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COLLOIDS AND SURFACES B-BIOINTERFACES · 2015 · IF 4.152

Hyaluronic acid and polyethylenimine self-assembled polyion complexes as pH-sensitive drug carrier for cancer therapy

Jing-Xiao Chen,Min Wang,Hui-Hui Tian,Jing-Hua Chen

In this study, a series of polyion complexes (PICs) were prepared via electrostatic interaction between hyaluronic acid–histidine conjugate (HH) and polyethylenimine–histidine conjugate (PH). These PICs with the average size ranging from 410.5   nm to 98.5   nm at different weight ratios of HH/PH were able to encapsulate doxorubicin (DOX) as the model antitumor drug. The PICs at the weight ratio of 4:1 had negative surface charge and were of good dispersity and stability in the solution containing serum. In vitro drug release assay demonstrated that the DOX release rate were higher at acidic pH showing a controllable property. These HA coated PICs could targetedly deliver DOX to B16F10 tumor cells, showing improved antitumor activity.

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Advanced Healthcare Materials · 2014 ·Vol. 4 ·期 3 ·413-419 · IF 4.88

Probing the Endocytic Pathways of the Filamentous Bacteriophage in Live Cells Using Ratiometric pH Fluorescent Indicator

Ye Tian,Man Wu,Xiangxiang Liu,Zhi Liu,Quan Zhou,Zhongwei Niu,Yong Huang

Viral nanoparticles have attracted extensive research interests in diverse applications of diagnosis and therapy. In particular, filamentous M13 bacteriophages have shown great potential in biomedical applications. However, its pathways entering into cells still remain unclear, and this greatly hinders its further use as a drug or gene carrier. Here, a ratiometric M13 pH probe is designed by conjugating two fluorescent dyes onto the surface of M13. Since the intensity ratio is not influenced by probe concentration, ion strength, temperature, photobleaching, and optical path length, this ratiometric probe can be used to investigate the intracellular pH map of M13. More importantly, the internalization mechanism of M13 can be elucidated. It is found that this filamentous phage shows great cell-type dependence in interaction with cells and internalization mechanism. The phage tends to be bounded on the cell membrane of only epithelial cells, not endothelial cells. Furthermore, the M13 phage enters into cells through endocytosis with specific mechanism: clathrin-mediated endocytosis and macropinocytosis for HeLa; vesicular transport, clathrin-mediated endocytosis, and macropinocytosis for MCF-7; caveolae-mediated endocytosis for human dermal microvascular endothelial cell (HDMEC). This work provides key notes for cancer diagnosis and therapy based on filamentous bacteriophage, especially for design of pH-sensitive drug delivery systems.

CAS / MDL: 128-53-0 127-09-3
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JOURNAL OF HAZARDOUS MATERIALS · 2015 · IF 4.529

Toxicity and bioaccumulation of copper in Limnodrilus hoffmeisteri under different pH values: Impacts of perfluorooctane sulfonate

Lingjun Meng,Shaogui Yang,Mingbao Feng,Ruijuan Qu,Yong Li,Jiaoqin Liu,Zunyao Wang,Cheng Sun

Aquatic oligochaete Limnodrilus hoffmeisteri ( L. hoffmeisteri ) has been commonly used as a lethal and/or sub-lethal toxicological model organism in ecological risk assessments in contaminated water environments. In this study, experiments were conducted to investigate the potential toxic effects of copper (Cu(II)) with or without perfluorooctane sulfonate (PFOS) under different pH values (6.0, 7.0 and 8.0) on LC 50 , bioaccumulation, and oxidative stress biomarkers in L. hoffmeisteri after 3 and 7 days. The LC 50 values of Cu(II) decreased with the increasing pH and the addition of PFOS. After each exposure, increasing bioaccumulation of Cu(II) in L. hoffmeisteri was observed in the combined exposure treatments, whereas the bioaccumulation of PFOS decreased. Moreover, the activity of superoxide dismutase, the level of glutathione, and the content of malondialdehyde were significantly altered after these exposures, possibly indicating that the bioaccumulation of Cu(II) and PFOS caused adverse effects on antioxidant defenses of L. hoffmeisteri . The integrated biomarker response index, indicates that the combined effect was proposed as synergism, which is coincided with the results of toxic unit. Moreover, this work showed that aquatic environment may become more livable when water conditions changed from acidic to near-neutral or alkaline.

