Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes ...Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.展开更多
We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepa...We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepared(by CM-β-CD and chitosan)and consequently characterized by DLS,TEM,FT-IR,~1H NMR,SEM,etc.In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel(Cur-CS-CM-β-CD)released Cur rapidly under acidic conditions,and its cumulative release rate is 41%,56%and 67%at pH 7.4,6.5 and 5.5,respectively.The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay.The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is(50.2±2.5)%at 10μM,(98.3±1.2)%at 40μM and(97.5±1.2)%at 80μM,respectively.It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.展开更多
The pH-sensitive hydrogels play a crucial role in applications such as soft robotics,drug delivery,and biomedical sensors,as they require precise control of swelling behaviors and stress distributions.Traditional expe...The pH-sensitive hydrogels play a crucial role in applications such as soft robotics,drug delivery,and biomedical sensors,as they require precise control of swelling behaviors and stress distributions.Traditional experimental methods struggle to capture stress distributions due to technical limitations,while numerical approaches are often computationally intensive.This study presents a hybrid framework combining analytical modeling and machine learning(ML)to overcome these challenges.An analytical model is used to simulate transient swelling behaviors and stress distributions,and is confirmed to be viable through the comparison of the obtained simulation results with the existing experimental swelling data.The predictions from this model are used to train neural networks,including a two-step augmented architecture.The initial neural network predicts hydration values,which are then fed into a second network to predict stress distributions,effectively capturing nonlinear interdependencies.This approach achieves mean absolute errors(MAEs)as low as 0.031,with average errors of 1.9%for the radial stress and 2.55%for the hoop stress.This framework significantly enhances the predictive accuracy and reduces the computational complexity,offering actionable insights for optimizing hydrogel-based systems.展开更多
Chirality,ubiquitous in living matter,plays vital roles in a series of physiological processes.The clarification of the multiple functions of chirality in bioapplications may provide innovative methodologies for engin...Chirality,ubiquitous in living matter,plays vital roles in a series of physiological processes.The clarification of the multiple functions of chirality in bioapplications may provide innovative methodologies for engineering anti-tumor agents.Nevertheless,the related research has been rarely explored.In this study,the chiral supramolecular l/d-cysteine(Cys)-Zn^(2+)-indocyanine green(ICG)nanoparticles were constructed through the coordination interaction between l/d-Cys and Zn^(2+),followed by the encapsulation of ICG.Experimental findings revealed that the d-Cys-Zn^(2+)-ICG exhibited 17.31 times higher binding affinity toward phospholipid-composed liposomes compared to l-Cys-Zn^(2+)-ICG.Furthermore,driven by chiralityspecific interaction,a 2.07 folds greater cellular internalization of d-Cys-Zn^(2+)-ICG than l-Cys-Zn^(2+)-ICG was demonstrated.Additionally,the triple-level chirality-dependent photothermal,photodynamic and Zn^(2+)releasing anti-tumor effects of l/d Cys-Zn^(2+)-ICG in vitro were verified.As a result,the d-formed nanoparticles achieved 1.93 times higher anti-tumor efficiency than the l-formed ones.The triple-level chirality-mediated anti-tumor effect highlighted in this study underscores the enormous potential of chirality in biomedicine and holds substantial significance in improving cancer therapeutic efficacy.展开更多
An active protection coating for pH-responsive was prepared.The hollow mesoporous silica microspheres(HMSNs)were loaded with 2-mercaptobenzothiazole(MBT),and then they were coated with chitosan(CS).The composite micro...An active protection coating for pH-responsive was prepared.The hollow mesoporous silica microspheres(HMSNs)were loaded with 2-mercaptobenzothiazole(MBT),and then they were coated with chitosan(CS).The composite microspheres were in the range of 650−750 nm in diameter.CS-HMSN-MBT coating had a faster repair rate under acidic conditions by synergistic effect between CS and MBT.The repair rate under alkaline conditions was slowed down.The active protection performance reached the strongest after 3 d immersion.The corrosion inhibitor release mechanism was optimized to extend the service life of the coating and to achieve long-term service of the copper substrate.展开更多
