SiO₂micro-and nano-particles have many advantages,such as easy preparation,controllable pore structure,good monodispersity and uniform size,so they are widely used in template preparation of microcapsule materials.For example,Caruso et al.Prepared polydopamine microcapsules using SiO₂particles with diameters of 0.5,1,3,and 5μm as templates,respectively^[15]。 Polydopamine films were formed on SiO₂particles by oxidative self-polymerization deposition of dopamine in Tris-buffered solution at pH 8.5.Hydrofluoric acid was further used to remove the SiO₂nuclei to obtain monodisperse polydopamine microcapsules with uniform size.The size of the capsule and the thickness of the shell can be controlled by changing the particle size of the SiO₂and the polymerization time,respectively.In the above study,corrosive hydrofluoric acid was used to remove the SiO₂template.Therefore,Yang et al.Controlled the diameter of the SiO₂microspheres by changing the ratio of ethanol/water and the concentration of silicon alkoxide.The polydopamine shell was deposited on the surface of the carbon capsules and carbonized,and the template was removed by ammonia under hydrothermal reaction,and finally the hollow carbon capsules with more uniform size were obtained by a milder nucleation method^[16]。 Further,Nador et al.Coated dopamine on SiO₂mesoporous nanoparticles by ammonia-initiated oxidative self-polymerization^[17]。 The SiO₂template can be removed by dispersing the polydopamine-coated SiO₂in water without using any harsh chemical reagent,thereby preparing the polydopamine microcapsule.Similar to this work,Yu et al.Achieved the removal of the template core of SiO₂through a polydopamine-mediated water dissolution process^[18]。 The removal time of template core depends on the thickness of polydopamine shell,the calcination time of SiO₂and the ratio of water to SiO₂capsule.The results show that the polydopamine microcapsules obtained by this method can effectively retain the catalytic decomposition of hydrogen peroxide by catalase,which has guiding significance for the preparation of green and friendly hollow microcapsules 。

SiO₂or polystyrene(PS)particles are commonly used as hard templates to prepare microcapsules.Corrosive and toxic chemical reagents such as hydrofluoric acid or tetrahydrofuran are usually used to remove the nucleus of these two templates,which are easy to remain in the microcapsules and bring pollution and toxicity^[19]。 Therefore,the researchers further developed the preparation method of microcapsules using CaCO₃,MnCO₃particles as templates,both of which can be dissolved and nucleated using a mild aqueous solution of disodium EDTA.Shi et al.Prepared three kinds of CaCO₃microspheres：PAH-CaCO₃（(polyallylamine hydrochloride doped CaCO₃microspheres),Pure CaCO₃,PSS-CaCO₃（sodium polybenzenesulfonate doped CaCO₃microspheres),Polydopamine-coated CaCO₃core-shell structures were obtained by immersing the above templates in dopamine Tris buffer solution(pH=8.5),respectively.Three types of polydopamine microcapsules were prepared by further dispersing them in EDTA solution to remove the CaCO₃template^[20]。 Studies have shown that the higher the porosity and interconnectivity of the capsule wall,the higher the mass transfer coefficient.As a support for CAT immobilization,these enzyme-entrapped polydopamine microcapsules exhibited obvious structure-related activities。

In our group,polydopamine microcapsules were prepared by a one-step deposition method using soluble MnCO₃particles as templates^[21]。 Polydopamine microcapsules were prepared by dispersing dopamine monomer in Tris-HCl buffer solution containing MnCO₃particles for 12 H,and then removing the MnCO₃particles with EDTA.Furthermore,the morphology and shell thickness of the microcapsules were effectively adjusted by changing the concentration of dopamine and the pH value of Tris buffer solution.When the concentration of dopamine is low(1 mg/mL),the polydopamine shell is smooth and thick;When the concentration of dopamine is high(3 mg/mL),the polydopamine shell is wrinkled and thin.Moreover,the polydopamine shell was positively correlated with the pH of Tris-HCl buffer,and the thickness of the film increased with the increase of pH.In addition,dopamine can be directly deposited on the surface of insulin particles to achieve pH-responsive release of coated insulin(Fig.1),which is expected to be used for oral insulin administration in diabetic patients.Further in situ reduction of supported Ag nanoparticles on the surface of the microcapsules enabled efficient catalytic reduction of organic pollutants 4-nitrophenol and methylene blue^[22]。

hard templates have many advantages in the preparation of polydopamine microcapsules with uniform size.However,the nucleation process of hard templates mainly depends on harsh chemical reagents such as acids or organic solvents,which seriously limits the use of building blocks such as biomolecules.Compared with hard templates,soft templates(such as O/W emulsion droplets)can remove the template core by mild means such as extraction,evaporation and selective solvent dissolution,thus providing another effective strategy for the construction of polydopamine microcapsules.Caruso et al.Successfully prepared monodisperse polydopamine microcapsules with a size of 400 nm~2.4μm and a thickness of 10~30 nm in Tris buffer solution by controlling the droplet size of O/W emulsion by changing the concentration of dimethyldiethoxysilane(DMDES)^[23]。 Furthermore,functional substances,such as magnetic nanoparticles,quantum dots(QDs)and hydrophobic drugs,were pre-loaded in the emulsion droplets,and functional material-modified polydopamine microcapsules could be obtained after removing the DMDES emulsion template(Fig.2).in addition to using an emulsifier to construct an O/W emulsion system,Wang et al.Found that the O/W emulsion spontaneously enriched hydroxide ions at the two-phase interface,which not only stabilized the oil-water interface,It can also replace the Tris buffer solution to provide an alkaline environment for the oxidation of dopamine,so that polydopamine microcapsules with a diameter of 1.3-7.5μm can be prepared by O/W emulsion droplet method in sodium hydroxide(pH=8.2)solution^[24]。 Dopamine mainly polymerizes at the O/W interface.On the one hand,the surface pH of O/W droplets is much higher than that of the bulk aqueous phase,which makes dopamine preferentially polymerize at the surface of emulsion droplets;On the other hand,dopamine is deprotonated in the alkaline environment,the hydrophobicity is enhanced,the pK_aof dopamine amine group is lower than that at the interface,and the hydrophobic interaction between the oil phase and the deprotonated polydopamine chain contributes to the selective growth of polydopamine on the droplet surface.In addition,Jiang et al.Prepared poly(ethyl methacrylate)(PEMA)assemblies byγ-ray-induced liquid-liquid interfacial polymerization strategy(LLISA),further coated with polydopamine coating,and used ethanol to remove the template to obtain polydopamine microcapsules^[25]。 Compared with emulsion polymerization,the polymerization particles prepared by LLISA polymerization strategy have the characteristics of simplicity,high stability and no surfactant,and the polydopamine microcapsules prepared by LLISA polymerization strategy as a soft template can well retain the spherical structure and have excellent mechanical stability。

