Strategies,for,Polymer,Hollow,Particles

SHEN Xinyi，ZHANG Sen，WANG Shutao，3，SONG Yongyang*

（1.Chinese Academy of Sciences Key Laboratory of Bio-inspired Materials and Interfacial Science，Technical Institute of Physics and Chemistry，Chinese Academy of Sciences，Beijing 100190，China；
2.University of Chinese Academy of Sciences，Beijing 100049，China；
3.Qingdao Chinese Academy of Sciences Future Research Institute Co.，Ltd.，Qingdao 266109，China）

Abstract Polymer hollow particles have received much attention in the last two decades due to their unique structure and fascinating properties.They exhibit low density，large surface area，and high loading capacity properties，showing great promise in applications ranging from catalysts，drug delivery carriers，to energy storage.In this review，we summarize the synthesis strategies of polymer hollow particles，including templating synthesis，emulsion polymerization，self-assembly，microfluidics，and some other strategies.The synthesis principle，typical process，advantages，and disadvantages of these strategies have been elaborately illustrated and discussed.We also point out some challenges of existing strategies and some shortcomings of polymer hollow particles and provide an outlook on the future developments of the preparation and application of polymer hollow particles.We expect more strategies will be developed for the synthesis of polymer hollow particles with enhanced performance and multiple functions.

Keywords Polymer particle；
Hollow structure；
Template；
Emulsion polymerization；
Self-assembly

Polymer particles have received much attention in biomedical［1］，environmental［2］，food［3］，and many other fields.The properties of polymer particles are greatly influenced by their structures［4］.For example，porous particles can be used for molecule separation［5，6］，hollow particles can be used for cargo loading［7］，and Janus particles can be used for droplet stabilization［8］.Among them，hollow polymer particles exhibit many distinctive properties，including low density，high surface area，and large interior voids.These superiorities make them ideal candidates for the encapsulation of drug molecules and modification of functional nanoparticles.Hence，they are widely used in fields ranging from drug loading and release［9］，self-healing［10］，energy storage［11］，separation［12，13］，to microreactor［14，15］.However，conventional methods for the preparation of polymer particles，such as emulsion polymerization，suspension polymerization，and dispersion polymerization，always produce solid particles.It is still a challenge to prepare polymer hollow particles with these conventional methods.

In recent years，many strategies have been proposed for the preparation of polymer hollow particles［16，17］including templating synthesis，emulsion polymerization，self-assembly，microfluidics，and others.Templating strategy is the most frequently used approach to prepare polymer hollow particles［4］.A core as template materials is coated by desired polymer to form the shell，after the removal of templates，polymer hollow particles are obtained.However，the core-removal steps are complicated due to the use of acid，base，or organic solvent.In contrast，emulsion polymerization and self-assembly strategies can achieve the preparation of polymer capsules without post processing［16］.Microfluidic strategy has been widely used for the fabrication of microspheres.The size of polymer hollow spheres prepared by microfluidics are extremely uniform，and the thickness of the shell can be well tuned by regulating the flow rate［18］.However，to the best of our knowledge，most of the current reviews focus on the preparation of microspheres by the template strategy，and there are rare reviews that systematically summarize the synthesis strategies.Therefore，it is desirable to review the synthesis strategies of polymer hollow particles comprehensively.

In this review，we focus mainly on synthesis strategies of polymer hollow micro/nanoparticles，including the template strategy，emulsion polymerization strategy，self-assembly strategy，microfluidic strategy，and some others.Recent progress of the polymer hollow particles has been discussed in detail.Their principle，process，advantages，and disadvantages are also presented.Finally，some of the challenges and opportunities of the synthesis strategy for polymer hollow particles are proposed.

Template strategy has been widely used for the preparation of hollow particles，including polymer and inorganic particles.The principle of the template strategy involves constructing core/shell particles and removal of the core materials.The types of the template include hard particles，for example，SiO2and polystyrene（PS）spheres，and soft materials，for example，liquid droplets and air bubbles.In this part，we show some examples of polymer hollow particles synthesized by the hard temple strategy and soft template strategy.