The combination of nucleic acid and small-molecule drugs in tumor treatment holds significant promise;however,the precise delivery and controlled release of drugs within the cytoplasm encounter substantial obstacles,i...The combination of nucleic acid and small-molecule drugs in tumor treatment holds significant promise;however,the precise delivery and controlled release of drugs within the cytoplasm encounter substantial obstacles,impeding the advancement of formulations.To surmount the challenges associated with precise drug delivery and controlled release,we have developed a multi-level p H-responsive co-loaded drug lipid nanoplatform.This platform first employs cyclic cell-penetrating peptides to exert a multi-level pH response,thereby enhancing the uptake efficiency of tumor cells and endow the nanosystem with effective endosomal/lysosomal escape.Subsequently,small interferring RNA(siRNA)complexes are formed by compacting siRNA with stearic acid octahistidine,which is capable of responding to the lysosome-tocytoplasm pH gradient and facilitate siRNA release.The siRNA complexes and docetaxel are simultaneously encapsulated into liposomes,thereby creating a lipid nanoplatform capable of co-delivering nucleic acid and small-molecule drugs.The efficacy of this platform has been validated through both in vitro and in vivo experiments,affirming its significant potential for practical applications in the co-delivery of nucleic acids and small-molecule drugs.展开更多
The utilization of fungicides in plants is very low,emphasizing the need to improve their utilization rates.In this study,the fungicide dimethachlon(Dim)was encapsulated within hollow mesoporous silica(HMSNs),and a co...The utilization of fungicides in plants is very low,emphasizing the need to improve their utilization rates.In this study,the fungicide dimethachlon(Dim)was encapsulated within hollow mesoporous silica(HMSNs),and a coating was formed on the HMSNs surface through the reaction of Na_(2)CO_(3)and CaCl_(2),resulting in a pH-responsive delivery system named D/H@CaCO_(3),proven valuable in preventing sclerotinia diseases in romaine lettuce.When disease-infested romaine lettuce was treated with D/H@CaCO_(3),it degraded in the acidic microenvironment of Sclerotinia sclerotiorum(S.sclerotiorum),allowing for the p H-responsive release of Dim and effectively killing S.sclerotiorum.Moreover,the degraded CaC O_(3)coating releases CO_(2),which enhances the photosynthetic pigment contents,such as chlorophyll a,chlorophyll b,and carotenoids,in turn promoting plant growth.D/H@CaCO_(3)is biologically safe for plants and is environmentally friendly,as confirmed by assessments involving zebrafish and earthworms.Given their antifungal capabilities,the controlled release of fungicides offers potential for plant protection.展开更多
In this paper,tannic acid(TA)and Fe~(3+)were added to form a layer of metal-polyphenol network structure on the surface of the nanoparticles which were fabricated by zein and carbon quantum dots(CQDs)encapsulating phl...In this paper,tannic acid(TA)and Fe~(3+)were added to form a layer of metal-polyphenol network structure on the surface of the nanoparticles which were fabricated by zein and carbon quantum dots(CQDs)encapsulating phlorotannins(PTN).pH-Responsive nanoparticles were prepared successfully(zein-PTN-CQDs-Fe-~Ⅲ).Further,the formation of composite nanoparticles was confirmed by a series of characterization methods.The zeta-potential and Fourier transform infrared spectroscopy data proved that electrostatic interaction and hydrogen bonding are dominant forces to form nanoparticles.The encapsulation efficiency(EE)revealed that metal-polyphenol network structure could improve the EE of PTN.Thermogravimetric analysis and differential scanning calorimetry experiment indicated the thermal stability of zein-PTN-CQDs-Fe~Ⅲnanoparticles increased because of metal-polyphenol network structure.The pH-responsive nanoparticles greatly increased the release rate of active substances and achieved targeted release.展开更多
The clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9(CRISPR/Cas9)system is an RNA-guided platform for highly efficient and specific genome targeting in diverse organisms,which has...The clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9(CRISPR/Cas9)system is an RNA-guided platform for highly efficient and specific genome targeting in diverse organisms,which has been exploited for various applications in gene manipulation.Compared with the constantly active CRISPR/Cas9 function,conditional control of its activity can improve the performance of the system with reduced side effects and high spatiotemporal precision.The pH-responsive triplex RNA was successful used in CRISPR-derived RNA/trans-activating crRNA(crRNA/tracrRNA)of CRISPR/Cas9,thus affecting RNA/dead Cas9(dCas9)complex to target DNA in vitro and in vivo.This design of triplex RNA opens a new window towards the broad involvement of eukaryotic cells for conditional control of CRISPR/Cas9function.?2024 Published by Elsevier B.V.on behalf of Chinese Chemical Society and Institute of Materia Medica,Chinese Academy of Medical Sciences.展开更多
