Tumor-targeted self-assembled micelles reducing PD-L1 expression combined with ICIs to enhance chemo-immunotherapy of TNBC

Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.

Interfacial Modification of NiO_(x)by Self-assembled Monolayer for Efficient and Stable Inverted Perovskite Solar Cells

NiO_(x)as a hole transport material for inverted perovskite solar cells has received great attention owing to its high transparency,low fabrication temperature,and superior stability.However,the mismatched energy levels and possible redox reactions at the NiO_(x)/perovskite interface severely limit the performance of NiO_(x) based inverted perovskite solar cells.Herein,we introduce a p-type self-assembled monolayer between NiO_(x)and perovskite layers to modify the interface and block the undesirable redox reaction between perovskite and NiO_(x)The selfassembled monolayer molecules all contain phosphoric acid function groups,which can be anchored onto the NiOr surface and passivate the surface defect.Moreover,the introduction of self-assembled monolayers can regulate the energy level structure of NiO_(x),reduce the interfacial band energy offset,and hence promote the hole transport from perovskite to NiO_(x)layer.Consequently,the device performance is significantly enhanced in terms of both power conversion efficiency and stability.

Mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate reverse micelles

The liquid-liquid extraction method using reverse micelles can simultaneously extract lipid and protein of oilseeds,which have become increasingly popular in recent years.However,there are few studies on mass transfer processes and models,which are helpful to better control the extraction process of oils and proteins.In this paper,mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate(AOT)/isooctane reverse micelles was investigated.The effects of stirring speed(0,70,140,and 210 r/min),temperature of extraction(30,35,40,45,and 50℃),peanut flour particle size(0.355,0.450,0.600,and 0.900 mm)and solidliquid ratio(0.010,0.0125,0.015,0.0175,and 0.020 g/mL)on extraction rate were examined.The results showed that extraction rate increased with temperature rising,particle size reduction as well as solid-liquid ratio increase respectively,while little effect of stirring speed(P>0.05)was observed.The apparent activation energy of extraction process was calculated as 10.02 kJ/mol and Arrhenius constant(A)was 1.91 by Arrhenius equation.There was a linear relationship between reaction rate constant and the square of the inverse of initial particle radius(1/r_(0)^(2))(P<0.05).This phenomenon and this shrinking core model were anastomosed.In brief,the extraction process was controlled by the diffusion of protein from the virgin zone interface of particle through the reacted zone and it was in line with the first order reaction.Mass transfer kinetics of peanut protein extracted by reverse micelles was established and it was verified by experimental results.The results provide an important theoretical guidance for industrial production of peanut protein separation and purification.

Role of self-assembled molecules’anchoring groups for surface defect passivation and dipole modulation in inverted perovskite solar cells

Inverted perovskite solar cells have gained prominence in industrial advancement due to their easy fabrication,low hysteresis effects,and high stability.Despite these advantages,their efficiency is currently limited by excessive defects and poor carrier transport at the perovskite-electrode interface,particularly at the buried interface between the perovskite and transparent conductive oxide(TCO).Recent efforts in the perovskite community have focused on designing novel self-assembled molecules(SAMs)to improve the quality of the buried interface.However,a notable gap remains in understanding the regulation of atomic-scale interfacial properties of SAMs between the perovskite and TCO interfaces.This understanding is crucial,particularly in terms of identifying chemically active anchoring groups.In this study,we used the star SAM([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)as the base structure to investigate the defect passivation effects of eight common anchoring groups at the perovskite-TCO interface.Our findings indicate that the phosphonic and boric acid groups exhibit notable advantages.These groups fulfill three key criteria:they provide the greatest potential for defect passivation,exhibit stable adsorption with defects,and exert significant regulatory effects on interface dipoles.Ionized anchoring groups exhibit enhanced passivation capabilities for defect energy levels due to their superior Lewis base properties,which effectively neutralize local charges near defects.Among various defect types,iodine vacancies are the easiest to passivate,whereas iodine-substituted lead defects are the most challenging to passivate.Our study provides comprehensive theoretical insights and inspiration for the design of anchoring groups in SAMs,contributing to the ongoing development of more efficient inverted perovskite solar cells.