In addition to the use of O/W emulsion soft template,non-emulsion system can also be used as a soft template for the preparation of polymer microcapsules.Ni et al.Found that tetrahydrofuran and water are macroscopically homogeneously miscible,while tetrahydrofuran and Tris buffer solution can form heterogeneous domains of buffer droplets of 200~600 nm microscopically,which can be used as template cores for the formation of polydopamine microcapsules^[26]。 the structure of polydopamine microcapsules is highly dependent on the volume fraction of tetrahydrofuran,and regular microcapsules can be formed when the volume fraction of tetrahydrofuran is greater than 0.2.Furthermore,Amin et al.Used a mixture of dopamine and resveratrol(RV)in ethanol/water to prepare polydopamine microcapsules with a diameter of less than 200 nm^[27]。 hydrophobic stilbene resveratrol was used to induce the formation of capsules during the autooxidation of dopamine.A small portion of resveratrol reacted with oxidized dopamine to form soluble azamine fluorophores,and the rest of resveratrole was bound to polydopamine microcapsules through supramolecular interactions such as Hydrophobic interactions.Moreover,the diameter and wall thickness of the microcapsules can be controlled by changing the concentration of dopamine or the ratio of RV/DA。

Emulsion of 50~300 nm can be prepared by equal energy input of ultrasound.For example,Zhai et al.Used the anionic surfactant sodium dodecyl sulfate(SDS)to generate toluene microemulsion under the action of ultrasound,and dopamine was polymerized on the surface of toluene droplet template to generate polydopamine^[28]。 Microcapsules with a diameter of about 50 nm can be obtained by adjusting the concentration of dopamine,which provides a new and convenient method for the preparation of polydopamine microcapsules with a diameter of less than 100 nm.However,in the preparation of microemulsion using ultrasound,the high energy input of ultrasound may destroy the activity of sensitive substances in the capsule,for example,ultrasound can cause heating phenomenon as well as the formation of free radicals,which leads to the oxidation of sensitive materials,and it is difficult to control the size of soft templates such as emulsion droplets.To overcome these limitations,researchers employed Shirasu porous glass(SPG)membrane emulsification to produce highly monodisperse droplets under conditions of lower energy input.Zhai et al.Further explored the use of N₂pressure to push the oil phase(composed of toluene and hexadecane)through the SPG membrane into the aqueous phase containing surfactant SDS,prepared monodisperse emulsion droplets,and coated them with polydopamine coating by dopamine oxidative self-polymerization^[29]。 the pore size of SPG membrane can effectively adjust The size of emulsion droplets,so as to efficiently synthesize monodisperse polydopamine microcapsules with a diameter of 700 nm~2μm。

With the diversification of the application demand of polydopamine microcapsules,a single polydopamine material is difficult to meet various performance requirements.Polydopamine not only has universal adhesion properties,but also is rich in catechol and amino groups,which is conducive to the in-situ generation and loading of metal nanoparticles,as well as the modification of functional molecules through Schiff base reaction and Michael addition reaction,so as to realize the functional modification of polydopamine microcapsules.The catechol unit in polydopamine has strong reducibility,which can reduce noble metal ions in situ to form metal nanoparticles.For example,Tao et al.Used AgNO₃as a silver source to reduce Ag in situ on the surface of polydopamine microcapsules,and used Ag@PDA microcapsules not only to efficiently catalyze the degradation of organic compounds such as methylene blue,but also to show effective antibacterial properties against Escherichia coli and Staphylococcus aureus^[30]。 Similar to this work,Xi et al.Reduced Au in situ on the surface of polydopamine poly(lactic-acetic acid)microcapsules to obtain Au NPs@PDA/PLGA microcapsules,which can be used as an enhancer of ultrasound-guided high intensity focused ultrasound(HIFU)therapy,showing good in vitro ultrasound contrast imaging effect,and has broad application prospects in the clinical treatment of tumors^[31]。 In addition,polydopamine can be functionalized by Schiff base or Michael addition reaction with molecules containing amino or sulfhydryl groups.for example,Zhang et al.Used the Schiff base reaction between 1,3,5-triformylphloroglucinol,p-phenylenediamine and dopamine For dopamine polymerization and polycondensation to construct covalent organic frameworks(COFs)materials^[32]。 Reactive oxygen species(ROS)generated during the oxidative self-polymerization of dopamine can accelerate the nucleophilic reaction.Due to the inherent basicity of p-phenylenediamine,polydopamine-based Schiff base COFs can be synthesized in water/ethanol solutions at pH values greater than 8.Because the oxidative self-polymerization of dopamine is similar to the alkaline environment of Schiff base reaction,COFs can be connected in situ by the continuously generated polydopamine.the covalent interaction of dopamine with COFs and COFs ligands reduces the separation size of COFs membranes,and greatly improves the mechanical properties and stability of COFs membranes。