2.1 Hard Template Strategy

Hard template strategy is conceptually the simplest method to synthesize hollow spheres.Generally，this strategy includes three steps：（1）preparation of the hard template particles；
（2）coating of the polymer layer；
（3）removal of the hard template particles.Rigid SiO2［19—21］and PS［11，22，23］micro/nanoparticles are the most frequently used hard template materials.The coating of polymer can be achieved by the polymerization of monomers or the assembly of polymers.The hard templates can be removed by dissolution，chemical etching，or thermolysis，depending on the properties of template materials.For example，poly（methacrylic acid）（PMAA）hollow microparticles were prepared by the hard template strategy using 3-（trimethoxysilyl）propylmethacrylate（MPS）modified SiO2as the template materials.First，MPS modified SiO2microparticles were prepared by the Stöber process.Then PMAA was coated on the microparticles after polymerization of MAA with 2，2′-azobis（2-methylpropionitrile）（AIBN）as initiator and ethylene glycoldimethacrylate（EGDMA）as cross-linker.At last，SiO2microparticles were removed by using HF as etching agent［Fig.1（A）and（B）］，resulting in PMAA hollow microparticles with shell thickness of 20 nm［24］.PS can also be used as hard templates for the preparation of poly（acrylamide-ethylene glycol dimethacrylate）［P（AA-EGDMA）］hollow microparticles［25］.P（AA-EGDMA）was coated on PS after polymerization.Then PS was dissolved by tetrahydrofuran，resulting in P（AA-EGDMA）hollow particles with a hole on the surface.

Fig.1 Hard template strategy for the synthesis of polymer hollow microparticles

Except for polymerization of monomers，layer-by-layer（LBL）assembly of polymers on the surface of templates is another approach to achieve polymer coating and subsequently to prepare polymer hollow particles.The LBL assembly refers to sequential deposition of different polymer species on the template particles mediated by intermolecular interactions.The shell thickness and multilayer structure can be well controlled by the assembly cycles.For example，poly（methyl methacrylate）（PMMA）stereocomplex microspheres were prepared by the alternate LBL assembly of it-and st-PMMA on silica nanoparticles［26］.After ten cycles of deposition，ten double layers of it-and st-PMMA were coated on the surface of SiO2.After removal of the template by HF，uniform PMMA hollow particles with a shell thickness of 90 nm were obtained［Fig.1（C）］.

Reproducibility and mono-dispersibility are the main advantages of using solid particles as template.However，harsh chemical reagents（e.g.，acids，organic solvents）are required to dissolve the employed template materials，which may destroy the functional groups on the surface of particles［27］.

2.2 Soft Template Strategy

Without using harsh chemical reagents to remove the hard template materials，soft template strategy has emerged as an alternative template strategy for the synthesis of polymer hollow particles.At first，emulsion droplets［28］and air bubbles［29］are prepared by an emulsification process and a sonication process，respectively.Size of emulsion droplets and air bubbles usually ranges from 10 nm to 100 μm.After polymerization of monomers or assembly of polymers，polymer hollow particles with adjustable thickness can be obtained.Compared with hard templates，the soft templates can be removed by washing and drying conveniently and eco-friendly.

Hollow poly（o-methoxyaniline）microparticles with a hole on the surface can be prepared by emulsionbased soft template strategy［Fig.2（A）］［30］.O-methoxyaniline droplets were dispersed in aqueous solution of ammonium persulfate（APS）.And the polymerization took place at the water/droplet interfaces due to the hydrophilicity of APS，which resulted in the formation of original hollow nanospheres.Followed by the aggregation and fusion process，such hollow nanospheres transformed into micro-sized hollow spheres.With the consumption of monomers in the outer surface of hollow spheres，monomers diffused from the droplets to the external surface to continue the polymerization reaction.After being washed with deionized water and dried，hollow spheres were obtained.

