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POLYMER INTERNATIONAL · 2015 ·Vol. 64 ·期 10 ·1415-1424 · IF 2.409

Temperature and pH responsive hydrogels based on polyethylene glycol analogues and poly(methacrylic acid) via click chemistry

Weijuan Sheng,Teng Liu,Shouxin Liu,Qinqin Wang,Xuan Li,Naer Guang

A novel temperature responsive copolymer, poly[2-(2-methoxyethoxy)ethyl methacrylate- co -oligo(ethylene glycol)methacrylate- co-N -hydroxymethyl acrylamide] [P(MEO 2 MA- co -OEGMA- co -HMAM)], was synthesized by atom transfer radical polymerization. pH responsive poly(methacrylic acid) (PMAA) was synthesized by reversible addition-fragmentation chain transfer polymerization. After the hydroxyl groups on P(MEO 2 MA- co -OEGMA- co -HMAM) were transformed into azide groups and the carboxyl groups on PMAA were transformed into alkyne groups respectively, a novel temperature and pH responsive hydrogel was fabricated by click chemistry between the azide-P(MEO 2 MA- co -OEGMA- co -HMAM) and alkyne-PMAA in the presence of CuSO 4 and sodium ascorbate in aqueous solution. The rheological kinetics of gel formation demonstrated that gelation had commenced within 5 min at 25 °C, since then the storage modulus ( G ′) was higher than the loss modulus ( G ″). SEM images of hydrogel morphology and the swelling ratios of hydrogel at different temperatures and pH proved that the formed hydrogel had temperature and pH sensitivities. Bovine serum albumin was used as a model to evaluate the sustained release of the hydrogel; the results indicated that the hydrogel was a promising candidate for controlling protein drug delivery. © 2015 Society of Chemical Industry

CAS / MDL: 134-03-2
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Journal of Materials Chemistry B · 2014 ·Vol. 3 ·期 7 ·1426-1432 · IF 0

pH- and redox-triggered synergistic controlled release of a ZnO-gated hollow mesoporous silica drug delivery system

Shanshan Wu,Xuan Huang,Xuezhong Du

Hollow mesoporous silica spheres (HMSS) have a hierarchical mesoporous structure composed of a hollow cavity and mesoporous shell available for high capacity drug storage. The covalent attachment of ZnO quantum dots (QDs) to the HMSS outer surface as gatekeepers via disulfide-conjugated two amide linkages encapsulated the anticancer drugs doxorubicin (DOX) within the HMSS cavities and pores, and minimized premature release of the drug. The controlled release of the drug from the ZnO-gated HMSS delivery system was realized by the dissolution of ZnO QDs upon a decrease in pH and cleavage of the disulfide bonds, which indicates that the pH- and redox-responsive controlled release of the drugs could be synergically stimulated by tumor cells with weakly acidic environments and high-expressed glutathione. The constructed ZnO-gated HMSS delivery system has promising applications in site-specific drug release for tumor chemotherapy.

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ANALYTICAL CHEMISTRY · 2015 · IF 5.636

Pattern Recognition of Monosaccharides via a Virtual Lectin Array Constructed by Boronate Affinity-Based pH-Featured Encoding

Xiaodong Bi,Daojin Li,Zhen Liu

Lectin array is an important tool in the fields of carbohydrate chemistry, glycobiology, and glycomics. Because natural lectins are associated with some apparent disadvantages such as tedious purification and easy loss of activity, artificial materials are applied to overcome such shortages by mimicking and replacing lectins in an artificial lectin array, among which boronate affinity-based materials are very outstanding and widely used. However, complicated synthetic works are often involved to design and create boronate affinity-based lectin-mimics. In this work, a facile and novel method was proposed to establish a virtual lectin array based on boronate affinity-based pH-featured encoding for discrimination of monosaccharides by pattern recognition. The dependence of boronate affinity on environmental pH was selected to encode each monosaccharide for feature generation, and the pH-featured encoding was used to construct the virtual lectin array. On the basis of the virtual array, pattern recognition algorithms were applied for data analysis. Monosaccharides were discriminated by principal component analysis, and the relations in the virtual lectin array were unraveled by cluster analysis. In this proof-of-concept work, without complicated synthesis or preparation, the proposed method was successful in mimicking lectin array and discriminating nine elementary monosaccharides found in nature, and it was also a new way of encoding in expanding the applications of boronate affinity-based materials and methods in the field of biomimetics.