CAS / MDL: 1132-61-2
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RSC Advances · 2015 ·Vol. 5 ·期 26 ·20595-20602 · IF 3.84

A novel AgNPs-based colorimetric sensor for rapid detection of Cu2+ or Mn2+ via pH control

Genhua Wu,Chen Dong,Yonglong Li,Zhuqing Wang,Yuexia Gao,Zheyu Shen,Aiguo Wu

In this study, we propose a new silver nanoparticles (AgNPs)-based colorimetric sensor for rapid detection of Cu2+ or Mn2+ at pH 1.9 or 12.0, respectively. At pH 1.9, the AgNPs stabilized with sodium pyrophosphate (Na4P2O7) and hydroxypropylmethylcellulose (HPMC) gradually become smaller in the presence of Cu2+ resulting in a color change of the solution from yellow to colorless. At pH 12.0, however, the AgNPs aggregate immediately in the presence of Mn2+, which induces a color change of the solution from yellow to brown. The incubation time between the detection system and metal ion (Cu2+ or Mn2+) is fixed at 10 min. This mechanism is confirmed using UV-vis spectroscopy, Transmission electron microscopy (TEM), Dynamic light scattering (DLS) and Fourier-Transform Infrared Spectrometry (FT-IR). At the optimized experimental conditions, the selectivity of our AgNPs-based detection system is excellent for Cu2+ or Mn2+ compared with other metal ions. The limit of detections (LODs) of Cu2+ and Mn2+ by the naked eye are respectively 0.05 and 0.5 μM, and those by UV-vis spectroscopy are respectively 2.0 and 20 nM. The above LODs are all lower than the corresponding national drinking water standards (16 μM of Cu2+ and 1.8 μM of Mn2+). The applicability of our AgNPs-based colorimetric sensor is also validated by detection of Cu2+ and Mn2+ in tap water and lake water. Therefore, these results reinforce that our AgNPs-based colorimetric sensor is applicable to rapid colorimetric detection of Cu2+ and Mn2+ in complicated real water samples with excellent selectivity and high sensitivity.

CAS / MDL: 9004-65-3
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Small · 2015 ·Vol. 11 ·期 21 ·2543-2554 · IF 8.368

Dual-pH Sensitive Charge-Reversal Polypeptide Micelles for Tumor-Triggered Targeting Uptake and Nuclear Drug Delivery

Shi-Song Han,Ze-Yong Li,Jing-Yi Zhu,Kai Han,Zheng-Yang Zeng,Wei Hong,Wen-Xin Li,Hui-Zhen Jia,Yun Liu,Ren-Xi Zhuo,Xian-Zheng Zhang

A novel dual-pH sensitive charge-reversal strategy is designed to deliver antitumor drugs targeting to tumor cells and to further promote the nuclei internalization by a stepwise response to the mildly acidic extracellular pH (≈6.5) of a tumor and endo/lysosome pH (≈5.0). Poly( l -lysine)- block –poly( l -leucine) diblock copolymer is synthesized and the lysine amino residues are amidated by 2,3-dimethylmaleic anhydride to form β-carboxylic amide, making the polypeptides self-assemble into negatively charged micelles. The amide can be hydrolyzed when exposed to the mildly acidic tumor extracellular environment, which makes the micelles switch to positively charged and they are then readily internalized by tumor cells. A nuclear targeting Tat peptide is further conjugated to the polypeptide via a click reaction. The Tat is amidated by succinyl chloride to mask its positive charge and cell-penetrating function and thus to inhibit nonspecific cellular uptake. After the nanoparticles are internalized into the more acidic intracellular endo/lysosomes, the Tat succinyl amide is hydrolyzed to reactivate the Tat nuclear targeting function, promoting nanoparticle delivery into cell nuclei. This polypeptide nanocarrier facilitates tumor targeting and nuclear delivery simultaneously by simply modifying the lysine amino residues of polylysine and Tat into two different pH-sensitive β-carboxylic amides.

CAS / MDL: 188860-26-6 543-20-4
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ACS Applied Materials & Interfaces · 2014 · IF 5.9

Hyaluronic Acid-Decorated Graphene Oxide Nanohybrids as Nanocarriers for Targeted and pH-Responsive Anticancer Drug Delivery

Erqun Song,Weiye Han,Cheng Li,Dan Cheng,Lingrui Li,Lichao Liu,Guizhi Zhu,Yang Song,Weihong Tan

