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
Responsive nanocontainers have dual functions in targeted delivery of corrosion inhibitors and emulsion development of shale oil in oil and gas fields,exhibiting potential for simultaneously achieving metal protection...Responsive nanocontainers have dual functions in targeted delivery of corrosion inhibitors and emulsion development of shale oil in oil and gas fields,exhibiting potential for simultaneously achieving metal protection and efficient oil and gas development from a material perspective.Here,we propose the preparation of a pH-responsive nanocontainer,HMSNs-g-PDEAEMA(poly[2-(N,N-diethyl amino)ethyl-methacrylate](PDEAEMA)grafted onto hollow mesoporous spherical silica(HMSNs)),to integrate the delivery of 2-mercaptobenzothiazole(MBT)for targeted corrosion inhibition and the emulsification of oil as Pickering emulsifiers.Under acidic conditions(reduced pH value caused by localized corrosion or high concentration acidic gases),PDEAEMA chains are protonated and extended by electrostatic repulsion,exposing pores on HMSNs surface and allowing the controlled release of loaded MBT molecules.Once transforming into a neutral or alkaline environment,the responsive release of the MBT process is inhibited.After the fluid passes through the wellbore and enters the shale layer,the HMSNs-g-PDEAEMA nanocontainers act as Pickering emulsifiers to achieve emulsification.The emulsified oil can be extracted onto the ground more efficiently,and a following pH-responsive demulsification process can be achieved.Overall,through a pH-responsive nanocontainer material,the dual function of corrosion inhibition and emulsification in oil and gas development is possible to be simultaneously achieved.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
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
Converting polyethylene terephthalate(PET)wastes to its monomer and valuable chemicals via ecofriendly chemical method is still a challenge task.Previously,phase transfer catalysts used for alkaline hydrolysis were so...Converting polyethylene terephthalate(PET)wastes to its monomer and valuable chemicals via ecofriendly chemical method is still a challenge task.Previously,phase transfer catalysts used for alkaline hydrolysis were soluble in reaction media and hardly separated after reaction.Here,we reported several pH-responsive catalysts combined alkyl quaternary ammonium units with heteropolyacid anion for achieving stepwise product/catalyst separation and catalyst recycling.The properties of homogeneous/heterogeneous transfer behavior allow catalyst to be easily separated from reaction media by adjusting of pH value.Among them,[C_(16)H_(33)N(CH_(3))_(3)]_(3)PW_(12)O_(40)(abbreviated as[CTA]_(3)PW)exhibits the highest activity and the most suitable pH responsive values.Such a pH triggered switchable catalytic system not only shows good performance for depolymerization of pure PET,but also some real PET wastes such as coloured trays and PE/PET complex films could be completely degraded into terephthalic acid.Additionally,the reaction kinetics and activation energy of PET alkaline hydrolysis also studied with and without pH-responsive[CTA]_(3)PW.展开更多
Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during c...Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.展开更多
PEGylated prodrug,covalent attaching polyethylene glycol(PEG) polymer chains to therapeutic drugs,is one of the most promising techniques to improve the water-solubility,stability,and therapeutic effect of drugs.In th...PEGylated prodrug,covalent attaching polyethylene glycol(PEG) polymer chains to therapeutic drugs,is one of the most promising techniques to improve the water-solubility,stability,and therapeutic effect of drugs.In this study,three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights,were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin(DOX).This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution.The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering(DLS) and transmission electron microscopy(TEM),re s pectively.It turned out that the nanoparticles could be kept stable in the physiological environment,but degraded in acidic medium.Subsequently,we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property.The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells,which have the potential for use in cancer therapy.展开更多
