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MOLECULAR PHARMACEUTICS · 2014 · IF 4.787

pH-Sensitive Fluorescent Hepatocyte-Targeting Multilayer Polyelectrolyte Hollow Microspheres as a Smart Drug Delivery System

Xubo Zhao,Peng Liu

Novel multilayer polyelectrolyte hollow microspheres with pH-sensitive fluorescence and hepatocyte-targeting functions were successfully fabricated via a layer-by-layer (LbL) assembly of fluorescein isothiocyanate (FITC)-modified chitosan (CSFITC) and sodium hyaluronate (HA) (as the polycation and polyanion, respectively) on polystyrene sulfonate (PSS) templates with galactosylated chitosan (GC) as the outermost layer; after etching the templates by dialysis, the aim was to use the microspheres to target hepatocytes specifically. TEM analysis revealed that they have a hollow structure with a particle size of about 260 nm, and DLS analysis demonstrated that they have pH and ionic strength dual-responsive characteristics. The hollow microspheres showed pH-sensitive fluorescence at a very low concentration by fluorescent emission spectra. MTT assays revealed that doxorubicin (a water-insoluble anticancer drug)-loaded (CSFITC/HA)4/GC hollow microspheres can specifically target hepatocytes and exhibit favorable cytocompatibility. Three typical model drugs were loaded into the (CSFITC/HA)4/GC hollow microspheres, and their drug-release kinetics in simulated body fluid (SBF) were estimated with different mathematical models. The results demonstrated that the drug-loading mechanism is chemosorption and the primary governing force for drug release is diffusion. Thus, the designed hollow microspheres are expected to be used for the diagnosis and therapy of hepatic cancer.

CAS / MDL: 6066-82-6
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JOURNAL OF HAZARDOUS MATERIALS · 2013 · IF 3.925

Enhanced decomposition of dyes by hemin-ACF with significant improvement in pH tolerance and stability

Yuyuan Yao,Yajun Mao,Qunfeng Huang,Lie Wang,Zhengfu Huang,Wangyang Lu,Wenxing Chen

In this study, we evaluated a novel heterogeneous catalytic system (hemin-ACF/H 2 O 2 ) based on activated carbon fiber supported hemin for the rapid removal of dyes. Contrast experiments, effects of pH and temperature, and sustained catalytic stability of hemin-ACF for the catalytic decomposition of azo dye RR195 used as a model pollutant were investigated. Surprisingly, the introduction of ACF significantly enhanced the decomposition of dyes by hemin with an obvious improvement in pH tolerance and stability. Inhibition and probe studies combined with electron paramagnetic resonance (EPR) were conducted to ascertain the role of several radicals ( OH, O 2 − /HO 2 , 1 O 2 and Fe IV O) on dye degradation. ACF are rich in free electrons, and the π-conjugated macrocyclic structure of hemin may present convenient channels for the transfer of free electrons from the ACF, promoting the generation of hydroxyl radicals and high-valence iron species. These results are promising because they offer new insight for the application of hemin as a catalyzer upon treatment of organic pollutants and contribute to identification of the interaction between support material and catalyzer from a new perspective.

CAS / MDL: 16009-13-5
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2013 ·Vol. 405 ·期 18 ·5993-5999 · IF 3.659

A duplex–triplex nucleic acid nanomachine that probes pH changes inside living cells during apoptosis

Li Xue-Mei,Song Jian,Cheng Tao,Fu Pei-Yu

A duplex–triplex switchable DNA nanomachine was fabricated and has been applied for the demonstration of intracellular acidification and apoptosis of Ramos cells, with graphene oxide (GO) not only as transporter but also as fluorescence quencher. The machine constructed with triplex-forming oligonucleotide exhibited duplex–triplex transition at different pH conditions. By virtue of the remarkable difference in affinity of GO with single-stranded DNA and triplex DNA, and the super fluorescence quenching efficiency of GO, the nanomachine functions as a pH sensor based on fluorescence resonance energy transfer. Moreover, taking advantage of the excellent transporter property of GO, the duplex–triplex/GO nanomachine was used to sense pH changes inside Ramos cells during apoptosis. Fluorescence images showed different results between living and apoptotic cells, illustrating the potential of DNA scaffolds responsive to more complex pH triggers in living systems. The caption/legend for the online abstract figure: Schematic illustration of cell apoptosis detection in Ramos cells by using duplex-triplex/GO nanocomplex

CAS / MDL: 2068-78-2
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LANGMUIR · 2015 · IF 4.457

Preparation of Novel Porphyrin Nanomaterials Based on the pH-Responsive Shape Evolution of Porphyrin Microspheres