Fig.2 Soft template strategy for the synthesis of polymer hollow particles

Due to the thermodynamical instability of emulsion，surfactants are necessary to reduce the interfacial tension between the dispersed phase and the continuous phase.However，removal of surfactants from products is not easy［31］.Pickering emulsion，stabilized by nanoparticles，emerged as molecular surfactant-free emulsions.Pickering emulsion templated interfacial atom transfer radical polymerization（PETI-ATRP）was reported to prepare microcapsules［Fig.2（B）］［32］.Cationic LUDOX（CL）nanoparticles were coated electrostatically with poly［sodium styrene sulfonate-co-2-（2-bromoisobutyryloxy）ethyl methacrylate］（PSB），an anionic initiator for ATRP.The obtained PSB-modified CL particles were surface active and could be used to stabilize oil-in-water（O/W）Pickering emulsions.Since the initiator was coated on CL particles，the hydrophilic and hydrophobic monomers were confined to polymerize at the O/W emulsion interface，producing a shell layer of hollow microspheres by ATRP.Finally，particles were purified by simple washing and evaporation.Since the shell of polymer hollow particles contained nanoparticles，their mechanical properties were greatly improved.

Colloidosomes are hollow particles whose external shell is composed of colloidal particles［33］.In emulsion system，colloidal particles self-assemble on the surface of droplets according to the interaction determined by their own nature and surface properties［34］.Therefore，the function of colloidal particles is to stabilize the emulsion droplets which act as soft templates.PS hollow particles with precise control of size，permeability，mechanical strength，and compatibility were prepared by the self-assembly of nanoscale PS particles［Fig.2（C）］［35］.First，PS nanoparticles spontaneously adsorbed on the interface of O/W emulsion droplets to reduce their surface energy.Then，the adsorbed particles were lightly sintered to make them locked together.After sintering，particles with elastic shells and uniform holes were formed.Finally，the particles were transferred to water by gentle centrifugation to exchange the fluid inside the particles with the external one，which ensured that there was no surface tension between the internal and external fluids and the permeability of the shell was controlled by the interstitial holes.Besides，crosslinked polymersomes can also be used as colloidal nanoparticles to fabricate polymer hollow particles［36］.In the first step，block poly（ethylene glycol）-b-poly（styrene-co-3-isopropenyl-a，a-dimethylbenzylisocyanate）formed crosslinked micellar structures in the mixture of water and tetrahydrofuran.Then，crosslinker was added in the mixture to prepare crosslinked polymersomes.Homogenizing the water and organic solvents in the presence of polymersomes resulted in emulsion droplets，which were stabilized by the crosslinked polymersomes.After subsequent processing，polymer hollow particles were obtained，whose shells were composed of crosslinked polymersomes.

In addition to emulsion droplets，air bubbles are also commonly used as soft templates.For example，polyelectrolyte hollow particles are obtained by stepwise LBL deposition of oppositely charged polyelectrolytes onto the“air”core［Fig.2（D）］［29］.First，an air microdispersion in water was formed by ultrasound generator.Then，positively charged poly（allylamine hydrochloride）（PAH）and negatively charged poly（styrene sulfonate）（PSS）layers were adsorbed in alternation.After several repetitions，hollow capsules were obtained.The resulting capsules with entrapped air are less dense than water and can be collected easily at the top of the vial upon centrifugation at low rotation speed（＜500 r/min）or by“reverse”sedimentation.

The template strategy is a versatile and general approach to prepare polymer capsules with pores in the shells，allowing the morphology，size，composition，and other properties of the capsules to be finely tuned［37］.However，it may not be desirable in the manufacturing process since the removal process of hard templates using strong alkalis，hydrofluoric acid or organic solvents makes the synthesis process complex and requires an extremely thorough cleaning step.In addition，the droplets and bubbles used as soft templates are not easily to be controlled in consideration of stability and morphology.Therefore，it remains a great challenge to develop more convenient and template-free strategies to prepare polymer hollow particles.