Factors resisting protein adsorption on hydrophilic/hydrophobic self-assembled monolayers terminated with hydrophilic hydroxyl groups

The hydroxyl-terminated self-assembled monolayer(OH-SAM),as a surface resistant to protein adsorption,exhibits substantial potential in applications such as ship navigation and medical implants,and the appropriate strategies for designing anti-fouling surfaces are crucial.Here,we employ molecular dynamics simulations and alchemical free energy calculations to systematically analyze the factors influencing resistance to protein adsorption on the SAMs terminated with single or double OH groups at three packing densities(∑=2.0 nm^(-2),4.5 nm^(-2),and 6.5 nm^(-2)),respectively.For the first time,we observed that the compactness and order of interfacial water enhance its physical barrier effect,subsequently enhancing the resistance of SAM to protein adsorption.Notably,the spatial hindrance effect of SAM leads to the embedding of protein into SAM,resulting in a lack of resistance of SAM towards protein.Furthermore,the number of hydroxyl groups per unit area of double OH-terminated SAM at ∑=6.5 nm^(-2) is approximately 2 to 3 times that of single OH-terminated SAM at ∑=6.5 nm^(-2) and 4.5 nm^(-2),consequently yielding a weaker resistance of double OH-terminated SAM towards protein.Meanwhile,due to the structure of SAM itself,i.e.,the formation of a nearly perfect ice-like hydrogen bond structure,the SAM exhibits the weakest resistance towards protein.This study will complement and improve the mechanism of OH-SAM resistance to protein adsorption,especially the traditional barrier effect of interfacial water.

Morphological Evolution of Self-Assembled Sodium Dodecyl Sulfate/Dodecyltrimethylammonium Bromide@Epoxy-β-Cyclodextrin Supramolecular Aggregates Induced by Temperature

Bio-based cyclodextrins(CDs)are a common research object in supramolecular chemistry.The special cavity structure of CDs can form supramolecular self-assemblies such as vesicles and microcrystals through weak interaction with guest molecules.The different forms of supramolecular self-assemblies can be transformed into each other under certain conditions.The regulation of supramolecular self-assembly is not only helpful to understand the self-assembly principle,but also beneficial to its application.In the present study,the self-assembly behavior of epoxy-β-cyclodextrin(EP-β-CD)and mixed anionic and cationic surfactant system(sodium dodecyl sulfate/dodecyltrimethylammonium bromide,SDS/DTAB)in aqueous solution was studied.Morphological and particle size characterization found that the SDS/DTAB@EP-β-CD complex,as the basic building unit,self-assembled into worm-like micelles at lower temperatures and vesicles at higher temperatures.Nuclear magnetic resonance(NMR)and Fourier transform infrared spectroscopy(FT-IR)analysis revealed that the driving force for the formation of vesicles and worm-like micelles was the hydrogen bonds between EP-β-CD molecules,while water molecules played an important role in promoting vesicle formation between SDS/DTAB@EP-β-CD units.Herein,the mechanism of the morphologic transformation of SDS/DTAB@EP-β-CD supramolecular aggregates induced by temperature was elucidated by exploring the self-assembly process,which may provide an excellent basis for the development of delivery carriers.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Intelligent responsive self-assembled micro-nanocapsules:Used to delay gel gelation time

In the application of polymer gels to profile control and water shutoff,the gelation time will directly determine whether the gel can"go further"in the formation,but the most of the methods for delaying gel gelation time are complicated or have low responsiveness.There is an urgent need for an effective method for delaying gel gelation time with intelligent response.Inspired by the slow-release effect of drug capsules,this paper uses the self-assembly effect of gas-phase hydrophobic SiO_(2) in aqueous solution as a capsule to prepare an intelligent responsive self-assembled micro-nanocapsules.The capsule slowly releases the cross-linking agent under the stimulation of external conditions such as temperature and pH value,thus delaying gel gelation time.When the pH value is 2 and the concentration of gas-phase hydrophobic SiO_(2) particles is 10%,the gelation time of the capsule gel system at 30,60,90,and 120℃is12.5,13.2,15.2,and 21.1 times longer than that of the gel system without containing capsule,respectively.Compared with other methods,the yield stress of the gel without containing capsules was 78 Pa,and the yield stress after the addition of capsules was 322 Pa.The intelligent responsive self-assembled micronanocapsules prepared by gas-phase hydrophobic silica nanoparticles can not only delay the gel gelation time,but also increase the gel strength.The slow release of cross-linking agent from capsule provides an effective method for prolongating the gelation time of polymer gels.

