ACS Applied Bio Materials
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2019
·
IF 0
Ying Zhang,Hongyue Zhang,Xiang Qin,Chen Yang,Zhiqiang Wang,Yingxue Jin
Targeted delivery of photosensitizer for antitumor photodynamic therapy has received much attention recently. In this research, a multitargeting graphene oxide (GO) nanosystem (GFFP-TPPa) was fabricated based on the magnetically targeted nano-Fe3O4, active targeted folic acid (FA), and mitochondria-targeted triphenylphosphine, aiming to provide an effective drug delivery system of photosensitizer for improved photodynamic therapy against human tumor. The effective photosensitizer release from GFFP-TPPa under mild acidic pH condition (such as tumor microenvironment) suggested our designed nanosystem could reduce cutaneous phototoxicity of nanoparticles (NPs) in normal cells environment, which was further verified by the observation that the fluorescence of GFFP-TPPa was significantly quenched compared with free PPa. Research of cellular morphological variation, uptaking test, and intracellular single oxygen detection has validated the effectiveness of GFFP-TPPa NPs against tumor cells and potential fluorescence imaging function. Moreover, GFFP-TPPa NPs have excellent superparamagnetic properties and FA-targeted property of NPs, which was verified by the tumor cellular uptake of GFFP-TPPa. Finally, the precise deliver of photosensitizer to mitochondria has been proved by Mito-Tracker Green organelle localization. Our research indicated that the fabricated nanosystem could be applied conveniently for PDT based on multitargetability.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
·
IF 4.784
Yuan Li,Yubin Ying,Yaqi Zhou,Yujun Ge,Chunhong Yuan,Chunhua Wu,Yaqin Hu
The goal of the study is to develop a novel pH-indicating intelligent packaging by using purple potato extractions (PPE), chitosan and surface-deacetylated chitin nanofibers (CN). Since the major pH-sensitive pigment of PPE was anthocyanin (24.3 mg/g), whether anthocyanins could be loaded on a solid phase to prevent its color fading was further tested. The results of Fourier transform infrared spectrophotometry (FT-IR) and differential scanning calorimetry (DSC) indicated that PPE was efficiently attached into the chitosan film. Meanwhile, adding CN (0.450%, w/v) into chitosan film could significantly enhance the tensile strength (TS), the water-resistant ability and the roughness of chitosan film. Whereas higher content of CN (0.600%, w/v) did not further improve mechanical properties and CN would distribute unevenly due to aggregation in the films. In addition to pH-indicating ability, CS-CN-PPE exhibited the extraordinary antioxidant activities and this provides another advantage of packaging readily oxidizable substances. Taken together, the current study provided a novel and biocompatible packaging with strengthened mechanical property and intelligent pH indicator.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Bailong Tao,Yiman Deng,Liying Song,Wenwen Ma,Ying Qian,Chuanchuan Lin,Zhang Yuan,Lu Lu,Maowen Chen,Xin Yang,Kaiyong Cai
Bacterial infection and surface biointertness are two main causes for titanium (Ti)-based orthopedic implants failure. To improve the antibacterial ability and enhance poor osteogenic property of Ti substrates, in this work, we employed titania nanotubes (TNTs) as Bone Morphogenetic Protein 2 (BMP2) carrier, and a pH-responsive multilayer film composed of alginate dialdehyde-gentamicin (ADA-Gen) and chitosan (Chi) was constructed onto BMP2-loaded TNTs substrates through layer-by-layer (LBL) assembly technique, resulting in TNT-BMP2-LBLg samples. The release experiments revealed that acidic environment could trigger the release of Gen from the multilayer films and in turn accelerate the release of BMP2 from TNTs. Moreover, antibacterial assay against E. coli and S. aureus confirmed that the TNT-BMP2-LBLg had excellent antibacterial capacity both in early (6 h) and in long-term (72 h). Meanwhile, in vitro cellular tests demonstrated that TNT-BMP2-LBLg had good cytocompatibility toward osteoblasts even co-cultured with S. aureus . Importantly, the obtained TNT-BMP2-LBLg promoted differentiation of osteoblasts, including enhanced alkaline phosphatase activity, improved mineralization capability and stimulated osteogenic-relative gene expression. This study thus provides a promising strategy to develop pH-responsive antibacterial and enhance bone integrative Ti-based implants for potential orthopedic application.