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DALTON TRANSACTIONS · 2014 ·Vol. 43 ·期 48 ·18056-18065 · IF 4.097

P(EO-co-LLA) functionalized Fe3O4@mSiO2 nanocomposites for thermo/pH responsive drug controlled release and hyperthermia

Wei Guo,Chunyu Yang,Huiming Lin,Fengyu Qu

The Fe3O4@mSiO2 nanocarrier that consisted of a magnetic Fe3O4 nanoparticle core and a mesoporous silica (mSiO2) shell was synthesized. It shows a uniform sphere morphology about 65 nm in diameter. Considering the magnetic hyperthermia of Fe3O4 under an alternating magnetic field (AMF), a thermo-sensitive polymer, poly[(ethylene glycol)-co-(L-lactide)] (P(EO-co-LLA)), was used as “gatekeeper” coating outside Fe3O4@mSiO2 to regulate the drug release behavior. The design of the nanocarrier was expected to block off the pores at low temperature and to reopen them at high temperature reversibly. The obtained hybrid nanocomposites were capable of loading the anti-cancer drug doxorubicin (DOX) and controlled drug release behavior trigged by the hyperthermia of Fe3O4 under AMF. Besides, the nanocarriers also show pH-sensitive drug release based on the slight differences between the tumor (weakly acid) and the normal tissue (weakly alkaline). What's more, the chemotherapy of DOX combined with magnetic hyperthermia can improve the cytotoxicity obviously. On the basis of the high stability and excellent controlled release performance, the multifunctional nanocarriers exhibit potential applications in targeted-control drug release and hyperthermia for cancer treatment.

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RSC Advances · 2015 ·Vol. 5 ·期 36 ·28060-28069 · IF 3.84

pH/redox dual-sensitive nanoparticles based on the PCL/PEG triblock copolymer for enhanced intracellular doxorubicin release

Yan Cao,Junqiang Zhao,Yumin Zhang,Jianfeng Liu,Jinjian Liu,Anjie Dong,Liandong Deng

pH/redox dual-sensitive nanoparticles (NPs) based on a poly(ε-caprolactone) (PCL) and polyethylene glycol (PEG) triblock copolymer were developed and investigated aiming at improving the drug release property of PCL in cancer chemotherapy. A redox-sensitive disulfide bond and pH-sensitive benzoic-imine linkers were introduced to the backbone of the amphiphilic block copolymer termed SCHE, which could self-assemble into stable spherical NPs in aqueous solutions with an average size of about 100 nm. Doxorubicin (DOX) as a hydrophobic anticancer drug was loaded into the NPs by a dialysis method. The in vitro drug release results showed that the accumulative release amount of DOX at pH 5.0 with 10 mM glutathione (GSH) was accelerated apparently by more than twice compared to that at pH 7.4 without GSH. After a pre-treatment with GSH, the intracellular fluorescence intensity of Hela cells was enhanced compared to those without the pretreatment, which indicated faster DOX release in cells with higher GSH concentration. In an MTT assay, no obvious toxicity of blank NPs was found. In conclusion, SCHE NPs could serve as a novel colloidal drug delivery system in cancer chemotherapy and the introduced unstable linkers could enhance the drug release rate at tumor sites.

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JOURNAL OF APPLIED POLYMER SCIENCE · 2014 ·Vol. 131 ·期 17 · IF 1.64

Preparation and application in drug controlled delivery of pH-sensitive P(CE-co-DMAEMA-co-MEG) hydrogel

Fang Ping Wang,Jun Ying Zhang,Hu Po Mu,Wan Xia Li,Ting Yuan,Xin Zhen Du

A pH-sensitive hydrogel [P(CE- co -DMAEMA- co -MEG)] was synthesized by the free-radical crosslinking polymerization of N,N -dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG-Mac) and methoxyl poly(ethylene glycol)-poly(caprolactone)-methacryloyl methchloride (PCE-Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled-release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non-Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40737.