The polydopamine coating can also be used as an atom transfer radical polymerization(ATRP)platform to realize the surface functionalization of polydopamine microcapsules by grafting polymer brushes.Kohri et al.Used ATRP initiator to modify dopamine(dopamine reacted with isobutyl-2-bromine(BiBB)in situ)and dopamine oxidative copolymerization to realize the coating of polystyrene(PSt)microparticles and prepare PSt@PDA/BiBB_nparticles(n=0~3^[33]; [BiBB]/[DA],calculated from the molar concentrations of DA and BiBB).Hydroxyethyl methacrylate(HEMA)monomer was grafted onto the surface of microspheres by surface-initiated atom transfer radical polymerization(SI-ATRP),and then the template polystyrene particles were removed to prepare stable polydopamine microcapsules with controllable size and wall thickness.In the following work,Ma et al.Grafted 2-(2-methoxyethoxy)ethyl methacrylate-oligo(ethylene glycol methyl)acrylate polymer（P(ME₂OMA-co-OEGMA)）onto polydopamine-coated SiO₂microspheres by SI-ATRP,and prepared temperature-and pH-sensitive dual-responsive microcapsules after removing the SiO₂core,which showed high stability in different pH buffers(Fig.3)^[34]。

Polydopamine can also be co-deposited with non-ionic polymers(such as polyethylene glycol(PEG),polyvinylpyrrolidone(PVP),etc.)without covalent reaction.The co-deposition assembly of polydopamine and polymer is promoted by supramolecular interactions such as hydrogen bonding,π-πstacking,and cation-πinteractions,which provides a new way for the functional modification of polydopamine microcapsules.Zhu et al.Prepared CO₂isolated mixed matrix membranes(MMMs)with polydopamine/polyethylene glycol microcapsules as fillers^[35]。 Compared with polydopamine microcapsules without polyethylene glycol,the mesoporous structure of PDA-PEG microcapsules is beneficial to the rapid diffusion of gas into the lumen and reduces the transmembrane mass transfer resistance.The polyethylene glycol functional group not only increases the CO₂affinity of the capsule,but also avoids excessive chain rigidity at the polymer-filler interface.Due to the interfacial adhesion of dopamine,the long-term running stability of MMMs filled with PDA-PEG microcapsules at high temperature is significantly better than that of the commercially available Pebax film 。

the environmental conditions of high temperature or strong solvent may degrade the shell wall of the microcapsule,accelerate the diffusion of the core layer to the shell wall,and destroy the function of the polymer capsule.the preparation of new multilayer composite microcapsules is expected to solve this problem.For example,Kang et al.Prepared PU/UF double-layer core-shell microcapsules by polycondensation of urea-formaldehyde(UF)resin on the surface of PU microcapsules,and further coated the polydopamine shell to construct multilayer microcapsules^[36]。 The microcapsules exhibited low core loss at high temperature,about 10 wt%loss at 180°C for 2 H,and excellent thermal and solvent stability.The polydopamine coating can limit the diffusion of the core to the shell wall at high temperature,and in common organic solvents and alkaline aqueous solutions,the permeability of the microcapsule shell wall is lower,which can also serve as an effective barrier for core diffusion(Fig.4).Sun et al.Prepared a composite capsule（PDA(PAA-dopa/PVPON)_n）of dopamine-modified polyacrylic acid(PAA-dopa)and polyvinylpyrrolidone(PVPON )^[37]。 With the change of environmental pH,the hydrogen bonds in the PDA(PAA-dopa/PVPON)_ncomposite capsules were dissociated or reconstructed,showing a pH-responsive swelling-shrinking behavior.Capsules swell at high pH and shrink at low pH.Compared with the traditional layer-by-layer assembly technology,the introduction of polydopamine coating can save a lot of time required for the preparation of pH-responsive capsules.Essential oils(EOs)are volatile during processing and storage,and are highly susceptible to oxidative deterioration when exposed to oxygen,light,humidity,or heat.At present,most of the embedding strategies of EOs are layer-by-layer assembly or interfacial polymerization.However,layer-by-layer assembly methods have limited throughput and poor barrier properties,while interfacial polymerization often introduces non-biodegradable formaldehyde resin or unreacted reagents.Tian et al.Prepared nonionic surfactant-stabilized monodisperse EOs emulsion by membrane emulsification method,further deposited polydopamine coating on its surface,and prepared double-layer coacervated EOs capsules with gelatin-bound polydopamine coating as the in situ coacervation center of gum Arabic^[38]。 Compared with the traditional composite coacervate capsules,the polydopamine interlayer not only improves the sustained release performance of EOs under different release conditions,but also endows the capsules with excellent thermal stability.the novel bilayer structure achieved higher entrapment efficiency and drug loading,and prolonged the release time of EOs。

In addition to spherical polydopamine microcapsules,other types of particles,such as rods,squares,and elliptical templates,can also be used to construct abundant anisotropic polydopamine microcapsules.For example,Wang et al.Respectively used SiO₂microparticles,SiO₂@Au composite microparticles,SiO₂nanorods,a-Fe₂O₃@PDA yolk-shell particles,etc.As template particles to prepare polydopamine particles with various hollow structures,such as hollow spheres,ellipsoids,and yolk-shells,by oxidative self-polymerization of dopamine followed by hydrothermal treatment^[39]。 in this method,the coating and enucleation processes are carried out In the same medium without the use of complex instruments,and the process of removing template nuclei does not involve harmful chemicals.Moreover,through the selection of template particles or surface reactions,the particles can be adjusted from hollow structure to yolk-shell structure,and other hollow particles with complex structure and composition can be further prepared.Metal-organic frameworks(MOFs)are excellent template materials for the preparation of porous carbon and related functional materials due to their high specific surface area,abundant Lewis acid sites,intrapore availability,external surface functionalization,and good mechanical stability.Ye et al.Constructed MOF@PDA hybrid particles by coating the surface of MOF particles with polydopamine under alkaline conditions^[40]。 Due to the self-corrosion of the MOF template during the coating process,polydopamine microcapsules with the same morphology as the template can be produced.Due to the different activities of the crystal faces,the molecular sieve imidazolate framework-8(ZIF-8)with a truncated cubic shape is self-corroded to obtain a yolk-shell structure in the middle.This MOF@PDA nanoparticle is easily endocytosed by cancer cells,continuously releasing Zn²⁺in the cells to increase the concentration of metal ions,thus producing cytotoxicity in tumor HeLa cells to play an anti-cancer role.The unique metal ion chelating ability of polydopamine combined with the removable MOF template provides a facile method to prepare polydopamine microcapsules with anisotropy and different sizes under mild conditions.In addition,Zhou et al.Constructed polydopamine microcapsules by a one-step method using the competitive oxidation reaction of benzene-1,4-dithiol(BDT)and dopamine^[41]。 BDT first polymerizes on the surface of the template particle to form PBDT,and then dopamine polymerizes to obtain PDA,in which theπ-πstabilized PBDT core can be selectively dissociated in organic solvents to generate Polydopamine microcapsules.polydopamine microcapsules prepared by redox reaction can form complex yolk-shell nanostructures。

