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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2015 · IF 3.368

Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy

Danfeng Chang,Yongfeng Gao,Lijun Wang,Gan Liu,Yuhan Chen,Teng Wang,Wei Tao,Lin Mei,Laiqiang Huang,Xiaowei Zeng

A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs–DES–PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs–DES–PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs–DES and MSNs–DES–PDA were totally different, and the drug release of MSNs–DES–PDA accelerated with increasing acidity. MSNs–DES–PDA can be internalized into cells. In vitro experiments demonstrated that MSNs–DES–PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy.

CAS / MDL: 12125-01-8
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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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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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ANALYTICA CHIMICA ACTA · 2015 · IF 4.513

pH-controlled quaternary ammonium herbicides capture/release by carboxymethyl-β-cyclodextrin functionalized magnetic adsorbents: Mechanisms and application

Chang Liu,Peng Wang,Zhigang Shen,Xueke Liu,Zhiqiang Zhou,Donghui Liu

In our work, the pH-controlled magnetic solid phase extraction for the determination of paraquat and diquat was introduced firstly. Furthermore, to clarify the mechanism of carboxymethyl-β-cyclodextrin functionalized magnetic adsorbents, we studied the pH-responsive supramolecular interaction between carboxymethyl-β-cyclodextrin (CM-β-CD) and paraquat/diquat by ultraviolet–visible (UV–vis) spectroscopy and nuclear magnetic resonance (NMR) experiment, and the energy-minimized structures were also obtained. Then, the functional group CM-β-CD was modified on the surface of magnetic materials to synthesize the adsorbent. The Fourier transform infrared spectrum (FT-IR) results proved the successful modification of CM-β-CD. Thus, this absorbent was applied for the determination of paraquat and diquat in water. Under the optimal condition, limits of detection (LODs) of paraquat and diquat were 0.8 μg L −1 and 0.9 μg L −1 , relative standard deviations (RSD) and recoveries varied 0.7–4.6% and 86.5–106.6%, respectively. Good recoveries (70.2–100.0%) and low RSD (1.7–9.6%) were achieved in analyzing spiked water samples. Furthermore, with the capillary electrophoresis (CE) as the analyser, the whole analytical process did not need the attendance of organic solvents .

CAS / MDL: 420-04-2 1317-61-9
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APPLIED SURFACE SCIENCE · 2015 · IF 2.711

Targeted delivery and pH-responsive release of stereoisomeric anti-cancer drugs using β-cyclodextrin assemblied Fe3O4 nanoparticles

Congli Wang,Lizhen Huang,Shengmei Song,Bassam Saif,Yehong Zhou,Chuan Dong,Shaomin Shuang

The β-cyclodextrin assemblied magnetic Fe 3 O 4 nanoparticles (β-CD-MNPs) were successfully fabricated via a layer-by-layer method. Possessing an average size 14   nm, good stability and super-paramagnetic response (Ms 64   emu/g), the resultant nanocomposites could be served as a versatile biocompatible platform for selective loading, targeted delivery and pH-responsive release of stereoisomeric doxorubicin (DOX) and epirubicin (EPI). 1 H-nuclear magnetic resonance ( 1 H NMR) and the computer simulation further give the evidence that partial anthracene ring of drug molecule is included by β-CD. In addition, non-toxic β-CD-MNPs have excellent biocompatibility on MCF-7 cells, and cellular uptake indicate that different amounts of DOX or EPI can be transported to targeting site and released from the internalized carriers. The results demonstrate that as-prepared β-CD-MNPs could be a very promising vehicle for DOX and EPI.