Due to the various pH liquid environment in nature,the pH-responsive lubricating hydrogel is widely investigated and developed for tissue interface substitute.However,the applied liquid environment will lead to poor m...Due to the various pH liquid environment in nature,the pH-responsive lubricating hydrogel is widely investigated and developed for tissue interface substitute.However,the applied liquid environment will lead to poor mechanical property and weaken the pH-responsive capability.In this work,a carbon dotsenhanced pH-responsive lubricating hydrogel is developed by combining a pH-responsive section of dynamic PVA-borax network into a PAAm covalent polymer network.The formed hydrogel presents a partial gel-sol transition under controlled pH environments.At low pH environments(<6.0),the formed lubricating layer originated from dynamic disassembly of PVA-borax hydrogel,and brings the lubricating properties on the hydrogel surface.Moreover,the mechanical strength and lubrication properties are well promoted by introducing the carbon dots into the hydrogel,the blue sol layer can be observed more visually under the fluorescence microscope.The pH-response also exhibits well reversibility.The prepared hydrogel broadens the idea for designing pH-responsive soft materials for soft lubricating actuator or robot.展开更多
Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural bones.However,the inherent bioinertness of pristi...Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural bones.However,the inherent bioinertness of pristine PEEK results in insufficient osseointegration.Moreover,implant-associated infection(IAI)has become a serious threat in orthopedic surgery.These risks usually lead to implant loosening,delayed healing,and even the failure of implantation,hampering many clinical applications of PEEK.In this study,we present a facile strategy to endow PEEK implants with enhanced osseointegration and pH-responsive antibacterial activity.Briefly,pristine PEEK was first treated with mixed acids to obtain a porous structure(referred to as SNPEEK),and then the metal-phenolic networks(MPN)coating was prepared using layer-by-layer(LbL)assembly consisting of Sr^(2+) and tannin acid(TA)(referred to as ST coating).The results demonstrated that the dual-functional PEEK displayed enhanced antibacterial activity in pH-responsive manner.At pH 7.4,the antibacterial ratios were 71.72%and 66.79%against Staphylococcus aureus(MSSA,ATCC 25,923)and methicillin-resistant Staphylococcus aureus(MRSA,ATCC BAA-40),respectively.Remarkably,at pH 5.5,the antibacterial activities significantly increased,resulting in killing ratios of 99.98%and 100%,respectively.Furthermore,the dual-functional PEEK promoted osteogenic differentiation of pre-osteoblasts(MC3T3-E1)and migration of human umbilical vascular endothelial cells(HUVECs).In addition,the dual-functional PEEK demonstrated effective anti-infection ability and desirable new bone formation ability in vivo compared to both pristine PEEK and SNPEEK implants.Overall,this study provides a promising strategy to endow PEEK implants with effective osseointegration and anti-infective ability,representing a prospective solution to address current clinical challenges associated with PEEK implants.展开更多
To realize single-stimulus-induced simultaneous multi-behaviors in hydrogels is still quite challenging nowadays.Herein,an intelli gent pH-responsive hydrogel(BP4VA/PAS)with rapid and high contrast changes in color,fl...To realize single-stimulus-induced simultaneous multi-behaviors in hydrogels is still quite challenging nowadays.Herein,an intelli gent pH-responsive hydrogel(BP4VA/PAS)with rapid and high contrast changes in color,fluorescence,and shape simultaneously is reported The BP4VA/PAS hydrogel is fabricated by incorporating styryl anthracene derivative(BP4VA)into copolymer networks(PAS)of acrylamide and sodium 4-styrene sulfonate.Under acid conditions,the protonation of BP4VA generates a rapid change with high color contrast from yellow to red and a fluorescence switch between bright green and weak red emission.At the same time,the electrostatic interactions between 2H-BP4VA^(2+)and sulfonate anions suspended on PAS trigger BP4VA/PAS hydrogels to shrink.Upon alkaline treatment,the 2H-BP4VA^(2+)/PAS hydrogel deproto nates and recovers to its original color,fluorescence,and shape.Furthermore,utilizing rapid and remarkable pH-responsive properties o BP4VA/PAS hydrogels,we successfully demonstrated its applications in biomimicry,camouflage,and multistage information encryption.Collec tively,this work provided an elegant strategy to develop intelligent hydrogels in applications of biomimetic smart materials and information en cryption.展开更多
Manganese oxide hollow spheres were prepared by a novel and facile approach using pH- responsive microgels as templates. The final products were thoroughly characterized with X-ray powder diffraction, thermogravimetri...Manganese oxide hollow spheres were prepared by a novel and facile approach using pH- responsive microgels as templates. The final products were thoroughly characterized with X-ray powder diffraction, thermogravimetric analysis, scanning electron microscopy, Fourier transform infrared, and transmission electron microscopy. The results reveal that the shell thickness of manganese oxide hollow spheres increased with the dosage of KMnO4, which implies that a controllable and feasible strategy for manganese oxide hollow spheres prepa- ration has been established. Further studies on the microgels template showed some of them had an irreversible swelling/deswelling transition due to the uneven cross-link extent. Based on the results, a probable formation mechanism for the hollow spheres was proposed.展开更多
In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a func...In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.展开更多