Improving drug loading rate and action efficiency is an important issue to be considered in drug delivery systems.Functionalized polydopamine microcapsules as drug delivery carriers can not only improve The efficiency of drug delivery and the targeted recognition of tumor tissues,but also reduce the marginal effect of drugs.Moreover,the construction of stimulus-responsive polydopamine microcapsules can improve the bioavailability of drugs and enhance the efficacy of drugs.the controlled release,targeted delivery and in vivo monitorable delivery of polydopamine microcapsules in drug delivery are described below。

Controlled release of drugs can not only improve the efficacy of drugs,but also reduce the toxic and side effects of drugs.Through the rational design of drug dosage form,the drug carrier can release the loaded drug molecules in response to the stimulation of in vivo signals such as pH,redox substances,enzyme concentration,etc.,or in vitro signals such as heat,light,electric field,magnetic field,etc.When the drug carrier changes from the neutral extracellular environment to the acidic environment of endosomes and lysosomes(pH=5~6),it will be affected by acidification,and the controlled release of drugs will be achieved through pH-triggered release strategy.This system is important for the intracellular delivery of drug molecules.Cui et al.Coupled the chemotherapeutic drug doxorubicin(Dox)with thio-poly(methacrylic acid)（PMA_SH）via a pH-cleavable hydrazine bond,and further,the thiol of the Dox-PMA_SHassembly reacted with the catechol of poly(dopamine),thereby immobilizing it onto poly(dopamine)microcapsules^[42]。 The drug-loaded Polydopamine microcapsule has good dispersibility and shows pH-responsive doxorubicin release property.Compared with free doxorubicin,polydopamine microcapsules loaded with doxorubicin had better killing effect on HeLa cells(fig.5).polydopamine microcapsules prepared by Yu et al.Exhibited excellent unidirectional permeability to rhodamine 6G(Rh6G)^[19]。 on the one hand,the loading of Rh6G increased with the increase of pH value,but the polydopamine microcapsules hardly absorbed Rh6G in ethanol solution.On the other hand,the loaded Rh6G can be released rapidly in ethanol,but slowly or not in buffer solutions with different pH values.Furthermore,Liu et al.Found that the absorption and release of small molecules by polydopamine microcapsules depend On the pH value of the solution^[43]。 the Zeta potential on the surface of polydopamine microcapsules is related to the pH of the solution.When the solution is at low pH,the polydopamine shell is positively charged due to the protonation of the amino group,which electrostatically interacts with the negatively charged methyl orange(MO)and alizarin red(AR),thus showing high loading.When the solution is at high pH value,the polydopamine shell is negatively charged due to the deprotonation of phenolic hydroxyl groups,and the electrostatic repulsion between MO and AR molecules and the polydopamine shell reduces the loading.However,the polydopamine shell has a strong electrostatic attraction to the cationic dye(Rh6G)molecules,and the drug loading increases with the increase of the pH value of the solution.Zong et al.Constructed pH-responsive liposome@PDA microcapsules,and found that the drug release rate of drug-loaded microcapsules increased with the decrease of solution pH^[44]。 in addition,5-fluorouracil(5-FU)-loaded liposome@PDA microcapsules exhibited better tumor cell killing efficacy than drug-loaded liposome capsules and free drug In natural tumor environment(pH 6.87)。

It is very important to select targeted molecular modification with good molecular recognition for targeted drug delivery.Among various targeting agents,folic acid,as a high-affinity ligand of folate receptor,has good targeting to brain,kidney,lung,breast and other cancer cells that highly express folate receptor.Cheng et al.Designed pH-responsive drug-loaded polydopamine microcapsules for cancer cells with folate receptor overexpression,which enhanced cancer cell toxicity through folate receptor-mediated endocytosis to achieve cell internalization^[45]。 Moreover,the drug-loaded microcapsules showed pH-responsive sustained drug release,which not only prevented premature drug release,but also limited drug release at non-targeting sites,so that the drug could be delivered to the targeting site to the maximum extent,thereby improving the bioavailability of the drug and maintaining the excellent biological activity of the drug molecule to induce cell death.Another common targeting ligand is molecularly imprinted polymer(MIP),also known as artificial receptor,which specifically recognizes the target molecule by matching its shape,size and functional group.Compared with the existing ligands,MIP has the advantages of high stability,low cost,easy preparation,and predictable structure.For example,in the presence of epidermal growth factor receptor(EGFR)template peptide,Liu et al.Used dopamine to undergo oxidative self-polymerization on the surface of ZIF-8@DOX particles,and then removed the template peptide by ultrasonication.At the same time,the catechol group of polydopamine and Zn²⁺corroded the ZIF-8 core through chelation,and drug-loaded molecularly imprinted polydopamine capsules(DOX@MIP)were obtained^[46]。 Studies have shown that DOX@MIP microcapsules are highly targeted to cancer cells with high expression of EGFR and can selectively kill cancer cells,but show low toxicity to normal cells.In addition,the chemical reactivity and photothermal conversion ability of polydopamine are beneficial for DOX@MIP microcapsules to achieve chemotherapy-photothermal therapy synergy。