Self-Assembled Nanomicelles of Affibody-Drug Conjugate with Excellent Therapeutic Property to Cure Ovary and Breast Cancers

Affibody molecules are small nonimmunoglobulin affinity proteins,which can precisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them seriously limited their application in drug targeted delivery for cancer therapy.Here an amphiphilic affibody-drug conjugate is self-assembled into nanomicelles to prolong circulation time for targeted cancer therapy.As an example of the concept,the nanoagent was prepared through molecular self-assembly of the amphiphilic conjugate of Z_(HHR2:342)-Cys with auristatin E derivate,where the affibody used is capable of binding to the human epidermal growth factor receptor 2(HER2).Such a nanodrug not only increased the blood circulation time,but also enhanced the tumor targeting capacity(abundant affibody arms on the nanoagent surface) and the drug accumulation in tumor.As a result,this affibody-based nanoagent showed excellent antitumor activity in vivo to HER2-positive ovary and breast tumor models,which nearly eradicated both small solid tumors(about 100 mm^(3)) and large established tumors(exceed 500 mm^(3)).The relative tumor proliferation inhibition ratio reaches 99.8% for both models.

Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.

Construction of curcumin-loaded micelles and evaluation of the anti-tumor effect based on angiogenesis

Objective:Inhibition of tumor angiogenesis has become a new targeted tumor therapy.In this study,we established a micellar carrier with a tumor neovascularization-targeting effect modified by the neovascularization-targeting peptide NGR.Methods:The targeted polymer poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PEG-PLGA)modified with Asn–Gly–Arg(NGR)peptide was prepared and characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectrometry.NGR-PEG-PLGA was used to construct curcumin(Cur)-loaded micelles by the solvent evaporation method.The physicochemical properties of the micelles were also investigated.Additionally,we evaluated the antitumor efficacy of the polymer micelles(PM)using in vitro cytology experiments and in vivo animal studies.Results:The particle size of Cur-NGR-PM was 139.70±2.51 nm,and the drug-loading capacity was 14.37±0.06%.In vitro cytological evaluation showed that NGR-modified micelles showed higher cellular uptake through receptor-mediated endocytosis pathways than did unmodified micelles,leading to the apoptosis of tumor cells.Then,in vivo antitumor experiments showed that the modified micelles significantly inhibited tumor growth and were safe.Conclusions:NGR-modified micelles significantly optimized the therapeutic efficacy of Cur.This strategy offers a viable avenue for cancer treatment.

Optically active micelles from self-assembly of MPEG-b-PMALM copolymer in water

Reported here is fabrication of optically active micelles with broad range of morphologies in water, such as spheres, cylinders, and vesicles, from self-assembly of poly（ethylene glycol） monomethyl ether-b-poly- （methacryloyl-L-leucine methyl ester） （MPEG-b-PMALM） copolymer, which was prepared via atom transfer radical polymerization （ATRP） from vinyl monomer bearing chiral amino acid moieties, N-methacryloyl L-leucine methyl ester （MALM）, using bromine （Br） end-capped poly（ethylene golycol） monomethylether （MPEG-Br） as macroinitiator in the presence of CuBr/Me6TREN as catalytic system.