A novel nanohybrid of hyaluronic acid (HA)-decorated graphene oxide (GO) was fabricated as a targeted and pH-responsive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for tumor therapy. For the preparation, DOX was first loaded onto GO nanocarriers via π–π stacking and hydrogen-bonding interactions, and then it was decorated with HA to produce HA–GO–DOX nanohybrids via H-bonding interactions. In this strategy, HA served as both a targeting moiety and a hydrophilic group, making the as-prepared nanohybrids targeting, stable, and disperse. A high loading efficiency (42.9%) of DOX on the nanohybrids was also obtained. Cumulative DOX release from HA–GO–DOX was faster in pH 5.3 phosphate-buffered saline solution than that in pH 7.4, providing the basis for pH-response DOX release in the slightly acidic environment of tumor cells, while the much-slower DOX release from HA–GO–DOX than DOX showed the sustained drug-release capability of the nanohybrids. Fluorescent images of cellular uptake and cell viability analysis studies illustrated that these HA–GO–DOX nanohybrids significantly enhanced DOX accumulation in HA-targeted HepG2 cancer cells compared to HA-nontargeted RBMEC cells and subsequently induced selective cytotoxicity to HepG2 cells. In vivo antitumor efficiency of HA–GO–DOX nanohybrids showed obviously enhanced tumor inhibition rate for H22 hepatic cancer cell-bearing mice compared with free DOX and the GO–DOX formulation. These studies suggest that the HA–GO–DOX nanohybrids have potential clinical applications for anticancer drug delivery.

CAS / MDL: 1071-93-8 25952-53-8
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MACROMOLECULAR BIOSCIENCE · 2013 ·Vol. 14 ·期 3 ·369-379 · IF 3.742

Enhancement of All-Trans Retinoic Acid-Induced Differentiation by pH-Sensitive Nanoparticles for Solid Tumor Cells

Yongjian Wang,Huizhen Wang,Xueming Lv,Congcong Liu,Linshuang Qi,Xindi Song,Ao Yu

Cancer differentiation therapy is an attractive concept and has been clinically used to treat leukemia. However, it is limited to date for solid tumors. In this study, the pH-sensitive nanoparticles based on poly(amidoamine) (PAMAM) dendrimers are synthesized by coupling 3,4,5,6-tetrahydrophthalic anhydride with the first generation PAMAM. The modified dendrimers can self-assemble in aqueous solution to form nanoparticles with a diameter of 125–435 nm. The nanoparticles are relatively stable at physiological pH (pH 7.4) but dissociated in acidic environments (pH 5.0 or 6.0). The present studies show that the proliferation inhibition and albumin secretion of hepatoma carcinoma cells are enhanced with all- trans retinoic acid (ATRA) encapsulated in the nanoparticles. The enhancement of induced differentiation is due to the high internalization of ATRA in the cells by the nanoparticles. These experimental results demonstrate that pH-sensitive nanoparticles may be efficient for improving the differentiation therapy for solid tumor.

CAS / MDL: 85-43-8
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Polymer Chemistry · 2015 ·Vol. 6 ·期 18 ·3529-3536 · IF 5.52

Polyelectrolyte/mesoporous silica hybrid materials for the high performance multiple-detection of pH value and temperature

Feng Chen,Xiaoping Jiang,Tairong Kuang,Lingqian Chang,Dajiong Fu,Jintao Yang,Ping Fan,Mingqiang Zhong

Mesoporous silica nanoparticles have been widely adopted in energy, biology and medicine due to their well-ordered and stable structures. Nevertheless, few attempts have been made to study these materials as a sensing tool. Herein, we report a “smart” sensor for the dual-detection of the pH value and temperature, which was implemented with environmentally responsive polyelectrolyte/mesoporous silica electrodes. Using SBA-15 silica as the framework, we functionalized the internal mesopores with DMAMEA monomer via surface-initiated RAFT polymerization (“grafting-from” method). By controlling the degree of polymerization, the pore size and the specific surface area can be precisely controlled. When the degree of polymerization was optimized to 75, the hybrid material showed significant sensitivity in response to the pH value in the range of 4–10 and optimally responded to the temperature at 39 °C, setting a pH value of 10. The ionic conductivities of the template Fe(CN)64−/3− and Ru(NH3)62+/3+ ions were switchable in different conditions. These results suggest that the polyelectrolyte/mesoporous silica hybrid materials could have potential for application in dual-functional sensors in environmental detection.

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Nanoscale · 2015 ·Vol. 8 ·期 1 ·104-116 · IF 7.394

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

Wenxiu Hou,Xin Zhao,Xiaoqing Qian,Fei Pan,Chunlei Zhang,Yuming Yang,Jesús Martínez de la Fuente,Daxiang Cui

The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions (pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo–photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo–photodynamic system for theranostics of lung cancer, etc. in the near future.