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DESALINATION · 2014 · IF 3.96

Toward robust pH-responsive and anti-fouling composite membranes via one-pot in-situ cross-linked copolymerization

Zhiyuan Han,Chong Cheng,Lisha Zhang,Chongdan Luo,Chuanxiong Nie,Jie Deng,Tao Xiang,Changsheng Zhao

This study reports a novel and systematic strategy on the preparation and characterization of pH-responsive and anti-fouling composite membranes via one-pot in-situ cross-linked copolymerization . Typical commercial polyethersulfone (PES) is used as membrane matrix; poly (methyl methacrylate- co -acrylic acid) (P(MMA-AA)) and poly(methyl methylacrylate- co -4vinyl pyridine) (P(MMA-4VPy)) are applied as model pH-responsive copolymers . The casting solutions are directly synthesized by one-pot in-situ cross-linked copolymerization of MMA, AA/4VPy and cross-linker in PES solutions; then, composite membranes are obtained by a liquid–liquid phase inversion method. ATR-FTIR, water contact angle, membrane morphology, pH sensitivity and reversibility , protein anti-fouling property, and Cu 2   + adsorption capacity for the composite membranes are systematically investigated. The cross-section SEM data indicated that the composite membranes owned typical finger-like structure; while the surface SEM images indicated that the in-situ copolymerized system exhibited excellent miscibility between PES and copolymers. The pH-responsive tests proved that the PES/P(MMA-AA) and PES/P(MMA-4VPy) membranes owned remarkable and reversible pH-responsive performance. Protein ultrafiltration experiments showed that the composite membranes exhibited excellent anti-fouling property. Furthermore, the prepared composite membranes exhibited good Cu 2   + adsorption capacity. The results demonstrated that the proposed in-situ cross-linked copolymerization provided a facile and practical approach to fabricate pH-responsive and anti-fouling membranes for various applications.

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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2015 · IF 3.65

Green fabricated reduced graphene oxide: evaluation of its application as nano-carrier for pH-sensitive drug delivery

Naxin Ma,Baohua Zhang,Jing Liu,Pei Zhang,Zhonghao Li,Yuxia Luan

A green and mild approach for the preparation of reduced graphene oxide (rGO) was proposed by using riboflavin-5′-phosphate sodium salt dihydrate as a reducing reagent and stabilizer without any other reagent. The fabricated nano-rGO was systematically evaluated for its application as nano-carrier for pH-sensitive drug delivery. The hemolytic toxicity test indicated the as-prepared nano-rGO had negligible hemolytic activity, which demonstrating its safety in drug delivery system. Doxorubicin hydrochloride (DOX) as a model drug was successfully attached onto the surface of nano-rGO via strong π–π stacking interaction. Compared with common carriers, the obtained DOX-loaded nano-rGO nanohybrid exhibited characteristics of high drug loading content, good stability, pH-sensitive and sustainable release of drugs. Cytotoxicity assay results suggested such nanohybrid exhibited effective cytotoxicity to MCF-7 and A549 cells by nonspecific endocytosis mechanism. Therefore, the present green fabricated rGO could be a good candidate as an ideal nano-carrier for drug delivery and controlled release.

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EUROPEAN POLYMER JOURNAL · 2015 · IF 3.005

Core-crosslinked polymeric micelles with high doxorubicin loading capacity and intracellular pH- and redox-triggered payload release

Yan Zhang,Chenhong Wang,Yunxiao Huang,Husheng Yan,Keliang Liu

Polymeric micelles containing a poly(ethylene glycol) shell and a disulfide-crosslinked core with a hydrophobic moiety and carboxylic acid groups were prepared. The loading of doxorubicin into the core was achieved with a combination of ionic bonding and hydrophobic effects. The cooperativity of these effects enabled doxorubicin to bind tightly to the core, thereby endowing the system with a high loading capacity and a low rate of premature release in the bloodstream. Disulfide crosslinkages prevented the dissociation of the micelles into unimers upon extensive dilution. Under intracellular-like conditions (e.g., pH 5 with the presence of glutathione), the payload was released at a high rate from the micelles. The release was attributed to cleavage of the disulfide crosslinkages by glutathione and disruption of the ionic bonds at a lower pH due to protonation of the carboxylate anions in the core. Intracellular doxorubicin release was found to positively correlate with intracellular glutathione levels.