Emulsion polymerization is a classical approach to prepare polymer microspheres.In traditional emulsion polymerization system，monomers are dissolved in the dispersed phase，and solid polymer microspheres are always resultant after polymerization.Polymer hollow particles can be prepared by introducing seed polymer into the emulsion droplets with initiator dissolved in the continuous phase.In the process of polymerization，phase separation occurs due to the incompatibility between the seed polymer and the newly-formed cross-linked polymer，which leads to the formation of a void inside the particles.Interfacial polymerization is another strategy to fabricate polymer hollow particles by confining the polymerization at the interface of droplets.In this strategy，water-in-oil（W/O）emulsion or O/W emulsion is prepared first with water-soluble monomers and oil-soluble monomers dissolved in water phase and oil phase，respectively，and initiator is dissolved in the dispersed phase.After the reaction is initiated，monomers aggregate and polymerize at the interface of emulsion droplets，forming the shell of hollow particles.

3.1 Seed Polymerization

Polymer hollow particles can be fabricated by seed polymerization.Polymer beads are first swelled by monomer droplets，and then phase separation occurs after polymerization，resulting in a hollow structure［38，39］.For example，P（St-MMA-MAA）copolymer latex particles were used as seeds to prepare monodisperse polymer hollow spheres［40］.P（St-MMA-MAA）seeds were first swollen by oil droplets containing MMA，divinyl benzene（DVB），and 2-hydroxyethyl methacrylate（HEMA），with potassium persulfate（KPS）as initiator in water phase.Polymer shell was first formed at the surface of O/W emulsion surface and the seed polymer gradually moved from center to the shell with monomers，forming a void on the shell due to osmotic pressure［Fig.3（A）］.Highly charged hollow latex particles were prepared by seed polymerization using poly（styrene-co-acrylic acid）［P（St/AA）］as seeds and methyl methacrylate（MMA），DVB，acrylic acid（AA）as monomers［41］.First，MMA and DVB in the oil droplets swelled P（St/AA）seed，and AA was dissolved in water phase.After the polymerization was initiated by KPS，hollow structure was formed gradually due to the phase separation between P（St/AA）seed and P（DVB/MMA/AA）crosslinked shell.

Fig.3 Emulsion polymerization strategy for the synthesis of polymer hollow particles

3.2 Interfacial Polymerization

For the synthesis of polymer hollow microspheres，interfacial polymerization refers to polymerization and cross-linking which can only occur at the O/W emulsion interface，resulting in polymers serving as hollow sphere shells.This approach is also much less dependent on the properties of monomers，making it possible to encapsulate a wide range of materials and to design functional polymer hollow particles by taking advantage of the diversity of vinyl monomers available.

Scottet al.［42］reported the interfacial free-radical alternating copolymerization for the first time，which allowed precise control of the onset of reaction，leading to the direct encapsulation of submicrometer liquid drops within nanometer-thick polymer shells.This approach is a radical copolymerization between hydrophobic maleates and hydrophilic vinyl ether monomers，which is initiated by a surface-active initiator that produces radicals at the oil-water interface.As described in Fig.3（B），interfacial radical polymerization of microemulsion oil droplets（Ⅰ）was initiated at the oil/water interface by the surface-active initiator（3）.Polymer capsules（Ⅱ）were formedviaalternating copolymerization of dibutyl maleate（1）and hydrophilic polyethylene glycol（PEG）divinyl ether（2）.Unlike other interfacial polymerization，where the polymers“grow”from the surface，this method allows the uniform growth of polymers from the inside.In another system，hollow-structured Poly（N-isopropylacrylamide）（PNIPAM）microspheres were prepared by one-pot interfacial polymerization approach at the interface of inverse W/O emulsion，whereN-isopropylacrylamide（NIPAM）monomer was first dissolved in aqueous phase and toluene was used as oil phase［43］.A redox initiation system containing benzoyl peroxidein oil phase and tetraethylenepentamine in water phase was used to conduct polymerization at the oil/water interface.As the polymerization continues，cross-linked PNIPAM network was formed at the interface with a hollow microsphere structure.Besides，hollow microspheres of polyaniline（PANI）were fabricated by interfacial polymerization with organic acid acting as surfactant and dopants［44］.In the presence of excess aniline，due to the basic and hydrophobic property of aniline monomers，vesicles with a shell of organic acid/anilinium salt were formed.Because the initiator（APS）is water-soluble，the polymerization proceeds on the surfaces of the droplets，producing PANI hollow particles.