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Materials Science & Engineering C-Materials for Biological Applications · 2016 · IF 3.42

Redox and pH dual-responsive PEG and chitosan-conjugated hollow mesoporous silica for controlled drug release

Jian Jiao,Xian Li,Sha Zhang,Jie Liu,Donghua Di,Ying Zhang,Qinfu Zhao,Siling Wang

In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions. The DOX loaded DOX/HMSN-SS-CS@PEG had a relatively high drug loading efficiency up to 32.8%. In vitro release results indicated that DOX was dramatically blocked within the mesopores of HMSN-SS-CS@PEG in pH 7.4 PBS without addition of GSH. However, the release rate of DOX was markedly increased after the addition of 10   mM GSH or in pH   5.0 release medium. Moreover, the release of DOX was further improved in pH   5.0 PBS with 10   mM GSH. The HMSN-SS-CS@PEG could markedly decrease the hemolysis percent and protein adsorption, and increase the biocompatibility and stability of HMSN compared with the HMSN-SS-CS and bare HMSN. This work suggested an exploration about HMSN based stimuli-responsive drug delivery and these results demonstrated that HMSN-SS-CS@PEG exhibited dual-responsive drug release property and could be used as a promising carrier for cancer therapy.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ChemPlusChem · 2016 ·Vol. 81 ·期 6 ·541-549 · IF 2.836

A pH-Responsive Soluble-Polymer-Based Homogeneous Ruthenium Catalyst for Highly Efficient Asymmetric Transfer Hydrogenation (ATH)

Yinzheng Xie,Mengpan Wang,Xiaohui Wu,Chen Chen,Wenbo Ma,Qifeng Dong,Mingming Yuan,Zhenshan Hou

Graphical Catalytic converter : A pH-responsive polymer catalyst was synthesized by the copolymerization of dimethyl aminopropyl acrylamide and N - p -styrenesulfonyl-1,2-diphenylethylenediamine, followed by coordination with Ru complexes (see figure). The catalyst was highly efficient for asymmetric transfer hydrogenation of a wide range of substrates and was recycled easily by means of pH-induced precipitation. A pH-responsive polymer has been synthesized successfully by means of copolymerization of dimethyl aminopropyl acrylamide (DMAPA) and N - p -styrenesulfonyl-1,2-diphenylethylenediamine (V-TsDPEN). The pH-responsive polymer coordination ruthenium complex was thus prepared and employed as an efficient catalyst for the asymmetric transfer hydrogenation (ATH) of various ketones. The polymer catalyst exhibited an attractive pH-induced phase-separable behavior in water: it could be dissolved in water when the pH of the solution was lower than 6.5 at the beginning of the reaction, but was precipitated completely from water when the pH of the solution was above 8.5 after reaction. Additionally, the catalysts were highly efficient for the ATH of a wide range of substrates that bore different functional groups and could be recycled easily from the aqueous solution by means of self-separation. They could be recycled eight times without significant changes in catalytic activity and enantioselectivity.

CAS / MDL: 5205-93-6 25704-18-1
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RSC Advances · 2016 ·Vol. 6 ·期 47 ·40991-41001 · IF 3.289

A facile strategy to fabricate covalently linked raspberry-like nanocomposites with pH and thermo tunable structures

Ruiwei Guo,Xing Chen,Xiaolei Zhu,Anjie Dong,Jianhua Zhang

The preparations of covalently linked raspberry-like composite particles often suffer from uncontrolled particle shape and surface morphology, tedious reactions to introduce surface reactive groups, inefficient inter-particle reactions, and rigorous requirements for the formation of hierarchical structure. In this study, we developed a facile strategy to fabricate a kind of size-controlled, positively charged, alkoxysilanes-functionalized nanoparticles (Tsi-PDMAEMA-PSt NPs) via a combination of the ability of RAFT polymerization to design macromolecular architectures and the process of polymer self-assembly to produce well-defined NPs. Tsi-PDMAEMA-PSt NPs can effectively deposit on the outer surface of negatively charged silica microspheres and then form stable silica@polymer particles by the reaction between alkoxysilanes and surface silanols. The surface morphology, particle size, ζ-potential, structure stability as well as pH and thermo-responsiveness of the prepared composite particles were investigated. The results indicated that the prepared silica@polymer particles possessed unique raspberry-like surface structures with high stability and controllability. Moreover, the surface morphology and dispersion state of silica@polymer particles in water can respond to the change of pH and temperature. Consequently, considering the high simplicity and controllability, the design herein provided a promising route to prepare the long-stable raspberry-like composite microspheres with unique surface morphologies and stimuli-responsive properties for a wide range of possible applications.

CAS / MDL: 78-67-1
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