Developing methods for efficient product/catalyst separation and catalyst recycling is meaningful in multi-phase catalytic reactions. Here, we reported a p H-responsive emulsion system stabilized by interfacially acti...Developing methods for efficient product/catalyst separation and catalyst recycling is meaningful in multi-phase catalytic reactions. Here, we reported a p H-responsive emulsion system stabilized by interfacially active TiO2 nanoparticles for achieving in situ product/catalyst separation and catalyst recycling. In this system, emulsification and demulsification process could be easily engineered through tuning the p H values. The emulsion droplets were destroyed completely at a p H value of 3–4, and the solid catalyst distributed in the aqueous phase could be used to the next reaction cycle after removal of the organic product and adjusting the p H to 7–8. Such a p H triggered switchable Pickering emulsion catalytic system not only shows good recyclability of the solid catalyst but also high catalytic efficiency,and could be recycled more than 10 cycles.展开更多
Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feas...Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.展开更多
Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenge...Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges.To this end,we developed a cRGD-decorated pH-responsive polyion complex(PIC)micelle for intracellular targeted delivery of doxorubicin(DOX)to upregulate tumor inhibition and reduce toxicity.The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine)and the anionic acid-sensitive 2,3-dimethylmaleic anhydride-modified doxorubicin(DAD).The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition ofαvβ3 integrin on the membrane of tumor cells.The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD.Moreover,the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls.The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.展开更多
A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chr...A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.展开更多
The novel quaternized hydroxypropyl cellulose-g-poly(THF-co-epichlorohydrin)graft copolymers,HPC-g-QCP(THF-co-ECH),have been successfully synthesized to combine the properties from hydrophilic hard HPC biomacromolecul...The novel quaternized hydroxypropyl cellulose-g-poly(THF-co-epichlorohydrin)graft copolymers,HPC-g-QCP(THF-co-ECH),have been successfully synthesized to combine the properties from hydrophilic hard HPC biomacromolecular backbone and hydrophobic flexible polyether branches.Firstly,the P(THF-co-ECH)living chains were synthesized by cationic ring-opening copolymerization of THF with ECH.Secondly,P(THF-co-ECH)living chains were grafted onto HPC backbone by reaction with-OH groups along HPC to produce HPC-g-P(THF-co-ECH)graft copolymers.Thirdly,the mentioned graft copolymers were quaternized by reaction with ternanyamine to generate functionalized HPC-g-QCP(THF-co-ECH).The HPC-g-QCP(THF-co-ECH)graft copolymers exhibited good antibacterial ability against S.aureus or E.coli bacteria.The ibuprofen(IBU)-loaded microparticles of HPC-g-(QC)P(THF-co-ECH)graft copolymers were prepared by electrospraying.The in vitro pH-responsive drug-release behavior of IBU reached up to 75%of drug-loaded at pH=7A.This quaternized graft copolymer was beneficial to solving the problems of a burst effect and fast release of HPC as drug carriers.展开更多
Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-resp...Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor(VEGF)that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release.The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles(AgNPs)in situ,and dynamically crosslink with the polyacrylamide,which forms a stable slow-release system with different release behavior for the VEGF and AgNPs.The hydrogel inhib-ited bacterial formation and accelerated wound healing.With the hydrogel dressing,83.3%±4.29%of the wound heals at day 7,which is 40.9%±8.5%higher than the non-treatment group in defect infected model.The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines,and the release of VEGF in the middle and late phases of wound healing in response to pH changes pro-motes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine.The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microen-vironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases.Collectively,the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.展开更多
文摘Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.
基金Funded by the Tianjin Municipal Education Commission(No.2022ZD041)。
文摘We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepared(by CM-β-CD and chitosan)and consequently characterized by DLS,TEM,FT-IR,~1H NMR,SEM,etc.In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel(Cur-CS-CM-β-CD)released Cur rapidly under acidic conditions,and its cumulative release rate is 41%,56%and 67%at pH 7.4,6.5 and 5.5,respectively.The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay.The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is(50.2±2.5)%at 10μM,(98.3±1.2)%at 40μM and(97.5±1.2)%at 80μM,respectively.It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.