CAS / MDL: 919-30-2 872-50-4
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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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TALANTA · 2015 · IF 3.545

A tunable pH-sensing system based on Ag nanoclusters capped by hyperbranched polyethyleneimine with different molecular weights

Fei Qu,Xuan Zou,Rongmei Kong,Jinmao You

In this assay, a tunable pH sensing system was developed based on Ag nanoclusters (Ag NCs) capped by hyperbranched polyethyleneimine (PEI) with different molecular weights (abbreviated as Ag NC-PEIs). For instance, when the molecular weight of PEI was 600 or 1800, the fluorescence intensities of Ag NCs exhibited a linear fashion over the pH range 4.10–7.96; when the molecular weight of PEI was 25,000, the pH linear range was from 4.78 to 7.96; when the molecular weight of PEI was 70,000, the pH linear range was 6.09–8.95. According to the molecular weight of PEI 600/1800, 25,000, and 70,000, the color change point was pH 4.10–4.78, 5.33–6.09, and 6.09–6.80, respectively. Therefore, Ag NC-PEI 600 and 1800 were proper to acid conditions; Ag NC-PEI 25,000 was sensitive to weak acid media; while Ag NC-PEI 70,000 was adapted to neutral solution. The tunable and selective color change points brought an excellent feature of Ag NC-PEIs as visual pH indicators, which was flexible and applicable to a variety of environments. Besides, the ratios of absorbance at 415   nm and 268   nm of Ag NCs also showed linear relationships with pH variations. Therefore, there were three ways of this system for sensing pH values, including fluorescence assay, ultraviolet–visible measurement, and visual detection, suggesting that this tunable pH-sensing platform was more feasible, reliable, and accurate.

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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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NANOTECHNOLOGY · 2013 ·Vol. 24 ·期 36 ·365101 · IF 3.842

A low cytotoxic and ratiometric fluorescent nanosensor based on carbon-dots for intracellular pH sensing and mapping

Fangkai Du,Yunhao Ming,Fang Zeng,Changmin Yu,Shuizhu Wu

Intracellular pH plays a critical role in the function of cells, and its regulation is essential for most cellular processes. In this study, we demonstrate a fluorescence resonance energy transfer (FRET)-based ratiometric pH nanosensor with carbon-dot (CD) as the carrier. The sensor was prepared by covalently linking a pH-sensitive fluorescent dye (fluorescein isothiocyanate, FITC) onto carbon-dot. As the FRET donor, the carbon-dot exhibits bright fluorescence emission as well as λex-dependent photoluminescence emission, and a suitable excitation wavelength for the donor (CD) can be chosen to match the energy acceptor (fluorescein moiety). The fluorescein moieties on a CD undergo structural and spectral conversion as the pH changes, affording the nanoplatform a FRET-based pH sensor. The CD-based system exhibits a significant change in fluorescence intensity ratio between pH 4 and 8 with a pKa value of 5.69. It also displays excellent water dispersibility, good spectral reversibility, satisfactory cell permeability and low cytotoxicity. Following the living cell uptake, this nanoplatform with dual-chromatic emissions can facilitate real-time visualization of the pH evolution involved in the endocytic pathway of the nanosensor. This reversible and low cytotoxic fluorescent nanoplatform may be highly valuable in a variety of biological studies, such as endocytic trafficking, endosome/lysosome maturation, and pH regulation in subcellular organelles.

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COLLOID AND POLYMER SCIENCE · 2015 ·Vol. 293 ·期 10 ·2979-2984 · IF 1.865

Design of new lanthanide pH switches based on a cross-linked poly(vinyl alcohol)/tetraethoxysilane hybrid matrix

Su Rong,Wang Qianming

The design and synthesis of cross-linked siloxane and polymeric matrices incorporated with terbium or europium complexes have been studied. The preparation of hybrid hosts demonstrated that poly(vinyl alcohol) in the presence of tetraethoxysilane with various concentrations gave different mechanical stabilities and water solubilities. The as-derived films exhibited excellent photophysical properties of lanthanides with large Stokes shifts, narrow emissions, and high color purity. It has been found that the luminescent materials were dramatically quenched over the assayed pH ranges (pH 7 to 1 and pH 7 to 14). These optical probes could be recycled for ten times by changing the aqueous media. The novel inorganic-organic responsive films that can be switched on or off based on pH values will find potential application in biological analysis.

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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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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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