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GREEN CHEMISTRY
·
2019
·Vol. 21
·期 5
·1141-1151
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IF 9.405
Cheng Cai,Yu Bao,Xuejuan Zhan,Xuliang Lin,Hongming Lou,Yuxia Pang,Yong Qian,Xueqing Qiu
The conversion of lignocelluloses into fermentable sugars by enzymatic hydrolysis is a key step in biorefining. However, there are still some bottleneck problems such as low hydrolysis efficiency, high cost of cellulase and low utilization of lignin. In this work, the nonionic surfactant monomethoxy polyethylene glycol (MPEG) was grafted on enzymatic hydrolysis lignin (EHL) to obtain a pH-responsive polymer (EHL-MPEG). EHL-MPEG could achieve rapid dissolution–precipitation conversion by the ionization and protonation of carboxyl groups. By adjusting the grafting amount of MPEG, EHL-MPEG could not only enhance the enzymatic hydrolysis of lignocelluloses, but also efficiently recover cellulase after hydrolysis. Adding 3 g L−1 EHL-MPEG40 (the mass ratio of MPEG to EHL was 40%) could increase the glucose yield of corncob residue (CCR) and pretreated eucalyptus from 79.4% and 48.3% to 92.5% and 89.5%, respectively, which was comparable to the effect of the nonionic surfactant PEG4600. By simply adjusting the pH of solutions, more than 85% of cellulase proteins could be recovered by EHL-MPEG40 with almost complete recovery of β-glycosidase, exoglucanase V and xylanase. Compared with a pH-responsive lignin amphoteric surfactant (pH-LAS) obtained by grafting ionic groups on lignin, EHL-MPEG40 had a more sensitive pH response and a stronger cellulase recovery ability. In the enzymatic hydrolysis of CCR, a pH-LAS could save about 50% of cellulase, while EHL-MPEG40 could save more than 60% of cellulase. Furthermore, approximately 96% of EHL-MPEG40 could be reused. This new method can not only evade the process of immobilization, but also avoid the activity loss and component change of cellulase through immobilization. Using recyclable EHL-MPEG to improve glucose yield and recover cellulase during lignocellulosic hydrolysis is of great significance for improving the enzymatic saccharification process, reducing the cost of cellulase and realizing comprehensive utilization of lignocelluloses.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2019
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IF 3.532
Zheng Zhao,Weihe Yao,Ning Wang,Chenyu Liu,Hengjun Zhou,Hailiang Chen,Weihong Qiao
Cationic lipids can easily assemble into spherical liposomes in aqueous phase which showed unique superiority in drug and gene delivery. However, the toxicity of cationic lipids is still an obstacle to application. To develop low toxicity cationic lipids, we designed two cationic lipids contained different number of hydroxyl groups . Biocompatible mono-hydroxyl and multi-hydroxyl galactose head group was respectively modified to a biodegradable quaternary amine lipid, and two novel hydroxyl cationic lipids were synthesized and characterized by MS, 1 H NMR and 13 C NMR. Two lipids showed good surface activity and both of them can assemble to about 80 nm stable small unilamellar vesicles (SUVs) with cholesterol in aqueous phase. Both of lipids showed relatively lower toxicity than the well-known cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). In vitro 24 h IC 50 of two assemblies were more than 50 μg/mL, which were about 10 μg/mL higher than the IC 50 of DOTAP. Multi-hydroxyl galactose lipids group showed much lower toxicity than mono-hydroxyl lipids group. Moreover, Both of the assemblies with lower hemolysis were nearly non-hemolytic risk under the concentration of 30 μg/mL. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that the average sizes of both doxorubicin (DOX) loaded liposomes were about 110 nm. The DOX entrapment efficiencies of galactose liposome and mono-hydroxyl liposome were 58% and 91%, respectively. Both of the DOX loaded liposomes were stable after one month placed at room temperature. Two DOX loaded liposomes showed better anti-cancer effect than free DOX above 5 μg/mL, and they can be internalized into cells and produce more release of DOX inside MCF-7 cells and HepG2 cells at pH 5.0. These results suggested that synthesized lipids are suitable as potential low toxicity cationic drug delivery systems .
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 43
·期 34
·13363-13370
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IF 3.069
Weifen Niu,Juan Jia,Junkai Li,Chao Zhang,Keming Yun
The lysosome is known to be an acidic organelle that is ubiquitous in cells. Acidic pH is a characteristic feature of lysosomes, and aberrant lysosomal pH values have been manifested to be associated with diverse diseases. In order to monitor the lysosomal pH changes, we developed a ratiometric emission NIR-fluorescent probe (CzQl) for the quantitative analysis of the lysosomal pH in living cells and in vivo. CzQl was constructed via the ethylene bridging of carbazole derivatives and quinoline. The protonation of the probe resulted in a marked green-to-red emission color change. The probe exhibited an ideal pKa value of 4.60 with a linear relationship in the pH range of 3.9–5.3, which covered most of the pH ranges of lysosomes, and was useful for the quantitative detection and imaging of lysosomal pH changes. Moreover, CzQl exhibited easy loading capability, high selectivity, a large Stokes shift, specific lysosome-targeting ability and low cytotoxicity; thereby, it was successfully used for monitoring the lysosomal pH changes at a cellular level as well as the LPS-mediated inflammation in vivo.