文摘The pH-sensitive hydrogels play a crucial role in applications such as soft robotics,drug delivery,and biomedical sensors,as they require precise control of swelling behaviors and stress distributions.Traditional experimental methods struggle to capture stress distributions due to technical limitations,while numerical approaches are often computationally intensive.This study presents a hybrid framework combining analytical modeling and machine learning(ML)to overcome these challenges.An analytical model is used to simulate transient swelling behaviors and stress distributions,and is confirmed to be viable through the comparison of the obtained simulation results with the existing experimental swelling data.The predictions from this model are used to train neural networks,including a two-step augmented architecture.The initial neural network predicts hydration values,which are then fed into a second network to predict stress distributions,effectively capturing nonlinear interdependencies.This approach achieves mean absolute errors(MAEs)as low as 0.031,with average errors of 1.9%for the radial stress and 2.55%for the hoop stress.This framework significantly enhances the predictive accuracy and reduces the computational complexity,offering actionable insights for optimizing hydrogel-based systems.
基金supported by the National Natural Science Foundation of China(Nos.22002138,22372144,22272146,21922202)the Chinese Postdoctoral Science Foundation(No.2021M692714)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Chirality,ubiquitous in living matter,plays vital roles in a series of physiological processes.The clarification of the multiple functions of chirality in bioapplications may provide innovative methodologies for engineering anti-tumor agents.Nevertheless,the related research has been rarely explored.In this study,the chiral supramolecular l/d-cysteine(Cys)-Zn^(2+)-indocyanine green(ICG)nanoparticles were constructed through the coordination interaction between l/d-Cys and Zn^(2+),followed by the encapsulation of ICG.Experimental findings revealed that the d-Cys-Zn^(2+)-ICG exhibited 17.31 times higher binding affinity toward phospholipid-composed liposomes compared to l-Cys-Zn^(2+)-ICG.Furthermore,driven by chiralityspecific interaction,a 2.07 folds greater cellular internalization of d-Cys-Zn^(2+)-ICG than l-Cys-Zn^(2+)-ICG was demonstrated.Additionally,the triple-level chirality-dependent photothermal,photodynamic and Zn^(2+)releasing anti-tumor effects of l/d Cys-Zn^(2+)-ICG in vitro were verified.As a result,the d-formed nanoparticles achieved 1.93 times higher anti-tumor efficiency than the l-formed ones.The triple-level chirality-mediated anti-tumor effect highlighted in this study underscores the enormous potential of chirality in biomedicine and holds substantial significance in improving cancer therapeutic efficacy.
基金Project(2023YFC2907304)supported by the National Key R&D Program Projects,ChinaProject(ZR2021ME087)supported by the Natural Science Foundation of Shandong Province,China+1 种基金Project(2022KLMM305)supported by the Shandong Provincial Key Laboratory of Mining Machinery Engineering School Enterprise Joint Fund,ChinaProject(2023CXPT062)supported by the Shandong Key Research and Development Program(Competitive Innovation Platform),China。
文摘An active protection coating for pH-responsive was prepared.The hollow mesoporous silica microspheres(HMSNs)were loaded with 2-mercaptobenzothiazole(MBT),and then they were coated with chitosan(CS).The composite microspheres were in the range of 650−750 nm in diameter.CS-HMSN-MBT coating had a faster repair rate under acidic conditions by synergistic effect between CS and MBT.The repair rate under alkaline conditions was slowed down.The active protection performance reached the strongest after 3 d immersion.The corrosion inhibitor release mechanism was optimized to extend the service life of the coating and to achieve long-term service of the copper substrate.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81973251 and 81302725)Hebei Province Funding Project for Introduced Overseas Personnel(Nos.C20230351 and C20220345)+3 种基金Key Research and Development Program of Hebei Province(No.22372701D)Hebei Province Natural Science Fund(No.H2020206610)Hebei Provincial Health Commission Government-Funded Clinical Medicine Talent Program(No.ZF2024048)Hebei Medical University Undergraduate Innovative Experiment Program(No.USIP2023008)。
文摘The combination of nucleic acid and small-molecule drugs in tumor treatment holds significant promise;however,the precise delivery and controlled release of drugs within the cytoplasm encounter substantial obstacles,impeding the advancement of formulations.To surmount the challenges associated with precise drug delivery and controlled release,we have developed a multi-level p H-responsive co-loaded drug lipid nanoplatform.This platform first employs cyclic cell-penetrating peptides to exert a multi-level pH response,thereby enhancing the uptake efficiency of tumor cells and endow the nanosystem with effective endosomal/lysosomal escape.Subsequently,small interferring RNA(siRNA)complexes are formed by compacting siRNA with stearic acid octahistidine,which is capable of responding to the lysosome-tocytoplasm pH gradient and facilitate siRNA release.The siRNA complexes and docetaxel are simultaneously encapsulated into liposomes,thereby creating a lipid nanoplatform capable of co-delivering nucleic acid and small-molecule drugs.The efficacy of this platform has been validated through both in vitro and in vivo experiments,affirming its significant potential for practical applications in the co-delivery of nucleic acids and small-molecule drugs.