by fluorescently labeling Polydopamine microcapsules,it is not only beneficial to monitor their safety and effectiveness as drug carriers,but also beneficial to achieve bioimaging and sensing.polydopamine is an excellent fluorescence quencher because it contains quinone groups generated By the oxidation of phenolic hydroxyl groups,which can capture excited electrons from fluorescent dyes under laser irradiation^[47]。 This also makes the fluorescent labeling of Polydopamine microcapsules very difficult.polydopamine microcapsules can be labeled using thiol-containing polymethacrylate-Alexa Fluor 488(AF488)dye conjugates,but the cross-linking process and conjugate labeling require multiple steps,significantly reducing the fluorescence labeling efficiency^[42]。 Therefore,Yu et al.Coprecipitated hemoglobin(Hb)and MnCO₃,and then used glutaraldehyde(GA)to crosslink and dissolve the MnCO₃template to obtain Hb microspheres.Further,dopamine was oxidized and self-polymerized on the Hb microspheres to prepare PDA-Hb microcapsules^[48]。 PDA and glutaraldehyde can be cross-linked to form a Schiff base bond,so there is no need to couple other fluorescent dyes,and the PDA-Hb microcapsules show autofluorescence properties originating from the n-π*transition of the Schiff base bond^[49]。 Dopamine can react with H₂O₂to form fluorescent small molecules doped into the polydopamine coating,which significantly enhances the fluorescence characteristics of polydopamine microcapsules.Chen et al.First prepared polydopamine microcapsules,and further utilized the reaction of dopamine and H₂O₂to construct fluorescent polydopamine microcapsules(F-PDA )^[50]。 the fluorescence of the microcapsule was related to the pH of the solution,and the order of fluorescence intensity from high to low was pH 3>pH 8>pH 4>pH 6>pH 7>pH 5,that is,the fluorescence intensity was the highest at pH 3.In addition,Quignard et al.Developed another method for the construction of autofluorescent polydopamine shells^[51]。 Dopamine is oxidized and self-polymerized on the surface of the oil droplet to form a polydopamine coating,and the polydopamine shell is photooxidized under ultraviolet irradiation to produce bright and lasting fluorescence.the results show that the intensity of fluorescence depends on the experimental parameters such as the wavelength of excitation light,the type of oil,and the polymerization conditions.Moreover,compared with the pure polydopamine coating,the polydopamine-coated O/W droplets can produce stronger fluorescence emission performance under ultraviolet irradiation,and can be applied to the fields of biological imaging,sensing and the like。

According to the world cancer Report 2020 released by the International Agency for Research on cancer(IARC)of the World health Organization,there were 19.29 million new cancer cases In the World in 2020,and more than 6,000 people died of cancer every day on average.cancer is a serious threat to human Health and family happiness.Although early detection of Cancer can prevent disease and effectively guide treatment,the development of effective and safe Cancer treatment methods remains a key issue.Common cancer treatments,such as chemotherapy,radiotherapy and surgery,have low targeting and serious side effects.Therefore,combination therapy strategies based on two or more treatments have attracted much attention because they are expected to overcome the disadvantages of monotherapy.in addition,the rapid development of nanotechnology provides a new opportunity for the efficient treatment of cancer,and the nanomedicine platform can form a series of targeted treatment programs from the aspects of early prevention,initial detection,accurate positioning,and direct administration of cancer^[52]。 However,because nano-drug delivery systems are often combined with functional molecules such as targeting agents and photosensitizers,which significantly increases the complexity of therapy,there is an urgent need to develop high-precision,efficient but simple multifunctional nano-drug carriers that integrate multiple therapeutic modalities in a single nanostructure to maximize synergistic effects.Based on these research backgrounds,the preparation of multifunctional nano-drug carriers with controllable size,morphology and surface properties by rationalizing and refining polydopamine microcapsules to load anticancer drugs has become a new research hotspot。

In tumor tissues,the local hypoxic microenvironment causes malignant biological behaviors such as proliferation and metastasis of tumor cells.Therefore,improving the hypoxic environment of tumors to improve the therapeutic effect is an effective target For cancer therapy.for example,Yu et al.Prepared PDA-Hb microcapsules by oxidative self-polymerization of dopamine on the surface of hemoglobin microspheres^[48]。 The cathodic current was measured by differential pulse voltammetry as an indicator of the oxygen carrying capacity of the microcapsules.It was found that after 30 s of oxygen adsorption,the peak current of PDA-Hb microcapsules and hemoglobin solution was 5.78 times and 3.45 times higher than the initial value,respectively,and the oxygen carrying effect of PDA-Hb microcapsules was more prominent.In addition,the PDA-Hb microcapsules were still able to release oxygen after immersion in N₂for 120 s.Moreover,PDA-Hb microcapsules can reversibly load and release oxygen.PDA-Hb also has good stability and biocompatibility,which can be used as an oxygen carrier in biomedical fields such as cancer therapy.Wu et al.Prepared oxygen-carrying microcapsules by oxidative self-polymerization of dopamine at the oxygen/water interface^[53]。 To demonstrate the ability of oxygen-loaded microcapsules to improve the hypoxic microenvironment,KPC cell lines were cultured in hypoxic environment（L-O₂group),normal oxygen environment（N-O₂group),and hypoxic environment with oxygen-loaded microcapsules（M-O₂group)(Fig.6A).KPC cells cultured in L-O₂environment were most in hypoxia state,and the fluorescence intensity labeled by hypoxia reagent was the highest,while the fluorescence intensity of KPC cells cultured in M-O₂environment was the lowest.The M-O₂environment had fewer KPC cells than the N-O₂environment,indicating that the oxygen-carrying microcapsule could be used as an excellent oxygen carrier compared with the normal oxygen environment,which could effectively improve the oxygen level and thus inhibit the proliferation of hypoxic cells(Fig.6 B,C).Furthermore,the tumor-bearing mice treated with oxygen microcapsules and gemcitabine(GEM)(M+G group)had the smallest tumor volume and weight(Fig.6 D,E),indicating that the synergistic treatment of oxygen microcapsules and GEM can effectively enhance the anti-tumor therapeutic effect 。