To improve the colloidal stability of bovine serum albumin （BSA） nanoparticles （hiPs） in diverse mediums, poly（allylamine hydrochloride） （PAH）/sodium poly（4-styrene sulfonate） （PSS） multilayers and poly（a...To improve the colloidal stability of bovine serum albumin （BSA） nanoparticles （hiPs） in diverse mediums, poly（allylamine hydrochloride） （PAH）/sodium poly（4-styrene sulfonate） （PSS） multilayers and poly（allylamine hydrochloride）-graft-poly（ethylene glycol） （PAH-g-PEG） coating were coated on the surface of BSA NPs. Stabilities of the BSA NPs in diverse mediums with different surfaces were detected by dynamic light scattering （DLS）. Multilayers and PAH-g-PEG coated BSA NPs can be well dispersed in various mediums with a narrow polydispersity index （PDI）. The BSA NPs with the highest surface density of PEG show the best stability. The multilayers and PAH-g-PEG coating do not deter the pH-dependent loading and release property of BSA NPs. At pH 9, the encapsulation efficiency of doxorubicin reaches almost 99%, and the release rate at pH 5.5 is significantly higher than that at pH 7.4.展开更多
pH-responsive micelles with a biodegradable PLA core and a mixed PEG/PDPA shell were prepared by self-assembly of poly（ethylene glycol）-b-poly（lactic acid） （PEG-b-PLA） and poly（2-（diisopropylamino）ethyl metha...pH-responsive micelles with a biodegradable PLA core and a mixed PEG/PDPA shell were prepared by self-assembly of poly（ethylene glycol）-b-poly（lactic acid） （PEG-b-PLA） and poly（2-（diisopropylamino）ethyl methacrylate）-b-poly（lactic acid） （PDPA-b- PLA）. The micellization status with different pH and the enzyme degradation behavior were characterized by IH-NMR spectroscopy, dynamic light scattering measurement and zeta potential test. The pH turning point of PDPA block was determined to be in the range of 5.5-7.0. While the pH was above 7.0, the PDPA block collapsed onto the PLA core and could protect the PLA core from invasion of enzyme, as a result, the micelle exhibited a resistance to the enzymatic degradation.展开更多
A supramolecular dimer of doxorubicin(DOX)was constructed via ternary host-vip interactions between cucurbit[8]uril(CB[8])and tryptophan modified DOX(DOX-Trp,connected with an acid-labile bond)and we demonstrate for...A supramolecular dimer of doxorubicin(DOX)was constructed via ternary host-vip interactions between cucurbit[8]uril(CB[8])and tryptophan modified DOX(DOX-Trp,connected with an acid-labile bond)and we demonstrate for the first time that a supramolecular dimer of DOX can be formed upon homo-dimerization by CB[8],which may act as a stimuli pH-responsive,supramolecular DOX dimer prodrug system.This supramolecular DOX dimer transported DOX efficiently and selectively to cancer cells,thereby exhibiting significantly minimized cytotoxicity against noncancerous cells while maintaining effective cytotoxicity against cancer cells.Under this strategy,many other anticancer drugs could be chemically modified and loaded as a dimeric"ammunition"into CB[8]as supramolecular dimer prodrug systems(or a"jet fighter")for improved cancer therapy.展开更多
Well-defined pH-responsive poly（e-caprolactone）-graft-β-cyclodextrin-graft-poly（2-（dimethylamino）ethyl- methacrylate）-co-poly（ethylene glycol） methacrylate amphiphilic copolymers （PCL-g-β-CD-g-P（DMAEMA-co-...Well-defined pH-responsive poly（e-caprolactone）-graft-β-cyclodextrin-graft-poly（2-（dimethylamino）ethyl- methacrylate）-co-poly（ethylene glycol） methacrylate amphiphilic copolymers （PCL-g-β-CD-g-P（DMAEMA-co-PEGMA）） were synthesized using a combination of atom transfer radical polymerization （ATRP）, ring opening polymerization （ROP） and ＂click＂ chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy （FTIR）, proton nuclear magnetic resonance （^1H-NMR）, and gel permeation chromatography （GPC）. Then, the polymers could self- assemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering （DLS） and transmission electron microscopy （TEM）. The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin （DOX） release, and these results revealed that the release rate of DOX could be effectively controlled by altering the pH, and the release of drug loading efficiency （DLE） was up to 88% （W/W）. CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy （CLSM） images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.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.