基金support of this research by National Key R&D Program of China(No.2022YFE0139800)National Natural Science Foundation of China(Nos.82272154,32201101)+7 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023-JKCS-12)Tianjin Science Fund for Distinguished Young Scholars(No.22JCJQJC00120)the Fundamental Research Funds for the Central Universities(Nos.2021-RC310–005,3332023069)Science and Technology Program of Tianjin City(the Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei Region,No.22JCZXJC00060)the Key Project of Basic Research of Shenzhen(No.JCYJ20200109113603854)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2021-I2M1–058,2022-I2M-2–003)the Central Government Guides Local Special Funds for Scientific and Technological Development(No.ZY20198002)Guilin Scientific Research and Technology Development Plan(No.20210227–3)。
文摘The utilization of fungicides in plants is very low,emphasizing the need to improve their utilization rates.In this study,the fungicide dimethachlon(Dim)was encapsulated within hollow mesoporous silica(HMSNs),and a coating was formed on the HMSNs surface through the reaction of Na_(2)CO_(3)and CaCl_(2),resulting in a pH-responsive delivery system named D/H@CaCO_(3),proven valuable in preventing sclerotinia diseases in romaine lettuce.When disease-infested romaine lettuce was treated with D/H@CaCO_(3),it degraded in the acidic microenvironment of Sclerotinia sclerotiorum(S.sclerotiorum),allowing for the p H-responsive release of Dim and effectively killing S.sclerotiorum.Moreover,the degraded CaC O_(3)coating releases CO_(2),which enhances the photosynthetic pigment contents,such as chlorophyll a,chlorophyll b,and carotenoids,in turn promoting plant growth.D/H@CaCO_(3)is biologically safe for plants and is environmentally friendly,as confirmed by assessments involving zebrafish and earthworms.Given their antifungal capabilities,the controlled release of fungicides offers potential for plant protection.
基金supported by the National Key R&D Program of China (2018YFD0901106)the Wenzhou Major Science and Technology Project (ZN2021002)the Ningbo“3315 series program”for high-level talents (2020B-34-G)。
文摘In this paper,tannic acid(TA)and Fe~(3+)were added to form a layer of metal-polyphenol network structure on the surface of the nanoparticles which were fabricated by zein and carbon quantum dots(CQDs)encapsulating phlorotannins(PTN).pH-Responsive nanoparticles were prepared successfully(zein-PTN-CQDs-Fe-~Ⅲ).Further,the formation of composite nanoparticles was confirmed by a series of characterization methods.The zeta-potential and Fourier transform infrared spectroscopy data proved that electrostatic interaction and hydrogen bonding are dominant forces to form nanoparticles.The encapsulation efficiency(EE)revealed that metal-polyphenol network structure could improve the EE of PTN.Thermogravimetric analysis and differential scanning calorimetry experiment indicated the thermal stability of zein-PTN-CQDs-Fe~Ⅲnanoparticles increased because of metal-polyphenol network structure.The pH-responsive nanoparticles greatly increased the release rate of active substances and achieved targeted release.
基金supported by the National Key R&D Program of China(Nos.2022YFC2804101,2020YFA0211200)National Natural Science Foundation of China(Nos.22377056,22222706,21977122)。
文摘The clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9(CRISPR/Cas9)system is an RNA-guided platform for highly efficient and specific genome targeting in diverse organisms,which has been exploited for various applications in gene manipulation.Compared with the constantly active CRISPR/Cas9 function,conditional control of its activity can improve the performance of the system with reduced side effects and high spatiotemporal precision.The pH-responsive triplex RNA was successful used in CRISPR-derived RNA/trans-activating crRNA(crRNA/tracrRNA)of CRISPR/Cas9,thus affecting RNA/dead Cas9(dCas9)complex to target DNA in vitro and in vivo.This design of triplex RNA opens a new window towards the broad involvement of eukaryotic cells for conditional control of CRISPR/Cas9function.?2024 Published by Elsevier B.V.on behalf of Chinese Chemical Society and Institute of Materia Medica,Chinese Academy of Medical Sciences.
基金supported by the National Natural Science Foundation of China(No.22175075).