Antibiotic-based small molecular micelles combined with photodynamic therapy for bacterial infections

The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics.Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs,but the mass proportion of carriers generally exceeds 90%of the nano-drug,resulting in low drug loading and limited therapeutic output.Herein,we fabricated a nanocarrier using antibiotics as the building blocks,minimizing the use of carriermaterials,significantly increasing the drug loading content and treatment effect.Firstly,we conjugated betaine carboxylate with ciprofloxacin(CIP)through an ester bond to form the amphiphilic conjugate(CIP-CB),which self-assembled into micelles(CIP-CBMs)in aqueous solutions,with a CIP loading content as high as 65.4%and pH-induced surface charge reversal properties.Secondly,a model photosensitizer(5,10,15,20-tetraphenylporphyrin(TPP))was encapsulated in CIP-CBMs,generating infection-targeted photodynamic/antibiotic combined nanomedicines(denoted as TPP@CIP-CBMs).Upon accumulation at infection sites or in deep bacterial biofilms,the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP,leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo.

Active straining engineering on self-assembled stacked Ni-based hybrid electrode for ultra-low overpotential

Generating sufficient strains on metal surfaces are highly challenging owing to that most metals can deform plastically to relax the strains on the surfaces.In this work,we developed a facile but highly efficient stacked deposition strategy to in situ activation and reconstruction of NiO/NiOOH on Ni matrix,following with the migration of Fe ions to NiOOH.The Fe sites on the Ni/NiO/NiOOH facilitate the formation of the stable*OH oxygenated intermediates,and the Ni matrix in the catalyst provides the catalyst excellent stability.The oxygen evolution reaction(OER)performance of the stacked NiFe-5 with compressive strain displays the strengthened binding to oxygenated intermediates and superior OER activity,the ultralow overpotentials of 162 versus reversible hydrogen electrode at 10 mA cm^(-2).On the other hand,the Ni-5 without the incorporation of Fe has shown an outstanding hydrogen evolution reaction(HER)activity,affording an overpotential of 47 mV at 10 mA cm^(-2).The NiFe-5‖Ni-5 enables the overall water splitting at a voltage of 1.508 V to achieve 20 mA cm^(-2) with remarkable durability.The stacked deposition strategy improves binding strength of Ni-based catalysts to oxygenated intermediates via generating compressive strain,causing high catalytic activities on OER and HER.

Preparation of adhesive resveratrol micelles and determination of drug content

Objective:Resveratrol polymer micelles with tissue adhesion were prepared and the content of resveratrol in the micelles was determined by HPLC.Method:The micelle adhesion experiment was carried out by polylysine orifice plate experiment and small animal fluorescence imaging method,and the micelle prescription was optimized to obtain resveratrol micelles with good adhesion.The separation was performed on a Shiseido SPOLAR C18 column(150 mm×4.6 mm,5μm)with methanol-water(42:58)as the mobile phase.The flow rate was 1.0 mL·min^(-1),the detection wavelength was 305 nm,the column temperature was 35℃,and the injection volume was 10μL.Results:Resveratrol micelles prepared with F127 alone had the best adhesion.The peak area and concentration of resveratrol had a good linear relationship in the concentration range of 10~200μg/mL(r=0.9996).The specificity,precision,recovery and stability all met the methodological requirements.Conclusion:In this experiment,resveratrol micelles with tissue adhesion were successfully prepared,and a method for the determination of resveratrol content in micelles was established.The method is accurate,rapid and simple.

Intelligent self-assembly prodrug micelles loading doxorubicin in response to tumor microenvironment for targeted tumors therapy

Compared with physical drug-loaded nanocarriers,polymeric prodrug micelles have many advantages such as high drug loading and enhanced stability in blood,so they have great potential in cancer therapy.However,these micelles have a big disadvantage,which cannot achieve long-term circulation in vivo and high absorption of tumor cells simultaneously,resulting in low administration efficiency and poor therapeutic effect on cancer.To solve problems of traditional polymeric prodrug micelles,novel polymeric micelles with tumor microenvironment response were designed in this work.The prodrug formed by covalently linking D-α-tocopherol polyethylene glycol succinate(TPGS_(3350)),peptide(Pep),and doxorubicin(DOX)(TPGS_(3350)-Pep-DOX)was self-assembled into micelles by encapsulating DOX physically.When the micelles entered the tumor tissue,the long-chain polyethylene glycol(PEG)was sensitively cut by the matrix metalloproteinase 2/9(MMP2/9)enzyme,exposing the targeting molecule folate,then it entered the cell through the endocytic pathway mediated by the folate receptor.The drug loading content,encapsulation efficiency,critical micelle concentration,and invitro release of the micelles invented in this study were measured to characterize their properties.The particle size and zeta potential of micelles were characterized by dynamic light scattering.Images were scanned by transmission electron microscopes.In vitro cytotoxicity,cellular uptake,and in vivo antitumor effect evaluation experiments were measured to show that smart micelles have made much progress in material chemistry and drug delivery,making it possible to apply a stimulus-response carrier drug delivery system in clinical application.