Wenbo Zhang,Lingbo Xing,Haisheng Wang,Xiujun Liu,Yaqing Feng,Changyou Gao

The shapes and properties of self-assembled materials can be adjusted easily using environmental stimuli. Yet, the stimulus-triggered shape evolution of organic microspheres in aqueous solution has rarely been reported so far. Here, a novel type of poly(allylamine hydrochloride)-g-porphyrin microspheres (PAH-g-Por MPs) was prepared by a Schiff base reaction between 2-formyl-5,10,15,20-tetraphenylporphyrin (Por-CHO) and PAH doped in 3.5-μm CaCO3 microparticles, followed by template removal. The PAH-g-Por MPs had an average diameter of 2.5 μm and could be transformed into one-dimensional nanorods (NRs) and wormlike nanostructures (WSs) after being incubated for different times in pH 1–4 HCl solutions. The rate and degree of hydrolysis had a significant effect on the formation and morphologies of the nanorods. The NRs@pH1, NRs@pH2, and NRs@pH3 were all composed of the released Por-CHO and the unhydrolyzed PAH-g-Por because of the incomplete hydrolysis of the Schiff base. However, the WSs@pH4 were formed by a pure physical shape transformation, because they had the same composition as the PAH-g-Por MPs and the Schiff base bonds were not hydrolyzed. The self-assembled NRs and WSs exhibited good colloidal stability and could emit stable red fluorescence over a relatively long period of time.

CAS / MDL: 109-97-7
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EUROPEAN JOURNAL OF INORGANIC CHEMISTRY · 2015 ·Vol. 2015 ·期 13 ·2277-2284 · IF 2.942

pH-Sensitive Gold Nanorods with a Mesoporous Silica Shell for Drug Release and Photothermal Therapy

Ting Zhang,Zeyang Ding,Huiming Lin,Liru Cui,Chunyu Yang,Xin Li,Hao Niu,Na An,Ruihan Tong,Fengyu Qu

Graphical A pH-sensitive nanocarrier with a gold nanorod (GNRs) core and mesoporous silica shell (GNR@mSiO 2 ) was synthesized. Doxorubicin hydrochloride (DOX) was loaded onto the mesoporous silica with Schiff base bonding, and enhanced drug release was observed under acidic conditions owing to the sensitive Schiff base linker. The synergistic effect of chemotherapy and hyperthermia shown by this nanocarrier can be expected to lead to improved cancer treatment. A pH-sensitive nanocarrier has been developed for the controlled intracellular release of drugs. The nanocarrier, which is approximately 75 nm in size, is composed of a gold nanorod (GNR) core and mesoporous silica shell (GNR@mSiO 2 ) and shows good stability and biocompatibility, and excellent photothermal effects. Doxorubicin hydrochloride (DOX), a typical anticancer drug, was adopted as the model drug, and was connected to the mesoporous silica through Schiff base bonding. The drug-loading nanocarriers (GNR@mSiO 2 -DOX) exhibit enhanced drug release under acidic conditions owing to the sensitive Schiff base linker, whereas at high pH values low levels of premature release can be detected. The sensitive release mechanism was further investigated by monitoring the zeta potential before and after drug release. HeLa cells were used as typical cancer cells, and detailed cell experiments were carried out to confirm the good biocompatibility, rapid uptake, and acid-enhanced drug delivery of GNR@mSiO 2 -DOX. Moreover, the synergistic effect of chemotherapy and hyperthermia (photothermal effect from GNRs) of the nanocarrier can be expected to lead to improved therapy effects on cancer treatment.

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COLLOID AND POLYMER SCIENCE · 2015 ·Vol. 293 ·期 6 ·1759-1766 · IF 1.865

Study of pH-responsive surface active ionic liquids: the formation of spherical and wormlike micelles

Yan Zhihu,Dai Caili,Zhao Mingwei,Li Yuyang,Du Mingyong,Peng Dongxu

A noncovalent bonding method is utilized for forming pH-responsive surface active ionic liquids in mixed N -hexadecyl- N -methylpyrrolidinium bromide-based cationic surfactant (C 16 MPBr) and potassium phthalic acid (PPA). Rheology, cryogenic-transmission electron microscopy, and dynamic light scattering results revealed that the microstructure transition between spherical micelles and wormlike micelles was the fundamental cause of the pH-sensitive rheological properties. In addition, combined with nuclear magnetic resonance and UV–vis analysis, we found that the structure transition of micelles was attributed to different binding abilities of hydrotropes to C 16 MPBr as pH varies. It is confirmed that the binding ability of PPA to C 16 MPBr is strongest. This noncovalent bonding method is not only versatile but also economical for fabricating pH-responsive surface active ionic liquids.