文摘Due to the various pH liquid environment in nature,the pH-responsive lubricating hydrogel is widely investigated and developed for tissue interface substitute.However,the applied liquid environment will lead to poor mechanical property and weaken the pH-responsive capability.In this work,a carbon dotsenhanced pH-responsive lubricating hydrogel is developed by combining a pH-responsive section of dynamic PVA-borax network into a PAAm covalent polymer network.The formed hydrogel presents a partial gel-sol transition under controlled pH environments.At low pH environments(<6.0),the formed lubricating layer originated from dynamic disassembly of PVA-borax hydrogel,and brings the lubricating properties on the hydrogel surface.Moreover,the mechanical strength and lubrication properties are well promoted by introducing the carbon dots into the hydrogel,the blue sol layer can be observed more visually under the fluorescence microscope.The pH-response also exhibits well reversibility.The prepared hydrogel broadens the idea for designing pH-responsive soft materials for soft lubricating actuator or robot.
基金supported by the National Natu-ral Science Foundation of China(No.52073230)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32).
文摘Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural bones.However,the inherent bioinertness of pristine PEEK results in insufficient osseointegration.Moreover,implant-associated infection(IAI)has become a serious threat in orthopedic surgery.These risks usually lead to implant loosening,delayed healing,and even the failure of implantation,hampering many clinical applications of PEEK.In this study,we present a facile strategy to endow PEEK implants with enhanced osseointegration and pH-responsive antibacterial activity.Briefly,pristine PEEK was first treated with mixed acids to obtain a porous structure(referred to as SNPEEK),and then the metal-phenolic networks(MPN)coating was prepared using layer-by-layer(LbL)assembly consisting of Sr^(2+) and tannin acid(TA)(referred to as ST coating).The results demonstrated that the dual-functional PEEK displayed enhanced antibacterial activity in pH-responsive manner.At pH 7.4,the antibacterial ratios were 71.72%and 66.79%against Staphylococcus aureus(MSSA,ATCC 25,923)and methicillin-resistant Staphylococcus aureus(MRSA,ATCC BAA-40),respectively.Remarkably,at pH 5.5,the antibacterial activities significantly increased,resulting in killing ratios of 99.98%and 100%,respectively.Furthermore,the dual-functional PEEK promoted osteogenic differentiation of pre-osteoblasts(MC3T3-E1)and migration of human umbilical vascular endothelial cells(HUVECs).In addition,the dual-functional PEEK demonstrated effective anti-infection ability and desirable new bone formation ability in vivo compared to both pristine PEEK and SNPEEK implants.Overall,this study provides a promising strategy to endow PEEK implants with effective osseointegration and anti-infective ability,representing a prospective solution to address current clinical challenges associated with PEEK implants.
基金financially supported by the National Natural Science Foundation of China(Nos.51373025 and 22005021)Beijing Natural Science Foundation(No.2242044)+2 种基金the Fundamental Research Funds for the Central Universities(No.FRF-TP-22-003A1)China Postdoctoral Science Foundation(No.2023M730311)the Program for New Century Excellent Talents in University(No.NCET-11-0582)。
文摘To realize single-stimulus-induced simultaneous multi-behaviors in hydrogels is still quite challenging nowadays.Herein,an intelli gent pH-responsive hydrogel(BP4VA/PAS)with rapid and high contrast changes in color,fluorescence,and shape simultaneously is reported The BP4VA/PAS hydrogel is fabricated by incorporating styryl anthracene derivative(BP4VA)into copolymer networks(PAS)of acrylamide and sodium 4-styrene sulfonate.Under acid conditions,the protonation of BP4VA generates a rapid change with high color contrast from yellow to red and a fluorescence switch between bright green and weak red emission.At the same time,the electrostatic interactions between 2H-BP4VA^(2+)and sulfonate anions suspended on PAS trigger BP4VA/PAS hydrogels to shrink.Upon alkaline treatment,the 2H-BP4VA^(2+)/PAS hydrogel deproto nates and recovers to its original color,fluorescence,and shape.Furthermore,utilizing rapid and remarkable pH-responsive properties o BP4VA/PAS hydrogels,we successfully demonstrated its applications in biomimicry,camouflage,and multistage information encryption.Collec tively,this work provided an elegant strategy to develop intelligent hydrogels in applications of biomimetic smart materials and information en cryption.
文摘Manganese oxide hollow spheres were prepared by a novel and facile approach using pH- responsive microgels as templates. The final products were thoroughly characterized with X-ray powder diffraction, thermogravimetric analysis, scanning electron microscopy, Fourier transform infrared, and transmission electron microscopy. The results reveal that the shell thickness of manganese oxide hollow spheres increased with the dosage of KMnO4, which implies that a controllable and feasible strategy for manganese oxide hollow spheres prepa- ration has been established. Further studies on the microgels template showed some of them had an irreversible swelling/deswelling transition due to the uneven cross-link extent. Based on the results, a probable formation mechanism for the hollow spheres was proposed.
