Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes,such as natural cell membranes or subcellular structure-derived membranes.This strategy endows cloaked nanomaterials with improved interfacial properties,superior cell targeting,immune evasion potential,and prolonged duration of systemic circulation.Here,we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials.The structure,properties,and manner in which exosomes communicate with cells are first reviewed.This is followed by a discussion of the types of exosomes and their fabrication methods.We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering,regenerative medicine,imaging,and the treatment of neurodegenerative diseases.Finally,we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

Innovative hydrophobic/hydrophilic perfluoropolyether(PFPE)/polyvinylidene fluoride(PVDF)composite membrane for vacuum membrane distillation

Though membrane distillation(MD)has gained more and more attention in the field of desalination,the wetting phenomenon was still a non-negligible problem.In this work,a method combined dip-coating and UV in situ polymerization for preparing hydrophobic/hydrophilic perfluoropolyether(PFPE)/polyvinylidene fluoride composite membranes.This composite membrane consisted of a top thin hydrophobic coating layer and hydrophilic substrate membrane.In terms of anti-wetting properties,contact angle and liquid entry pressure of all composite membranes(except for those based on 0.45μm)exceeded 160°and 0.3 MPa,respectively.In particular,the desalination performance was tested in vacuum membrane distillation tests by feeding 3.5%(mass)saline solution(NaCl)at 60℃.The composite membranes with larger support pore size and lower PFPE content had higher membrane distillation flux.And for stability tests(testing the 0.22μm membrane coated by 5%(mass)PFPE),the highest MD flux29.08 kg·m^(-2)·h^(-1) and stable salt rejection(over 99.99%)during the period.Except that,the effects of coating material concentration and pore sizes of substrate membrane were also investigated for surface morphology and topography,porosity,mechanical strength and pore size characteristics.This work provided a simple and effective alternative to prepare excellent hydrophobic composite membranes for MD applications.

Fluorite Ce_(0.8)Sm_(0.2)O_(2-δ) porous layer coating to enhance the oxygen permeation behavior of a BaCo_(0.7)Fe_(0.2)Nb_(0.1)O_(3-δ) mixed conductor

Fluorite Ce0.8Sm0.2O2-δ（SDC） nanopowder with a crystallite size of 15 nm was synthesized by a co-precipitation method. An SDC porous layer was coated onto a BaCo0.7Fe0.2Nb0.1O3-δ（BCFN） mixed conductor to improve its oxygen transport behavior. The results show that the SDC-coated BCFN membrane exhibits a remarkably higher oxygen permeation flux（JO2） than the uncoated BCFN in the partial oxidation of coke oven gas（COG）. The maximum JO2 value of the SDC-coated BCFN is 18.28 mL ·min^-1·cm^-2 under a COG/air flux of 177 mL ·min^-1/353 mL ·min^-1 at 875℃ when the thickness of the BCFN membrane is 1 mm; this JO2 value is 23% higher than that of the uncoated BCFN membrane. This enhancement is likely because of the higher oxygen ionic conductivity of SDC, which supplies oxygen vacancies and accelerates oxygen exchange on the membrane/coating layer/gas three-phase boundary.

Enhancement of current density using effective membranes electrode assemblies for water electrolyser system

The goal of this study was to develop and design a composite proton exchange membrane（PEM） and membrane electrode assembly（MEA） that are suitable for the PEM based water electrolysis system. In particular,it focuses on the development of sulphonated polyether ether ketone（SPEEK） based membranes and caesium salt of silico-tungstic acid（Cs Si WA） matrix compared with one of the transition metal oxides such as titanium dioxide（TiO2）, silicon dioxide（SiO2） and zirconium dioxide（ZrO2）. The resultant membranes have been characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, ion exchange capacity（IEC）, water uptake and atomic force microscopy. Comparative studies on the performance of MEAs were also conducted utilizing impregnation-reduction and conventional brush coating methods. The PEM electrolysis performance of SPEEK-Cs Si WA-ZrO2 composite membrane was more superior than that of other membranes involved in this study. Electrochemical characterization shows that a maximum current density of 1.4 A/cm^2 was achieved at 60 °C, explained by an increased concentration of protonic sites available at the interface.