3.3 Supramolecular Emulsion Interfacial Polymerization

Supramolecular hollow nanospheres can be fabricated by the method of supramolecular emulsion interfacial polymerization［Fig.3（C）］［45］.The water-soluble monomerN，N′-bis［1-（N-maleimido）-3-propyl］-N，N，N′，N′-tetramethyldodecane-1，12-diaminium（MA-C12）acted as both building block and surfactant，and the oil-soluble supramonomer 2-（mercaptoethyl-ureido）-pyrimidinone derivative dimer［（UPy-SH）2］endowed the forming of nanospheres.They encountered and reacted at the interface of the O/W emulsion droplets formed by ultrasonication.Due to the amphiphilicity of supramolecular polymers，they rapidly aggregated into nanospheresin situ，fabricating stable nanospheres by self-assembly.After interfacial polymerization of supramonomers and monomers，supramolecular hollow nanospheres were obtained.

These polymer hollow particles fabricatedviaemulsion polymerization demonstrate uniform shell thickness because the polymerization is confined to the isotropic emulsion interface［46］and the initiation can be precisely controlled［42］，providing a uniform and stable interface for polymerization.In addition，both interfacial radical polymerization and seed polymerization are one-step strategy to synthesize polymer hollow microparticles，without the complicated removal of cores by dissolving or drying the particles.

The self-assembly strategy provides a versatile method for preparing polymer hollow particles［31，47］.Typically，amphiphilic molecules form vesicles，which serve as the source of polymer framework for hollow particles by spontaneous interfacial aggregation and alignment.In this part，we show some examples of polymer hollow particles synthesized by the self-assembly strategy.

Star-shaped poly（L-lactic acid）（SS-PLLA）nanofibrous hollow microspheres were fabricated by selfassembly［48］.First，SS-PLLA was synthesized by using poly（amidoamine）（PAMAM）dendrimers as initiators.Then，the resultant star-shaped polymers were dissolved in tetrahydrofuran and emulsified into liquid microspheres，where SS-PLLA was used as building blocks to assemble SS-PLLA microspheres by a surfactant-free emulsification process.At last，the mixture was quenched in liquid nitrogen to induce phase separation，forming nanofibrous hollow microspheres after solvent extraction［Fig.4（A）］.

Self-assembly of block copolymers is a versatile strategy for controllable preparation of a broad range of functional materials with different ordered structures［49］.Self-assembly of amphiphilic block copolymers allows the spontaneous formation of vesicles in selective solvents，leading to the formation of hollow microspheres.A-B linear diblock copolymer，such as poly（ethylene oxide）-b-poly［3-（trimethoxysilyl）propyl methacrylate］（PEO-b-PTMSPMA）［Fig.4（B）］，was reported to synthesize polymer hollow particles.The vesicles were prepared first by self-assembly of the block copolymer in a selective solvent，then the PTMSPMA block was subjected to hydrolysis and polycondensation reaction to fix vesicle wall in the presence of triethylamine as a catalyst［50］.In addition，hollow nanoparticles were prepared by amphiphilic ABA-triblock copolymer，poly（2-methyloxazoline）-b-poly（dimethylsiloxane）-b-poly（2-methyloxazoline）［（PMOXA-PDMS-PMOXA）］［Fig.4（C）］，which carries polymerizable groups at both ends［51］.The polymer aggregated spontaneously in dilute aqueous solution into vesicular structures，the size of which can be controlled in the range from 50 to 500 nm［52］.These aggregations can be considerably stabilized by a subsequent crosslinking polymerization of the reactive end groups of the underlying triblock copolymers.

Fig.4 Self-assembly strategy for the synthesis of polymer hollow particles

As described above，self-assembly occurs in a hybrid system，which requires extra purification procedures to remove the solvents，such as dialysis.And vesicles formed by self-assembly are sensitive to environment conditions in many cases，which usually leads to collapse of polymer hollow particles during the drying process.In addition，it is difficult to accurately control the size distribution of particles，especially in largescale production［53］.