Due to the complexity of the tumor microenvironment and the heterogeneity of tumors,a single treatment strategy is difficult to effectively eliminate tumors because of its shortcomings such as poor drug resistance,inefficiency,and high toxicity.Therefore,a combination of two or more treatments is needed to overcome the limitations of a single treatment strategy.Common combination therapies include photothermal-chemotherapy,photothermal-chemotherapy-chemokinetic therapy,and photothermal-photodynamic therapy.Polydopamine nanomaterials have strong near-infrared absorption and high photothermal conversion efficiency,which can effectively kill cancer cells,inhibit tumor growth and not damage normal tissues^[54]。 polydopamine microcapsules can realize the synergistic treatment of photothermal therapy and chemotherapy by loading chemotherapeutic drugs.For example,Ding et al.Used amphiphilic copolymers to construct nanoparticles with core layer structure,and loaded two chemotherapeutic drugs,doxorubicin and paclitaxel,into the hydrophilic core layer and hydrophobic shell(NP-DT)of the nanoparticles,respectively.the siRNA was adsorbed onto the surface of the nanoparticles by electrostatic interaction(NP-DTS).Finally,the composite nanomedicine system was prepared by coating the drug-loaded nanoparticles with Polydopamine(NP-DTS-PDA)^[55]。 Polydopamine can not only effectively protect the leakage of chemotherapeutic drugs and improve the biocompatibility of nanomaterials,but also play the role of photothermal agents.When near-infrared laser is used to irradiate the tumor site,the polydopamine coating can not only generate enough heat for photothermal therapy,but also achieve thermosensitive drug release during chemotherapy and gene therapy,so that triple-negative breast cancer can be regressed.The polydopamine-shell modified composite material realizes the synergistic treatment of photothermal therapy,chemotherapy and gene therapy,and provides a new strategy for building a combined treatment system and improving the treatment effect of cancer.In addition,polydopamine can also be coupled with other photothermal agents,including gold nanoparticles,reduced graphene oxide,Prussian blue,etc.,and loaded with chemotherapeutic drugs to achieve the synergistic treatment of photothermal therapy and chemotherapy.For example,Xiang et al.Used Au nanorods,2-methylimidazole,and Zn²⁺to form a ZIF-8 intermediate,and induced the decomposition of ZIF-8 and the polymerization of dopamine through the difference of the coordination ability of 2-methylimidazole and ZIF-8 to Zn²⁺to obtain gold nanorod-loaded polydopamine microcapsules(Au NRs@PDA )^[56]。 Au nanoparticles and polydopamine simultaneously exert photothermal effect and show good anticancer effect in vitro under near-infrared laser irradiation.Moreover,Au NRs@PDA microcapsules have excellent biocompatibility,high drug loading rate and laser-triggered drug controlled release performance,showing a good prospect for biomedical applications.Chemokinetic therapy uses H₂O₂overexpressed in the tumor microenvironment to produce hydroxyl radicals within the tumor to kill cancer cells through Fenton/Fenton-like reaction,which has high tumor specificity and low systemic toxicity.However,the low content of H₂O₂in the tumor microenvironment leads to the low efficiency of Fenton/Fenton-like reaction and poor catalytic efficiency,so chemokinetic therapy is often used in combination with other treatments to treat tumors.Wang et al.Prepared ZIF-8（Cu²⁺/ZIF-8）doped with Cu²⁺,and loaded doxorubicin as a chemotherapeutic drug onto Cu²⁺/ZIF-8 by metal ion coordination,and then modified by polydopamine to obtain DOX@Cu²⁺/ZIF-8@PDA microcapsules(DCZP )^[57]。 In the acidic environment of tumor,DCZP microcapsules release doxorubicin and Cu²⁺.On the one hand,the released Cu²⁺can consume 54%of GSH and destroy the redox balance in cells;On the other hand,the Cu⁺obtained from the reduction of GSH can catalyze the decomposition of H₂O₂to produce•OH with higher cytotoxicity.In addition,laser irradiation not only induced photothermal conversion to kill tumor cells,but also accelerated the release of doxorubicin,which was beneficial to the generation of Cu⁺,thus enhancing chemokinetic therapy.To sum up,DCZP microcapsules effectively inhibited tumor growth by promoting GSH consumption and the combination of chemotherapy-photothermotherapy-chemokinetic therapy 。

microwave thermotherapy(MWTT)has the advantages of non-invasiveness,deep penetration and less damage to normal tissues.For example,Tan et al.Used ionic liquid(IL)as a Microwave sensitizer and loaded it on polydopamine microcapsules to obtain IL-PDA microcapsules^[58]。 Mice treated with IL-PDA+MW had almost complete elimination of tumor volume by day 14,and there was no recurrence after 6 days of complete tumor removal.However,the tumor treated with microwave alone had a slight inhibitory effect in the first 2 days,but the tumor volume increased rapidly in the last 12 days;Tumors in the blank control group and IL-PDA alone showed continuous growth(fig.7).Further,Tang et al.Loaded doxorubicin on IL-PDA microcapsules for MWTT-chemotherapy combination therapy^[59]。 the loading rate of doxorubicin in IL-P DA-DOX microcapsules was about 10.79%.Without microwave treatment,DOX-IL-PDA microcapsules had a certain killing effect on HepG2 and HeLa cells,and the inhibition rate of HepG2 and HeLa cells increased with the increase of microcapsule concentration.Under the treatment of microwave radiation,with the increase of the concentration of IL-PDA-DOX microcapsules,the cell viability decreased sharply,showing a better inhibition rate of tumor cells.IL-PDA microcapsules loaded with anticancer drugs combine chemotherapy with microwave hyperthermia for cancer treatment,which provides a very promising treatment method for future cancer clinical treatment。