Au@Ag Core-shell Nanorods Self-assembled on Polyelectrolyte Multilayers for Ultra-High Sensitivity SERS Fiber Probes

We demonstrated a chemical process in the fabrication of a SERS fiber probe with an ultrahigh sensitivity.The synthesis was carried out by preparing Au@Ag core-shell nanorods (Au@Ag-NRs) selfassembled on polyelectrolyte (PE) multilayers,for which Au@Ag-NRs were controlled by adjusting the silver layer thickness.The effect of silver layer thickness of Au@Ag-NRs on the SERS performance of the fiber probe was investigated.The SERS fiber probe shows the best performance when the silver layer thickness is controlled at 8.57 nm.Under the condition of optimizing silver layer thickness,the fiber probe exhibits ultra-high sensitivity (i e,10^(-10) M crystalline violet,CV),good reproducibility (i e,RSD of 3.5%) and stability.Besides,electromagnetic field distribution of the SERS fiber probe was also investigated.The strongest enhancement is found within the core of fiber,whereas a weakened electromagnetic field exists in the fiber cladding layer.The SERS fiber probe can be a good candidate in ultra-trace detection for biomedical and environmental areas.

Polyelectrolyte complex micelles by self-assembly of polypeptide-based triblock copolymer for doxorubicin delivery

Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol)-b-poly(L-aspartic acid)(PLD-b-PEG-b-PLD),spontaneously self-assembled with doxorubicin(DOX)via electrostatic interactions to form spherical micelles with a particle size of 60e80 nm(triblock ionomer complexes micelles,TBIC micelles).These micelles exhibited a high loading capacity of 70%(w/w)at a drug/polymer ratio of 0.5 at pH 7.0.They showed pH-responsive release patterns,with higher release at acidic pH than at physiological pH.Furthermore,DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line.Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis.These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats.Overall,these findings indicate that PLDb-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.

Self-assembly of perovskite nanocrystals:From driving forces to applications

Self-assembly of metal halide perovskite nanocrystals(NCs)into superlattices can exhibit unique collective properties,which have significant application values in the display,detector,and solar cell field.This review discusses the driving forces behind the self-assembly process of perovskite NCs,and the commonly used self-assembly methods and different self-assembly structures are detailed.Subsequently,we summarize the collective optoelectronic properties and application areas of perovskite superlattice structures.Finally,we conclude with an outlook on the potential issues and future challenges in developing perovskite NCs.

Alcohol solvent effect on the self-assembly behaviors of lignin oligomers

The interactions between lignin oligomers and solvents determine the behaviors of lignin oligomers self-assembling into uniform lignin nanoparticles(LNPs).Herein,several alcohol solvents,which readily interact with the lignin oligomers,were adopted to study their effects during solvent shifting process for LNPs’production.The lignin oligomers with widely distributed molecular weight and abundant guaiacyl units were extracted from wood waste(mainly consists of pine wood),exerting outstanding self-assembly capability.Uniform and spherical LNPs were generated in H_(2)O-n-propanol cosolvent,whereas irregular LNPs were obtained in H_(2)O-methanol cosolvent.The unsatisfactory self-assembly performance of the lignin oligomers in H_(2)O-methanol cosolvent could be attributed to two aspects.On one hand,for the initial dissolution state,the distinguishing Hansen solubility parameter and polarity between methanol solvent and lignin oligomers resulted in the poor dispersion of the lignin oligomers.On the other hand,strong hydrogen bonds between methanol solvent and lignin oligomers during solvent shifting process,hindered the interactions among the lignin oligomers for self-assembly.