Due to the precise controllability and operating stability［54］，microfluidic technology has demonstrated significant advantages in producing monodispersed bubbles［55，56］，droplets［57，58］and multiple emulsions with controlled structures over previous methods［59—61］.Nano/microdroplets containing gas，single or multiphase liquid with uniform and controllable size are produced through microfluidic device by regulating the fluid shear force.After polymerization of monomers inside the droplets，polymer hollow particles are obtained.

Based on gas-liquid（G/L）emulsions and liquid-liquid（L/L）emulsions，gas-liquid-liquid emulsions have gained increasing attention from researchers due to their novel structure and low density［54］.Moreover，encapsulating gas as the inner phase forming gas-in-oil-in-water（G/O/W）double emulsions is an effective strategy to prepare hollow microspheres.G/O/W emulsions，prepared by capillary microfluidic device，have been proposed for the preparation of hollow microspheres with thin polymer shells［62］.Gas was injected in water phase through the smaller capillary with middle oil phase（containing photo-initiator），forming monodispersed G/O/W emulsion droplets，which were exposed to UV irradiation as soon as they flowed out of the channel［Fig.5（A）］.The polymerization reaction was initiated and the whole solidification process was fast enough to form solid shells ensuring the encapsulation of the microbubbles.A relative wide range of shell thickness from several microns to tens of microns can be easily adjusted by tuning the flow rates of the middle and outer phases.

Fig.5 Microfluidic strategy for the synthesis of polymer hollow microspheres

Poly（dimethylsiloxane）（PDMS）microfluidics have been widely demonstrated to produce microparticles by solvent extraction and evaporation methods［63］.Monodisperse hollow microparticles composed of three different polymers were prepared by using a PDMS based microfluidic device［64］.Acetylated dextran（Ac-Dex），hypromellose acetate succinate（HPMC-AS），and poly（lactic-co-glycolic acid）（PLGA）polymers dissolved in dimethyl carbonate（DMC，oil phase）were used for preparation of monodisperse O/W droplets in the PDMS microdevice.Initially，the polymer concentration in the droplet was uniform，and solvent diffusion through the oil-water interface led to droplet shrinkage，polymer accumulation and solidification at the oil-water interface，together with slow phase separation within the inner part of the particle.This process eventually culminated in the breakup of the outer shell and the release of the inner solvent through the hole.However，when the polymer concentration was low，phase separation would occur before the polymer formed a solid shell，which led to premature solvent release，forming a dimple on the particle surface［Fig.5（B）］.

In comparison with conventional emulsification techniques，microfluidics is also advantageous in terms of fabricating double emulsions，which enables the formation of polymer hollow particles with thick shells［65］.For example，mechanically robust microcapsules exhibiting a porous shell structure with controlled permeability were fabricated by microfluidics［66］.Water-in-oil-in-water（W/O/W）double emulsions were made in a glass capillary microfluidic device as templates for the formation of capsules with a UV-curable mixture of monomers in oil phase.The double emulsions can be converted into monodisperse microcapsules with macroporous shells upon UV polymerization-induced phase separation［Fig.5（C）］.The porous shell consists of a network of interconnected polymer particles that are formed upon phase separation within the oil phase of the double emulsion，and the shell thickness can be tuned by varying the inner and middle flow rates［18，65］.

Producing extremely uniform microspheres of specific size is the main advantage of microfluidic technology over the conventional strategies mentioned above.However，the cost of fabricating microfluidic device is much higher，the throughput remains to be improved，and it is still a challenge to prepare polymer hollow microparticles with smaller size using microfluidics.

Most of the conventional synthesis strategies require pre-organized structures or templates to construct the polymer hollow particles，and some of them require precise equipment.In addition，multi-step post processes including template removal，repeated centrifugation or filtration，or separation of large amounts of surfactant are required.Therefore，there is an urgent demand to develop new synthetic methods and to find molecules with unique structural properties for the simple preparation of polymeric hollow microspheres.