基金financially supported by the National Natu-ral Science Foundation of China(Nos.52204066 and 52474020)the Shandong Province Youth Entrepreneurship Technology Sup-port Program for Higher Education Institutions(No.2023KJ060)the Fundamental Research Funds for the Central Universities(No.23CX06018A).
文摘Responsive nanocontainers have dual functions in targeted delivery of corrosion inhibitors and emulsion development of shale oil in oil and gas fields,exhibiting potential for simultaneously achieving metal protection and efficient oil and gas development from a material perspective.Here,we propose the preparation of a pH-responsive nanocontainer,HMSNs-g-PDEAEMA(poly[2-(N,N-diethyl amino)ethyl-methacrylate](PDEAEMA)grafted onto hollow mesoporous spherical silica(HMSNs)),to integrate the delivery of 2-mercaptobenzothiazole(MBT)for targeted corrosion inhibition and the emulsification of oil as Pickering emulsifiers.Under acidic conditions(reduced pH value caused by localized corrosion or high concentration acidic gases),PDEAEMA chains are protonated and extended by electrostatic repulsion,exposing pores on HMSNs surface and allowing the controlled release of loaded MBT molecules.Once transforming into a neutral or alkaline environment,the responsive release of the MBT process is inhibited.After the fluid passes through the wellbore and enters the shale layer,the HMSNs-g-PDEAEMA nanocontainers act as Pickering emulsifiers to achieve emulsification.The emulsified oil can be extracted onto the ground more efficiently,and a following pH-responsive demulsification process can be achieved.Overall,through a pH-responsive nanocontainer material,the dual function of corrosion inhibition and emulsification in oil and gas development is possible to be simultaneously achieved.
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.
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.
基金the support of the National Natural Science Foundation of China(22005276)。
文摘Converting polyethylene terephthalate(PET)wastes to its monomer and valuable chemicals via ecofriendly chemical method is still a challenge task.Previously,phase transfer catalysts used for alkaline hydrolysis were soluble in reaction media and hardly separated after reaction.Here,we reported several pH-responsive catalysts combined alkyl quaternary ammonium units with heteropolyacid anion for achieving stepwise product/catalyst separation and catalyst recycling.The properties of homogeneous/heterogeneous transfer behavior allow catalyst to be easily separated from reaction media by adjusting of pH value.Among them,[C_(16)H_(33)N(CH_(3))_(3)]_(3)PW_(12)O_(40)(abbreviated as[CTA]_(3)PW)exhibits the highest activity and the most suitable pH responsive values.Such a pH triggered switchable catalytic system not only shows good performance for depolymerization of pure PET,but also some real PET wastes such as coloured trays and PE/PET complex films could be completely degraded into terephthalic acid.Additionally,the reaction kinetics and activation energy of PET alkaline hydrolysis also studied with and without pH-responsive[CTA]_(3)PW.
基金partially supported by the National Natural Science Foundation of China(51802209,22077093,51761145041,51525203)the National Research Programs from Ministry of Science and Technology(MOST)of China(2016YFA0201200)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20180848)the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technologythe 111 Program from the Ministry of Education of China.
文摘Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.
基金the financial supports from the National Natural Science Foundation of China(No.21374066)the Major Program of the Natural Science Project of Jiangsu Higher Education Institutions(No.15KJA150007)+2 种基金Natural Science Foundation of Jiangsu Province(No.BK20171212)the Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education InstitutionsSoochow-Waterloo University Joint Project for Nanotechnology from Suzhou Industrial Park
文摘PEGylated prodrug,covalent attaching polyethylene glycol(PEG) polymer chains to therapeutic drugs,is one of the most promising techniques to improve the water-solubility,stability,and therapeutic effect of drugs.In this study,three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights,were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin(DOX).This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution.The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering(DLS) and transmission electron microscopy(TEM),re s pectively.It turned out that the nanoparticles could be kept stable in the physiological environment,but degraded in acidic medium.Subsequently,we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property.The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells,which have the potential for use in cancer therapy.