基金supported by the Chinese Natural Science Foundation Project (Grant No. 30970784 and 81171455)a National Distinguished Young Scholars Grant (Grant No. 31225009) from the National Natural Science Foundation of China+5 种基金the National Key Basic Research Program of China (Grant No. 2009CB930200)the Chinese Academy of Sciences (CAS) ‘Hundred Talents Program’ (Grant No. 07165111ZX)the CAS Knowledge Innovation Program, and the State HighTech Development Plan (Grant No. 2012AA020804)the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (Grant No. XDA09030301)NIH/NIMHD 8 G12 MD007597USAMRMC W81XWH-10-1-0767 grants
文摘In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.
基金the Natural Science Foundation of China (Nos. 21733009, 21573136, and U1510105)the Key Scientist and Technology Program of Shanxi Province (No. 20150313003-1)Shanxi Scholarship Council of China (No. 2015-003)
文摘Developing methods for efficient product/catalyst separation and catalyst recycling is meaningful in multi-phase catalytic reactions. Here, we reported a p H-responsive emulsion system stabilized by interfacially active TiO2 nanoparticles for achieving in situ product/catalyst separation and catalyst recycling. In this system, emulsification and demulsification process could be easily engineered through tuning the p H values. The emulsion droplets were destroyed completely at a p H value of 3–4, and the solid catalyst distributed in the aqueous phase could be used to the next reaction cycle after removal of the organic product and adjusting the p H to 7–8. Such a p H triggered switchable Pickering emulsion catalytic system not only shows good recyclability of the solid catalyst but also high catalytic efficiency,and could be recycled more than 10 cycles.
基金financially supported by the National Basic Research Program of China (No. 2015CB755500)the Natural Science Foundation of Guangdong Province (No. 2014A030312018)Science and Technology Planning Project of Guangdong Province (No. 2016A020215088)
文摘Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.51973216,51873207,51833010,51703225,51673190,51673187,51603204 and 51520105004)the Science and Technology Development Program of Jilin Province(No.20190201068JC)+2 种基金the National Key Research and Development Program of China(No.2016YFC1100701)the Youth Talents Promotion Project of Jilin Province(No.181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019005)。
文摘Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges.To this end,we developed a cRGD-decorated pH-responsive polyion complex(PIC)micelle for intracellular targeted delivery of doxorubicin(DOX)to upregulate tumor inhibition and reduce toxicity.The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine)and the anionic acid-sensitive 2,3-dimethylmaleic anhydride-modified doxorubicin(DAD).The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition ofαvβ3 integrin on the membrane of tumor cells.The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD.Moreover,the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls.The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.
基金supported by the Major National Scientific Research Projects (2015CB932103)
文摘A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21574007 and 51521062).
文摘The novel quaternized hydroxypropyl cellulose-g-poly(THF-co-epichlorohydrin)graft copolymers,HPC-g-QCP(THF-co-ECH),have been successfully synthesized to combine the properties from hydrophilic hard HPC biomacromolecular backbone and hydrophobic flexible polyether branches.Firstly,the P(THF-co-ECH)living chains were synthesized by cationic ring-opening copolymerization of THF with ECH.Secondly,P(THF-co-ECH)living chains were grafted onto HPC backbone by reaction with-OH groups along HPC to produce HPC-g-P(THF-co-ECH)graft copolymers.Thirdly,the mentioned graft copolymers were quaternized by reaction with ternanyamine to generate functionalized HPC-g-QCP(THF-co-ECH).The HPC-g-QCP(THF-co-ECH)graft copolymers exhibited good antibacterial ability against S.aureus or E.coli bacteria.The ibuprofen(IBU)-loaded microparticles of HPC-g-(QC)P(THF-co-ECH)graft copolymers were prepared by electrospraying.The in vitro pH-responsive drug-release behavior of IBU reached up to 75%of drug-loaded at pH=7A.This quaternized graft copolymer was beneficial to solving the problems of a burst effect and fast release of HPC as drug carriers.
文摘Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor(VEGF)that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release.The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles(AgNPs)in situ,and dynamically crosslink with the polyacrylamide,which forms a stable slow-release system with different release behavior for the VEGF and AgNPs.The hydrogel inhib-ited bacterial formation and accelerated wound healing.With the hydrogel dressing,83.3%±4.29%of the wound heals at day 7,which is 40.9%±8.5%higher than the non-treatment group in defect infected model.The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines,and the release of VEGF in the middle and late phases of wound healing in response to pH changes pro-motes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine.The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microen-vironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases.Collectively,the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.