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JOURNAL OF APPLIED POLYMER SCIENCE · 2015 ·Vol. 132 ·期 29 · IF 1.768

Preparation and aqueous solution behavior of a ph-responsive branched copolymer based on 2-(diethylamino)ethyl methacrylate

Lei Wang,Wen Huang,Shijie Wang,Yuezhi Cui,Pengfei Yang,Xiaodeng Yang,Jonathan V. M. Weaver

pH-Responsive amphiphilic branched copolymers were prepared from poly(ethylene glycol) methyl ether methacrylate (PEGMA), 2-(diethylamino)ethyl methacrylate (DEAEMA), 2-( tert -butylamino)ethyl methacrylate ( t BAEMA), and ethylene glycol dimethacrylate (EGDMA) utilizing a thiol-modified free radical polymerization. The molecular structures of copolymers were confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and triple-detection gel permeation chromatography (tri-GPC). The aqueous solution behaviors of the obtained copolymers were investigated by dynamic light scattering (DLS). The DLS data showed that about 16 nm polymer particles comprising of hydrophobic poly( tert -butylamino)ethyl methacrylate (P t BAEMA) and poly(diethylaminoethyl methacrylate (PDEAEMA) core, hydrophilic PEGMA corona were formed above pH 8. With the decrease of pH from 8 to 6, a dramatic increase in the hydrodynamic radius of polymer particles from 16 nm to 130 nm was observed resulting from the protonation of the PDEAEMA segment. Moreover, in vitro drug release behaviors of the resulting polymer assemblies at different pH values were also investigated to evaluate their potential as sustained release drug carriers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42183.

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Polymer Chemistry · 2015 ·Vol. 6 ·期 11 ·2098-2107 · IF 5.52

pH-responsive dendritic polyrotaxane drug-polymer conjugates forming nanoparticles as efficient drug delivery system for cancer therapy

Yang Kang,Xiao-Mei Zhang,Sheng Zhang,Li-Sheng Ding,Bang-Jing Li

Self-assembly of stimuli-responsive polymeric nanoparticles have attracted great attention in recent years due to their prospective biological applications. This paper developed a novel pH-sensitive amphiphilic dendritic polyrotaxane drug-polymer conjugate by covalently linking doxorubicin (DOX) and dendritic polyrotaxane via a pH-responsible hydrazone bond with 1.84 wt% (weight percent) of DOX. The drug-polymer conjugate was amphiphilic and could be self-assembled to micelles (PR-g-DOX micelles) in an aqueous solution. The globular morphology and compact micelles with a diameter of around 110 nm were observed by SEM and TEM. Moreover, the micelles showed a significantly faster DOX release at mildly acidic pH of 6.0 and 5.0 and almost no burst release at the physiological pH of 7.4. Notably, it was confirmed that this micelle could efficiently deliver DOX to the nuclei of the tumor cells, which led to a much greater cytotoxic effects in the A549 cancer cells than the parent DOX. In vivo results revealed better drug tolerability of PR-g-DOX micelles and a higher in vivo efficacy without any increase in the toxicity of the PR-g-DOX micelles. Furthermore, the maximum tolerated dose (MTD) results showed that PR-g-DOX micelles showed an excellent safety profile with a two-fold higher MTD (10 mg kg−1 DOX) than that of free DOX (5 mg kg−1 DOX). We are convinced that the PR-g-DOX micelle has tremendous potentials for targeted cancer therapy.

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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2014 · IF 3.552

Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug

Rongrong Li,Fuli Feng,Yinsong Wang,Xiaoying Yang,Xinlin Yang,Victor C. Yang

The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive poly(methacrylic acid- co - N , N -bis(acryloyl)cystamine/poly( N -isopropylacrylamide- co -glycidyl methacrylate- co - N , N -bis(acryloyl)cystamine) microspheres were prepared by a two-stage distillation–precipitation polymerization with subsequent surface modification with FA . The microspheres were characterized by transmission electron microscopy, dynamical light scattering, Fourier-transform infrared spectra, UV–vis spectra and elemental analysis. The degradation of the functional microspheres could be triggered by a reductive reagent, such as glutathione, due to presence of BAC crosslinker. The drug-loaded microspheres exhibited a pH/temperature/redox multi-stimuli responsive drug release character for doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently loaded into the microspheres with a high loading capacity of 208.0% and an encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that the FA-conjugated microspheres could deliver Dox into MCF-7 cells more efficiently than the microspheres without functionalization of FA. Furthermore, WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells even at a high concentration of 2000   μg   mL −1 . The resultant microsphere may be a promising vector for delivery of anti-cancer drugs as it exhibits a low cytotoxicity and degradability, precise molecular targeting property and multi-stimuli responsively controlled drug release.

CAS / MDL: 106-91-2
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