Plasma Modified Polypropylene Membranes as the Lithium-Ion Battery Separators

To reduce the thermal shrinkage of the polymeric separators and improve the safety of the Li-ion batteries,plasma treatment and plasma enhanced vapor chemical deposition（PECVD）of SiO_x-like are carried out on polypropylene（PP）separators,respectively.Critical parameters for separator properties,such as the thermal shrinkage rate,porosity,wettability,and mechanical strength,are evaluated on the plasma treated PP membranes.O_2 plasma treatment is found to remarkably improve the wettability,porosity and electrolyte uptake.PECVD SiO_x-like coatings are found to be able to effectively reduce the thermal shrinkage rate of the membranes and increase the ionic conductivity.The electrolyte-philicity of the Si Ox-like coating surface can be tuned by the varying O_2 content in the gas mixture during the deposition.Though still acceptable,the mechanical strength is reduced after PECVD,which is due to the plasma etching.

Current research progress on cell membrane decorated macroscopic biomaterials

The cell membranes,derived from natural sources,possesses unique physicochemical properties of phospholipid bilayers and biological functionalities of membrane proteins.This makes it an ideal biomimetic coating to enhance the in vivo circulation and retention time of micro/nanodrug carriers,provide targeted drug delivery effects,and neutralize bacterial toxins.Notably,recent studies have successfully coated various types of cell membranes onto the surfaces of macroscopic materials,such as electrospun fiber scaffolds and decellularized matrices,to promote tissue repair,modulate host responses to foreign materials,and alleviate inflammation.This review comprehensively summarizes the latest research progress in the modification of macroscopic biomaterials with cell membranes.The insights provided aim to serve as a valuable reference for the preparation of cell membrane biomimetic coatings and their applications in the field of tissue repair.

Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing

Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function.However,random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites,especially when applied to intracellular regions of transmembrane proteins.Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem.Herein,inside-out cell membrane camouflaged magnetic nanoparticles(IOCMMNPs)were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2.Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe_(3)O_(4)nanoparticles to prepare IOCMMNPs.The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay.Ultimately,two compounds,senkyunolide A and ligustilidel,were successfully captured,and their potential antiproliferative activities were further testified by pharmacological experiments.It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

Cell membrane-coated mesoporous silica nanorods overcome sequential drug delivery barriers against colorectal cancer

Local delivery of nanomedicines holds therapeutic promise for colorectal cancer(CRC).However,it presents tremendous challenges due to the existence of multiple physiological barriers,especially intracellular obstacles,including intracellular trafficking,subcellular accumulation,and drug release.Herein,we report a multifunctional nanoparticle(CMSNR)by wrapping the mesoporous silica nanorod with cell membrane derived from CRC cells for improved chemotherapy.Compared with their naked counterparts,the cell membrane endowed CMSNR with homotypic targeting and improved cellular uptake capacities.Due to the rod-like shape,CMSNR achieved superior colorectal mucus permeability,enhanced tumor accumulation,and boosted cellular uptake than their spherical counterparts.Moreover,the internalized CMSNR underwent robust intracellular trafficking and gained augmented motility toward the nucleus,leading to efficient perinuclear accumulation and a subsequent 5.6-fold higher nuclear accumulation of loaded drug than that of nanospheres.In the orthotopic colorectal tumor-bearing nude mice,rectally administrated mefuparib hydrochloride(MPH)-loaded CMSNR traversed the colorectal mucus,penetrated the tumor tissue,and successfully aggregated in the perinuclear region of cancer cells,thus exhibiting significantly improved antitumor outcomes.Our findings highlight the shape-based design of cell membranecoated nanoparticles that can address sequential drug delivery barriers has a promising future in cancer nanomedicine.