metal nanoparticles have unique catalytic activity,but they are prone to agglomeration,resulting in reduced catalytic efficiency.polydopamine has excellent adhesion properties,film-forming ability and reduction properties,which can be reduced in situ to form metal nanoparticles and form a protective layer on the surface of nanoparticles to effectively prevent the agglomeration of nanoparticles,so it is widely used in the loading of metal nanoparticles.For example,Polydopamine-stabilized Au,Ag,Pt,Pd and other nanoparticles are widely used in catalytic reactions^[60]。 Tao et al.and Lin et al.Prepared Ag And Au loaded polydopamine microcapsules(Ag@PDA microcapsules,Au@PDA microcapsules),respectively,both of which showed excellent catalytic performance for methylene blue dye^[30][61]。 the Prepared metal is embedded in the polydopamine shell,thus showing better stability,recyclability,and reusability compared with the materials loaded with metal nanoparticles on the surface of polydopamine.Further,Zhou et al.prepared bimetallic Au@Ag@PDA microcapsule catalyst^[62]。 It was found that the redox coupling between dopamine and Ag⁺was able to induce the growth of Ag shell with adjustable thickness on Au nanoparticles,and finally Au@Ag@PDA microcapsules were obtained(Fig.8 A).Au@Ag@P DA microcapsules showed excellent catalytic activity for the reduction of 4-nitrophenol under the action of NaBH₄.And,the catalytic activity of bimetallic Au@Ag@PDA microcapsules was significantly improved than that of monometallic Au or Ag-loaded microcapsules,where the rate constant of Au@Ag@PDA microcapsules was（0.050 min^-1）,which was more than twice that of Au（0.020 min⁻¹）and Ag（0.023 min^-1）monometals(Fig.8 B).Further study showed that the Au@Ag shell structure had a synergistic effect,which effectively promoted the enhancement of catalytic activity.In addition,the Au@Ag@PDA microcapsules showed no obvious signs of shedding in six consecutive use cycles,and the conversion of 4-nitrophenol was still close to 100%after 2 H of continuous reaction(Fig.8C )。

Enzymes,as natural catalysts,can effectively catalyze a variety of chemical reactions.The combination of polydopamine and multi-enzyme system is beneficial to the realization of efficient enzyme-linked reaction.Hosta-Rigau et al.Loaded poly(L-lysine)/polymethacrylate copolymer（PLL/PMA_C）on the SiO₂core as a precursor layer,then deposited enzyme-carrying liposome and PMA_Cseparation layer on its surface,further coated the polydopamine shell and removed the SiO₂template core to obtain enzyme-carrying liposome polydopamine microcapsules^[63]。 The polydopamine microcapsule can be used as an artificial cell mimetic,in which the liposome subchamber is used as a partition system to encapsulate three different enzymes,namely uricase(UR),horseradish peroxidase(HRP)and ascorbate oxidase(AO),effectively realizing a double-enzyme coupling reaction and a single-enzyme conversion,and promoting the application of the cell mimetic as a disease treatment carrier and a biosensor.Wang et al.Used the prepared hybrid alginate microcapsules（Alg@PDA@SiO₂）for asymmetric biosynthesis of encapsulated(S)-1-phenylethanol in yeast cells^[64]。 Alginic acid microcapsules(Alg microcapsules)were formed by ionic crosslinking of alginate and Ca²⁺,and then coated with polydopamine shell to prepare Alg@PDA microcapsules,and silica nanoparticles were deposited to obtain Alg@PDA@SiO₂microcapsules.Among them,polydopamine can enhance the biocatalytic efficiency of encapsulated yeast cells,and SiO₂not only regulates the mass diffusion in the biocatalytic process,but also enhances the long-term mechanical and chemical stability of microcapsules.During 24 H of asymmetric reduction,the synthesis yield of Alg@PDA@SiO₂microencapsulated cells was 1.75 times higher than that of Alg microencapsulated cells.Moreover,the Alg@PDA@SiO₂microcapsules can still maintain a high yield after six times of recycling 。

Bacterial infections and related diseases caused by implanted medical devices seriously affect human health and disease treatment.Therefore,it is urgent to develop surface modification technologies that can effectively reduce bacterial adhesion and kill bacteria.The unique adhesion properties of polydopamine make it a new type of antibacterial material.Moreover,polydopamine is rich in catechol and amino groups,which is beneficial to the interfacial chemical modification of materials.For example,Ag⁺can be reduced in situ on the surface of polydopamine to form Ag nanoparticles,thereby establishing an antibacterial interface.In addition,polydopamine itself also has certain antibacterial effect.Dopamine is oxidized and self-polymerized on the surface of Escherichia coli to form polydopamine,and the barrier effect of the polydopamine coating not only reduces the permeability of nutrients needed by Escherichia coli,but also limits the space for bacterial growth;With the passage of time,bacteria are permanently sealed in the polydopamine shell,and their growth and proliferation are inhibited,thus achieving the effect of inhibiting bacterial growth and even killing bacteria 。

In dopamine-based nano-antibacterial materials,polydopamine is mainly used as a support or connector to assist other antibacterial active ingredients to play an antibacterial role.For example,antibacterial active substances such as precious metals,antibiotics and quaternary ammonium salts can be loaded on the surface of polydopamine by physical adsorption or chemical bonding,so as to achieve controlled release,bacterial inhibition and other effects^[65]。 Cu²⁺is an important component of biological protein or enzyme,which has excellent antibacterial effect and cytotoxicity,and its preparation cost is low.However,the antibacterial effect of Cu²⁺is longer,and it will produce a certain degree of toxicity when the concentration is high.Therefore,researchers have effectively controlled the release rate of Cu²⁺by combining Cu²⁺with polydopamine coating to achieve mild and long-lasting antibacterial effect.Yeroslavsky et al.Successfully prepared polydopamine microcapsules using n-dodecane as a template after sonication for 12 min^[66]。 Furthermore,the preparation time of microcapsules can be shortened to 6 min by adding CuSO₄in the reaction solution.It was found that Cu-PDA microcapsules could efficiently kill S.Aureus under the chelation of Cu²⁺.When the 3.3 mg/mL CuSO₄is added in the synthesis process,the bacteriostatic rate reaches 99.9%;Even with the addition of 0.5 mg/mL CuSO₄,the bacteriostatic rate can still reach 89.5%.However,the antibacterial rate of pure polydopamine microcapsules without copper loading was only 20%.Further,they prepared composite Cu/Ag-PDA microcapsules by sonochemical method,in which copper was embedded in the polydopamine microcapsule shell in the form of Cu^2+/1+chelation,and silver was loaded on the core layer in the form of Ag^0[67]。 At 37℃,the release rate of copper ions from the shell is faster,while the release rate of silver from the core is slower.the results showed that Ag-PDA microcapsules had antibacterial activity against Staphylococcus aureus,Pseudomonas aeruginosa,Streptococcus mutans and Escherichia coli,while Cu-PDA microcapsules had antibacterial activity against the first three strains,but had no obvious effect on Escherichia coli.the Cu/Ag-PDA microcapsules compounded with copper and silver showed enhanced antibacterial activity against the four bacteria,realizing the multimodal synergistic antibacterial activity of the two metals(Fig.9)。