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JOURNAL OF CONTROLLED RELEASE
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2019
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IF 7.901
Jean Felix Mukerabigwi,Wei Yin,Zengshi Zha,Wendong Ke,Yuheng Wang,Weijian Chen,Abd Al-Wali Mohammed Mohammed Japir,Yi Wang,Zhishen Ge
Therapeutic nanoreactors are currently emerging as promising nanoplatforms to in situ transform inert prodrugs into active drugs. Nevertheless, it is still challenging to engineer a nanoreactor with balanced key features of tunable selective membrane permeability and structural stability for prodrug delivery and activation in diseased tissues. Herein, we present a facile strategy to engineer a polymersome nanoreactor with tumor-specific tunable membrane permeability to load both hydrophobic phenylboronic ester-caged anticancer prodrugs ( e.g. , camptothecin or paclitaxel prodrug) and hydrophilic glucose oxidase (GOD) in the membranes and cavities, respectively. The nanoreactors maintain inactive during blood circulation and in normal tissues. Upon accumulation in tumors, the mild acidic microenvironment triggers selective membrane permeability to allow small molecules (glucose and O 2 ) to diffuse across the membrane and react under the catalysis of GOD. The massively generated H 2 O 2 triggers in situ transformation of innocuous prodrugs into toxic parental drugs through cleavage of the self-immolative degradable caging groups. The developed system showed significantly enhanced antitumor efficacy by H 2 O 2 production and prodrug activation via combined oxidation-chemotherapy. The well-devised polymersome nanoreactors with tumor-pH-tunable membrane permeability to coload H 2 O 2 -responsive prodrug and GOD represent a novel strategy to realize prodrug delivery and activation for enhanced therapeutic efficacy with low side toxicity.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Jing Qu,Si Peng,Rui Wang,Sheng-tao Yang,Qing-han Zhou,Juan Lin
The short blood circulation time, reduced cellular uptake, and uncontrollable drug release still hinder the polymer micelle as an efficient drug delivery vehicle in clinical applications. In this study, a series of stepwise pH-sensitive and biodegradable polypeptide hybrid terpolymers, poly (lysine- co - N,N -bis(acryloyl) cystamine- co -dimethylmaleic anhydride) (PLB-DMMA), were designed and synthesized to achieve prolonged circulation time, enhanced cellular uptake and controllable anti-cancer drug release. The synthesized terpolymers can self-assemble into spherical nano-micelles (NMs) with narrow distributions and exhibited stepwise responses to extracellular and intracellular pH condition of the tumor cell. The as prepared NMs showed a negative surface charge under normal physiological conditions exhibiting advantageous stability during blood circulation. By the first-step pH response, the surface charge of the NMs switched from negative to positive to enhance cellular uptake under the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response resulted in an endosome escape of the NMs via the “proton-sponge” effect in the acidic endo/lysosome environment. Additionally, a rapid drug release was triggered in response to the intracellular reductive environment of tumor cells via the destruction of disulfide-linked polymer chains to enhance the nucleus delivery of DOX. in vitro cell assays showed that the blank NMs showed negligible systemic toxicity against normal cells while the DOX-loaded NMs significantly inhibited growth of the tumor cells. In general, it was suggested that the as developed stepwise pH-sensitive and biodegradable PLB-DMMA based NMs would be a smart and promising drug delivery candidate for anti-cancer chemotherapy.
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JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY
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2019
·
IF 1.479
Foster Dodzi Gomado,Yanling Wang,Forson Kobina,Caili Dai,Augustus Owusu-Boadi
An experimental investigation was conducted to evaluate the impact of silica nanoparticles concentration on a pH-responsive emulsion system in terms of its emulsification, phase inversion mechanisms and long-term stability. Also, the adsorption studies of the pH-responsive emulsifier and the nanoparticles were evaluated in order to comprehend the synergism between the nanoparticles and the emulsifier. The sorption of the emulsifier onto the surfaces of the nanoparticles caused wettability alteration enabling the nanoparticle to act as nanocomposite emulsifier. It was found out that the emulsions undergoes phase inversion upon treating it with a minimum of 1 ml of 0.5 M HCl and also increasing the nanoparticles concentration had no noticeable effect on the phase mechanism, However, the nanoparticles cannot stabilized the O/W formed after the phase inversion. The presence of the nanoparticles improves the thermal stability of the reversible emulsion and also protects the emulsions against the presence of NaBr and otherwise for salts like NaCl and Na2SO4. These outcomes reveal the various properties of a pH-responsive emulsion which are affected by the presences of nanoparticles in order to fully control stimuli-responsive emulsions to our advantage.