6.1 Freezing

Freezing is a unique strategy to synthesize polymer hollow particles.This method does not involve precisely regulated synthesis and subsequent complex processing，and only requires quenching and phase separation to obtain hollow structures.For example，microporous polymer shells with controllable holes was prepared by freezing strategy［67］.Monodisperse PS nanospheres were first dispersed in water and then swollen by toluene（a good solvent of PS）with the polymer bead radius expanding.After pouring the aqueous suspension into liquid nitrogen（Melting point：-210 ℃），both the solvent and water were quickly frozen.After solidification，toluene and the polymer moved towards the surface，creating a hole at the center.Finally，the sample was kept in a freeze-dryer and slowly warmed up to make the toluene evaporate.In this process，when the temperature reached the melting point of toluene（-93 ℃），the void size increased since PS chains can move towards the particle surface driven by the flux of evaporating toluene［Fig.6（A）］.Although the freezing strategy avoids complex synthesis and post processing，it leads to non-uniform size and poor tunability.Besides，the entire evaporation process must be carried out below 0 ℃to preserve the porous hollow structure，which may limit their large-scale preparation.

Fig.6 Other strategies for the synthesis of hollow polymer particles

6.2 Direct Synthesis

Monomer with a flat core and multiple polymerizable groups at the periphery directly can be used for the preparation of polymer nanocapsules with a highly stable structure without any preorganized structure，emulsifier，or template.For example，（allyloxy）12cucurbit［6］uril（rigid disk-shaped molecule with cavity）and dithiol polymerized into polymer nanocapsules spontaneously［68］.In the initial stage of the reaction，the disk-shaped monomers formed dimers and trimers linked by thioether linkages，which further reacted with each other to grow into two-dimensional（2D）oligomeric patches.As the reaction proceeded，the 2D oligomeric patches with a certain size started to bend to reduce total energy，generating a loosely cross-linked hollow sphere［Fig.6（B）］.This mechanism is similar to that of the formation of vesicles and virus selfassembly［69，70］.In addition，the polymer shell comprising a host molecule，allows facile tailoring of its surface properties in a noncovalent and modular manner by virtue of the unique recognition properties of the accessible molecular cavities exposed on the surface.The direct synthesis strategy has been demonstrated without using any preorganized structure，emulsifier，or template，but it is applicable for limited monomers with a flat core and multiple polymerizable groups at the periphery.Direct synthesis of hollow particles needs precise synthesis condition，and the effects of various factors such as monomer concentration，reaction temperature，and medium on the formation of polymer nanoparticles are rather complicated.In addition，direct synthesis of hollow particles can only produce nanoscale particles and the requirement of synthesis condition is relatively high，so this method is greatly limited due to high cost and complicated preparation process.

6.3 Coordination Polymer One-pot Solvothermal Reaction

Porous coordination polymers are highly ordered porous materials that connect metal ions or metal oxide clusters to multidentate organic ligands without any additional templates［71—73］.It is a promising approach to design hollow microspheres by constructing shells of hollow materials with porous coordination polymers.Hollow coordination polymer microspheres with microporous shells were formed by a one-pot solvothermal reaction，where the shells are constructed of iron-based ferrocenyl coordination polymers［74］.Large number of small coordination polymer crystallites congregated to large solid spheres，and the external crystals grow gradually while the internal crystals dissolve and migrate to the surface，forming cavities inside the spheres［Fig.6（C）］.At the same time，the crystallization of the coordination polymer makes the shell of the hollow microspheres microporous.The tunable and functional nature of the coordination polymers makes it easy to control the size of the microporosity within the shell and the functionality of the framework by selecting different metal ions or ligands，or by subsequently modifying the framework with functional groups.The coordination polymer one-pot solvothermal reaction strategy is suitable to produce relatively large hollow structures，mostly in the micrometer or sub-micrometer range，it remains a challenge to extend this method to prepare nanoscale particles.