Ectopic mineralization-inspired cell membrane-based matrix vesicle analogs for in-depth remineralization of dentinal tubules for treating dentin hypersensitivity

The invasion of etched dentinal tubules(DTs)by external substances induces dentin hypersensitivity(DH).The deep and compact occlusion of DTs is highly desirable for treating DH but still challenging due to the limited penetrability and mineralization capacities of most current desensitizers.Matrix vesicles(MVs)participate in the regulation of ectopic mineralization.Herein,ectopic MV analogs are prepared by employing natural cell membranes to endow mineral precursors with natural biointerfaces and integrated biofunctions for stimulating dentin remineralization.The analogs quickly access DTs(>20μm)in only 5 min and further penetrate deep into the interior of DTs(an extraordinary~200μm)in 7 days.Both in vitro and in vivo studies confirm that the DTs are efficiently sealed by the newly formed minerals(>50μm)with excellent resistance to wear and acid erosion,which is significantly deeper than most reported values.After repair,the microhardness of the damaged dentin can be recovered to those of healthy dentin.For the first time,cell membrane coating nanotechnology is used as a facile and efficient therapy for in-depth remineralization of DTs in treating DH with thorough and long-term effects,which provides insights into their potential for hard tissue repair.

An iron-based metal-organic framework nanoplatform for enhanced ferroptosis and oridonin delivery as a comprehensive antitumor strategy

Ferroptosis is a recently discovered pathway for regulated cell death pathway.However,its efficacy is affected by limited iron content and intracellular ion homeostasis.Here,we designed a metalorganic framework(MOF)-based nanoplatform that incorporates calcium peroxide(CaO2)and oridonin(ORI).This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis,thereby enhancing ferroptosis therapy.Fused cell membranes(FM)were used to modify nanoparticles(ORI@CaO2@Fe-TCPP,NPs)to produce FM@ORI@CaO2@Fe-TCPP(FM@NPs).The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously,working in tandem with Fe3t to induce ferroptosis.Photodynamic therapy(PDT)guided by porphyrin(TCPP)significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species(ROS).This selfamplifying strategy promoted robust ferroptosis,which could work synergistically with FM-mediated immunotherapy.In vivo experiments showed that FM@NPs inhibited 91.57%of melanoma cells within six days,a rate 5.6 times higher than chemotherapy alone.FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity.Thus,this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.

Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications.However,administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system(MPS).In this study,we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues.The fabricated nanoparticles(TM-CQ/NPs)were coated with fibroblast cell membrane expressing tumor necrosis factor(TNF)-related apoptosis inducing ligand(TRAIL).Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages,but increased the nanoparticle uptake in tumor cells.Importantly,this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors.Meanwhile,the encapsulated chloroquine(CQ)further suppressed the uptake of nanoparticles by macrophages,and synergized with TRAIL to induce tumor cell apoptosis.The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy.Together,our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

Cytokine nanosponges suppressing overactive macrophages and dampening systematic cytokine storm for the treatment of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis(HLH)is a highly fatal condition with the positive feedback loop between continued immune cell activation and cytokine storm as the core mechanism to mediate multiple organ dysfunction.Inspired by macrophage membranes harbor the receptors with special high affinity for proin-flammation cytokines,lipopolysaccharide(LPS)-stimulated macrophage membrane-coated nanoparticles(LMNP)were developed to show strong sponge ability to both IFN-γand IL-6 and suppressed overactivation of macrophages by inhibiting JAK/STAT signaling pathway both in vitro and in vivo.Besides,LMNP also efficiently alleviated HLH-related symptoms including cytopenia,hepatosplenomegaly and hepatorenal dysfunction and save the life of mouse models.Furthermore,its sponge effect also worked well for five human HLH samples in vitro.Altogether,it’s firstly demonstrated that biocompatible LMNP could dampen HLH with high potential for clinical transformation,which also provided alternative insights for the treatment of other cytokine storm-mediated pathologic conditions such as COVID-19 infection and cytokine releasing syndrome during CAR-T therapy.

Dendritic cell-mimicking scaffolds for ex vivo T cell expansion

We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells,long duration of T cell tethering,and DC-specific co-stimulatory cues.The DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands,anti-CD3(αCD3)and anti-CD28(αCD28)antibodies,followed by adsorption of releasable interleukin-2(IL-2).The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in vivo.We demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared toαCD3/αCD28-func-tionalized Dynabead.More importantly,major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing ability.In addition,most of the expanded T cells(~97%)can be harvested from the scaffold by density gradient centri-fugation.Overall,the DC-mimicking scaffold offers a scalable,modular,and customizable platform for rapid expansion of highly functional T cells for ACT.

MicroRNA-208a silencing against myocardial ischemia/reperfusion injury mediated by reversibly camouflaged biomimetic nanocomplexes

MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.