Natural antibacterial agents have many advantages,such as good antibacterial effect,wide source,low price and so on.eugenol is a phenolic compound extracted from the flower buds or fruits of clove plants,which can inhibit the growth and reproduction of bacteria and has broad-spectrum antibacterial properties.Chen Ruru et al.Obtained polydopamine Eugenol(PDA@EO)microcapsules by emulsion template-interfacial polymerization^[68]。 PDA@EO microcapsules were spherical and uniform In size,and the entrapment efficiency of eugenol was 25.35%,and the entrapment amount was 0.6288 mg/mg;the cumulative release rate of eugenol can reach 90.43%,and the release rate increases with the increase of temperature.the study showed that the antibacterial activity of PDA@EO microcapsules against Staphylococcus aureus and Escherichia coli was increased by 36.84%and 35.52%,respectively,compared with the antibacterial activity of free eugenol.This may be due to the gradual volatilization of free eugenol with time,which leads to the gradual decrease of antibacterial activity;However,the encapsulated eugenol in PDA@EO microcapsules was able to achieve slow release and sustained antibacterial effect.When the mass concentration of the microcapsule is 2.0 mg/mL,the antibacterial activity against Staphylococcus aureus and Escherichia coli can reach 99%.in addition,PDA@EO microcapsules also have good thermal stability and biocompatibility。

pests and diseases are one of the most important problems in the process of crop production.the proliferation of pests and diseases will cause serious damage to crops,resulting in a significant reduction in yield.Rational use of pesticides can effectively control pests and diseases,reduce crop losses,and improve the yield and quality of agricultural products.the use of microencapsulated pesticides can not only reduce the frequency of pesticide use,reduce environmental pollution and ensure the safety of sprayers,but also prevent the early degradation of active ingredients and effectively improve the utilization rate of pesticides.Therefore,microcapsules have been widely developed and applied in the field of pesticides.For example,the polydopamine microcapsules(Av@PDA)prepared by Jia et al.Had a loading rate of avermectin as high as 66.5%w/w,which effectively reduced the volatilization of avermectin(Fig.10)^[69]。 Moreover,the cumulative release of Av@PDA microcapsules was only 29.3%within 220 H,which greatly prolonged the retention time of abamectin on the crop surface.the release rate of abamectin increased with pH value,and the release amount was about 19%w/w at pH 3.0 and 71%w/w at pH 9.0 for 120 H.at different pH values,the electrostatic interaction between the polydopamine shell and avermectin molecules is different due to the different surface charges:when pH>3,the avermectin shell is negatively charged,while the polydopamine shell is positively charged by protonation at low pH values,showing electrostatic attraction;However,In a high pH environment,the amino group of polydopamine is deprotonated so that it is negatively charged,which shows electrostatic repulsion(Fig.10B).In addition,the avermectin release rate of Av@PDA microcapsules increased gradually with the increase of temperature.at high temperature,the diffusion of avermectin molecules through the polydopamine shell was enhanced,and the avermectin molecules became easier and faster to release.the cumulative release of avermectin was 27.43%,49.27%and 92.07%at 27,37 and 47°C,respectively(fig.10 C).In addition,the polydopamine coating also shields UV radiation,thereby protecting abamectin from photodegradation.Furthermore,Sheng et al.Grafted polydopamine microcapsules(PDMAEMA-g-PDA)on poly(dimethylaminoethyl methacrylate)film to obtain a temperature-controlled release abamectin system^[70]。 The temperature-controlled release behavior of avermectin from Av@PDMAEMA-g-PDA microcapsules was opposite to that of Av@PDA microcapsules due to the temperature sensitivity and biocompatibility of grafted PDMAEMA.In Av@PDMAEMA-g-PDA microcapsules,the cumulative release rate of avermectin decreased with the increase of temperature,and the release performance of Av@PDMAEMA-g-PDA was better When the temperature(such as 30℃)was lower than the lower critical solution temperature(LCST)of PDMAEMA.This is due to the swelling of the PDMAEMA polymer,which loosens the structure and therefore makes it easier to release abamectin.when the temperature(such as 50℃)is higher than the LCST of PDMAEMA,the heat-sensitive PDMAEMA polymer as a nanoreactor selectively shuts off the release of the loaded drug.the temperature-controlled drug release properties of Av@PDMAEMA-g-PDA microcapsules make them promising for controlled drug release and agriculture-related applications。

the essential oil can be used not only as a botanical pesticide,but also as a solvent for herbicides,and has a high encapsulation efficiency of active ingredients.Tang et al.Prepared polydopamine microcapsules with a shell thickness of about 95 nm on The surface of Pickering emulsion by oxidative self-polymerization of dopamine^[71]。 the drug loading and entrapment efficiency of 2,4-dichlorophenoxyacetic acid(2,4-D)In polydopamine microcapsules can be effectively adjusted by controlling the content of dopamine.When the dosage of dopamine was 1200 mg,the drug loading was 13.4%,the entrapment efficiency was 74.89%,and the optimal drug release behavior was observed.this method minimizes the use of toxic solvents and synthetic surfactants,improves the encapsulation efficiency of active ingredients,and is an effective sustained-release strategy for pesticides.in addition,commercial and traditionalλ-cyhalothrin(LC)microencapsulated pesticide formulations often require complex synthetic reaction processes as well as specific organic solvents.To This end,Zou et al.Prepared LC-PDA microcapsules by loading LC on the surface of polydopamine^[72]。 the preparation process of the microcapsule is simple,and organic solvent and surfactant are not needed.The LC-PDA microcapsules have uniform size,high drug loading rate(>50.0%w/w),good stability and drug sustained release.In the study of killing houseflies,the biological activity and long-term efficacy of LC-PDA microcapsules were significantly better than those of commercial preparations,and LC-PDA microcapsules were expected to be developed into an environmentally friendly and efficient commercial preparation。