CAS / MDL: 452072-22-9
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2016 · IF 1.733

Release profile of insulin from pH-sensitive hydrogel and its hypoglycemic effect by oral administration

Yongli Shi,Xiao Wang,Xiuzhen Deng,Ruiqiong Tian,Yuehong Zhang,Qing Shang,Nan Chen

The purpose of this study was to investigate the release profile and in vivo hypoglycemic effect of insulin (INS)-loaded pH-sensitive hydrogel (INS-TPM950) administrated by oral route. TPM950 was fabricated via a free polymerization method and its inner morphology was observed with a scanning electron microscope (SEM). INS was encapsulated into TPM950 by an adsorption method, and the in vitro release profiles of INS from INS-TPM950 were revealed in pH 1.2 and 6.8. To investigate the hypoglycemic effect of INS-TPM950, Male Wistar rats were used in modeling of diabetes mellitus by multiple intraperitoneal injection of alloxan. The in vivo hypoglycemic effect of oral INS-TPM950 was studied, and the optimal dosage was also determined. SEM photograph showed that abundant 3D meshes were distributed in the inner of TPM950 hydrogel. INS release profile suggested that only 18.2 ± 11.3% INS was released in pH 1.2, but over 88.8 ± 4.9% was delivered into phosphate buffer solution in pH 6.8. After injection to the diabetic rats, the released INS solution from INS-TPM950 exhibited an obvious hypoglycemic effect. Oral administration of 50.0 I.U./kg of INS-TPM950 showed a slow but effective hypoglycemic effect, and the lowest blood glucose level was reached to 47.5 ± 5.5% of the original level. Therefore, this formulation had a potential application in diabetes treatment via oral ingestion.

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CARBOHYDRATE POLYMERS · 2015 · IF 4.074

Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug

Wuxia Zhang,Dongqi Dong,Peng Li,Dongdong Wang,Haibo Mu,Hong Niu,Jinyou Duan

Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72   h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72   h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2014 · IF 4.287

pH and hydrogen peroxide dual responsive supramolecular prodrug system for controlled release of bioactive molecules

Yin Wang,Haibo Wang,Yangjun Chen,Xiangsheng Liu,Qiao Jin,Jian Ji

Nowadays, cancer is one of the most fatal threatens to human health. By utilizing the differences of cell environment between cancer cells and their normal counterparts as assembly-disassembly triggers, various smart drug nanocarriers have been designed to fight the cancer. Nevertheless, most of them are still not robust enough. One important reason is that they merely focus on a single stimulus. Thus, in order to achieve a better therapeutic effect, constructing multi responsive polymers is of great significance. However, most of multi responsive polymers used, up until now, are mainly based on block polymers synthesized via traditional polymerization methods, which are relatively time-consuming and laborious. Here in this article, a facile strategy preparing smart polymers with dual responsiveness (endosomal pH and over produced H 2 O 2 ) was proposed and realized by orthogonal assembly of β-CD-hydrazone-DOX and PEG-Fc. The obtained polymers were found to be able to spontaneously assemble into micelles in water, indicating their potential applications as drug nanocarriers. In vitro study revealed that the release of the encapsulated DOX was significantly enhanced by both H 2 O 2 and low pH at 5.0. Furthermore, fluorescence microscopy and flow cytometry analysis showed that the assembled supramolecular prodrug micelles could be internalized into cancer cells. These properties suggested their promising application in cancer therapy.

CAS / MDL: 1271-42-7
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ANALYTICA CHIMICA ACTA · 2014 · IF 4.517

Novel lanthanide pH fluorescent probes based on multiple emissions and its visible-light-sensitized feature

Jintai Lin,Yuhui Zheng,Qianming Wang,Zhi Zeng,Cheng Cheng Zhang

A new type of Eu(III) ofloxacin complex as the fluorescent pH indicator has been presented. Compared to pure ligand, the complex offers more distinguished color changes (green–red–blue) derived from both lanthanide line emissions and the secondary ionization steps of ofloxacin. During the concentration dependence experiments, the photoluminescence studies on the complex showed that the excitation of this pH probe can occur at a very long wavelength which extends to visible range (Ex   =   427   nm). Furthermore, the functional complex was successfully incorporated into soft networks and two novel luminescent hydrogels (rod and film) were fabricated. The soft materials also exhibited specific responses towards the pH variation. Finally, the onion cell-stain experiments were carried out to further confirm the validity of pH dependence and the results support the idea that the material will be suitable for monitoring biological samples in the future.

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RSC Advances · 2017 ·Vol. 7 ·期 36 ·22079-22085 · IF 3.108

pH responsive vesicles with tunable size formed by single-tailed surfactants with a dendritic headgroup

Hongtao Xie,Wensheng Lu,Jide Wang,Wei Wang

The structure–activity relationship of surfactants is a topic that has been pursued for a long time in colloid science. We report a study on the self-assembling of a new type of surfactant with a dendritic headgroup in dilute aqueous solutions. Three surfactants, N-alkyldipropionic acids (ADPA) with different chain lengths (n = 14, 16, and 18), were synthesized. As a result of the carboxylic acids and one tertiary amine in the headgroup, the protonation state of the surfactants changes with pH. The morphology of the surfactant aggregates in aqueous solutions was studied at various pH values by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Vesicles were formed spontaneously at pH > 5. Potentiometric titration, turbidity and surface tension were used to determine the effect of protonation state on aggregation behavior. The results show that the vesicle size depends directly on the pH of the solution. The size distribution of vesicles was analyzed by the model of spontaneous curvature. The thermodynamic stability of the vesicles can be attributed to long-range repulsive interactions caused by the low bending modulus of the bilayers.

CAS / MDL: 1310-73-2
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