基金financially supported by the Zhejiang Provincial Natural Science Foundation of China(Nos.Z4090177 and Y4110064)the Ministry of Science and Technology of China for the Indo-China Cooperation(No.2010DFA51510)the National Natural Science Foundation of China(Nos.51120135001 and 21174130)
文摘To improve the colloidal stability of bovine serum albumin （BSA） nanoparticles （hiPs） in diverse mediums, poly（allylamine hydrochloride） （PAH）/sodium poly（4-styrene sulfonate） （PSS） multilayers and poly（allylamine hydrochloride）-graft-poly（ethylene glycol） （PAH-g-PEG） coating were coated on the surface of BSA NPs. Stabilities of the BSA NPs in diverse mediums with different surfaces were detected by dynamic light scattering （DLS）. Multilayers and PAH-g-PEG coated BSA NPs can be well dispersed in various mediums with a narrow polydispersity index （PDI）. The BSA NPs with the highest surface density of PEG show the best stability. The multilayers and PAH-g-PEG coating do not deter the pH-dependent loading and release property of BSA NPs. At pH 9, the encapsulation efficiency of doxorubicin reaches almost 99%, and the release rate at pH 5.5 is significantly higher than that at pH 7.4.
基金supports by the National Natural Science Foundation of China (Nos. 21404082 and 51503104)the State Key Laboratory of Medicinal Chemical Biology of China (No. 201603001)Natural Science Foundation of Tianjin (Nos. 15JCQNJC05900, 15JCQNJC13400 and 16JCQNJC03000)
文摘pH-responsive micelles with a biodegradable PLA core and a mixed PEG/PDPA shell were prepared by self-assembly of poly（ethylene glycol）-b-poly（lactic acid） （PEG-b-PLA） and poly（2-（diisopropylamino）ethyl methacrylate）-b-poly（lactic acid） （PDPA-b- PLA）. The micellization status with different pH and the enzyme degradation behavior were characterized by IH-NMR spectroscopy, dynamic light scattering measurement and zeta potential test. The pH turning point of PDPA block was determined to be in the range of 5.5-7.0. While the pH was above 7.0, the PDPA block collapsed onto the PLA core and could protect the PLA core from invasion of enzyme, as a result, the micelle exhibited a resistance to the enzymatic degradation.
基金supported by the Science and Technology Development Fund,Macao SAR(No.030/2017/A1)University of Macao(No.MYRG2016-00008-ICMS-QRCM)the National Natural Science Foundation of China(No.21871301)。
文摘A supramolecular dimer of doxorubicin(DOX)was constructed via ternary host-vip interactions between cucurbit[8]uril(CB[8])and tryptophan modified DOX(DOX-Trp,connected with an acid-labile bond)and we demonstrate for the first time that a supramolecular dimer of DOX can be formed upon homo-dimerization by CB[8],which may act as a stimuli pH-responsive,supramolecular DOX dimer prodrug system.This supramolecular DOX dimer transported DOX efficiently and selectively to cancer cells,thereby exhibiting significantly minimized cytotoxicity against noncancerous cells while maintaining effective cytotoxicity against cancer cells.Under this strategy,many other anticancer drugs could be chemically modified and loaded as a dimeric"ammunition"into CB[8]as supramolecular dimer prodrug systems(or a"jet fighter")for improved cancer therapy.
基金financially supported by the National Natural Science Foundation of China(No.21367022)Bingtuan Innovation Team in Key Areas(No.2015BD003)
文摘Well-defined pH-responsive poly（e-caprolactone）-graft-β-cyclodextrin-graft-poly（2-（dimethylamino）ethyl- methacrylate）-co-poly（ethylene glycol） methacrylate amphiphilic copolymers （PCL-g-β-CD-g-P（DMAEMA-co-PEGMA）） were synthesized using a combination of atom transfer radical polymerization （ATRP）, ring opening polymerization （ROP） and ＂click＂ chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy （FTIR）, proton nuclear magnetic resonance （^1H-NMR）, and gel permeation chromatography （GPC）. Then, the polymers could self- assemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering （DLS） and transmission electron microscopy （TEM）. The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin （DOX） release, and these results revealed that the release rate of DOX could be effectively controlled by altering the pH, and the release of drug loading efficiency （DLE） was up to 88% （W/W）. CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy （CLSM） images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.