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Environmental Science-Nano
·
2019
·Vol. 6
·期 12
·3699-3711
·
IF 7.704
Wenjing Ma,Mengjie Zhang,Yuansheng Li,Mengmeng Kang,Chaobo Huang,Guodong Fu
One of the most pervasive environmental issues is water contaminated with various oils. Developing an efficient and novel functional membrane for oil/water separation is urgently needed. Herein, a flexible, durable and magnetic pH-responsive F3O4/MA–TiO2/PI electrospun nanofibrous membrane (ENM) was fabricated via an electrospinning and green dip-coating route. Combining the rough hierarchical structure and pH-responsive wettability, the as-prepared hybrid membrane can controllably separate a range of not only heavy oil/water but also light oil/water mixtures by only adjusting the pH of the aqueous medium. Both separations exhibit a large flux and outstanding efficiency for the tested oil/water mixtures even after 20 reuse cycles due to the hierarchical structure and flexibility of the membrane. In addition, the flexibility and magnetism of the membrane make it easily removed with a magnet after the separation of the oil/water mixtures. More importantly, the as-prepared membrane not only has excellent stability towards high temperature, corrosive organic solvent/salt solution immersion, and UV irradiation but also shows great resistance to mechanical abrasion and ultrasonic treatment, and the preparation method is facile, environmentally friendly, and cost-effective. Thus, such a membrane may offer exciting opportunities in the application of oily wastewater treatment and on-demand oil/water separation.
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CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Jialu Gao,Yong Xu,Yan Zheng,Xin Wang,Shuting Li,Guoqing Yan,Jun Wang,Rupei Tang
A series of pH-sensitive carboxymethyl chitosan (CMCS) hydrogels were prepared via ortho ester linkage. DOX-loaded gelatin nanoparticles with an average diameter of around 50 nm were incorporated into hydrogels to obtain hybrid hydrogels (DOX-NPs-Gel), which could be locally implanted into tumor site in any shape. The physicochemical and mechanical properties of these hydrogels could be easily controlled by adjusting the proportion of crosslinking agent. DOX-NPs-Gel showed the pH-dependent degradation and drug release, and only 29.9% of DOX was released within 144 h at pH 7.4, while the cumulative release reached 49.3% and 65% at pH 6.5 and 5.0, respectively. In vivo study demonstrated that the implanted DOX-NPs-Gel efficiently improved DOX accumulation in tumor site through continuously degradation in mildly acidic environment of tumor tissues, and the tumor volume at the end of experiment was only 81.53 mm 3 , while tumor size reached to 229.22 mm 3 and 174.15 mm 3 after intravenous treatment with free DOX and DOX-NPs, respectively.
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CHEMISTRY-A EUROPEAN JOURNAL
·
2018
·Vol. 24
·期 52
·13830-13838
·
IF 5.16
Xiangming Li,Yihe Zhang,Zequn Ma,Meng Fu,Qi An
Graphical The heat is on : A facile and efficient approach for the preparation of pH responsive self-assembled (electrostatic interactions) rGO-polymer-DOX nanocomposites for photothermal and chemical therapy is reported (see figure). The development of well-controlled drug carriers that are stable and highly effective for the delivery of anticancer agents is challenging. Herein, we report a novel pH-controlled drug delivery system, utilizing reducing graphene oxide (rGO)-polymer self-assembly films as carriers, for the preparation of effective drug nanorods and nanoparticles. In this system, the rGO-polymer carriers were constructed by the alternating assembly of poly- l -lysine (PLL) and polyaspartic acid (PASP) around the rGO sheets. Furthermore, the rGO-polymer cores, which possess a positively charged surface as the desired template, could assemble with negatively charged doxorubicin (DOX) via electrostatic interactions. The DOX embedding efficiency and the morphology of the drug nanocomposites could be controlled by the number of rGO-polymer bilayers and concentration of the rGO-polymer bilayers and the initial DOX concentration. Importantly, the release of DOX could be regulated by controlling the pH and by using a NIR laser. Under acidic conditions, the interactions between the PASP layer and DOX molecules can be broken, resulting in gradual release of the DOX molecules. Upon NIR irradiation, the release of DOX could be further accelerated and a photothermal effect from rGO induced. Cellular uptake and cytotoxicity experiments indicate that the drug nanocomposites possess effective anticancer activity. Thus, in this work, we present a useful strategy for the fabrication of pH-responsive drug nanocomposites for combined photothermal and chemical therapy. The nanocomposite can be used as a potential drug delivery system for practical cancer treatment.
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