Over the past two decades，polymer hollow particles have received increasing research interest due to their distinctive properties and widespread applications.In this review，we have summarized the principle，process，advantages，and disadvantages of existing synthesis strategies for polymer hollow particles.The template strategy requires the preparation of spherical frameworks first，followed by coating desired materials at the surface of templates，and then polymer hollow particles are obtained after removing the templates.The hard template strategy refers to rigid polymer or inorganic particles as the templates，which is a relatively straightforward approach and is suitable for the preparation of many types of hollow polymer particles，hence it is considered as the most popular strategy.Nevertheless，this approach suffers from tedious multi-step procedures for removing the template particles and the utilization of corrosive agents，which potentially impedes the massive production of polymer hollow particles.In contrast，the soft templates including emulsion droplets and air bubbles can be easily removed by common solvents or can be pyrolyzed at high temperature under inert atmosphere.Alternatively，emulsion polymerization and self-assembly are one-step strategies to fabricate polymer hollow particles without using templates.By restricting the polymerization at the emulsion interface，polymer hollow particles with uniform shell thickness can be obtained by emulsion polymerization strategy.Although both soft template strategy and emulsion polymerization strategy are proceeded in the emulsion system，there are some differences.Soft template，such as air bubbles and liquid droplets，only works as frameworks.Monomers polymerize on the surface of templates，while air and liquid in the emulsion droplets don’t participate in the polymerization.In addition，the template often needs to be removed after polymerization process.In contrast，in the emulsion polymerization strategy，monomers are included in the droplets，and they polymerize to the shells of the polymer hollow particles.The polymerization starts at the interface of emulsion droplets，and the hollow core is formed as the monomers are consumed.Therefore，polymer hollow particles can be prepared by a one-step process without removing templates.Amphiphilic molecules，such as block copolymers，form vesicles by self-assembly in the solution，and polymer hollow particles are fabricated after non-covalent packing of vesicles.However，vesicles formed by self-assembly are easy to collapse during the drying process，and it is difficult to precisely control the emulsion droplet size.The microfluidic strategy emerges as an effective approach to prepare droplets with controllable and uniform size by regulating fluid shear force.Additionally，the shell thickness of the hollow polymer particles can be well controlled by regulating the flow rate.However，the microfluidic strategy encounter bottlenecks including throughput，device stability，economic issues，and relatively large size.

Although great progress has been made in the synthesis of polymer hollow particles，there are still some problems and challenges.First，polymer hollow particles exhibit a relatively low mechanical robustness compared with inorganic materials，they are prone to collapse in practical applications.Although their mechanical property can be improved by anchoring nanoparticlesviathe Pickering emulsion approach［75］，the solidity of the microsphere shell still needs to be improved.Second，most of the existing polymer hollow microspheres exhibit smooth surface or porous surface，it is still a challenge to achieve the regulation of surface nanostructures，which is very important for their interaction with biomolecules or biological particles in separation and detection applications［76，77］.Third，most existing strategies cannot simultaneously afford the requirements of huge production，uniformity，stability，and economy in industry.Therefore，it is necessary to develop nextgeneration synthesis strategies for the preparation of polymer hollow particles with enhanced performance in a large-scale and economic way［78］.

Future research on hollow micro/nanostructures should focus on synthesis methods and applications.From the synthetic view，it is necessary to prepare polymer hollow microspheres with varied surface nanostructures and multiple components，which can fulfill various applications in complex systems［76］.In addition，although selective modifications have been achieved on the inner and outer surfaces of several polymer hollow particles，it is still difficult to simultaneously integrate opposite property within polymer hollow particles，such as hydrophilicity/hydrophobicity，positive/negative charge，etc.From the application view，although many polymer nano/microspheres with hollow structures have been developed，their application fields remain to be expanded.Moreover，most of the polymer hollow particles are currently used forin vitroexperiments，however，theirin vivoefficacy still needs to be verified.Therefore，we expect more strategies will be developed for the synthesis of polymer hollow particles，especially with enhanced performance and multiple functions.

推荐访问:Strategies Synthesis Polymer