RSC Advances
·
2019
·Vol. 9
·期 27
·15196-15204
·
IF 3.049
Yun Hong,Dongsen Mao,Rui Wu,Zhe Gao,Tingting Meng,Rongrong Wang,Lin Liu,Jing Miao
DNAzymes have the potential to suppress gene expression through sequence-specific mRNA cleavage and can therefore play an important role in various gene therapies. Hepatitis B virus (HBV) is still one of the most serious liver infections in people around the world and is difficult to treat. We previously designed a 10-23 DNAzyme called DrzBS, which targets HBV S gene expression, but this enzyme depends on exogenous delivery, and so its application has been limited. To overcome this limitation, we have now developed a chitosan-based nanocarrier (chitosan-g-stearic acid, CSO–SA) for intracellular delivery of DrzBS, then compared the inhibition effect of our CSO–SA/DrzBS complex to a common transfection reagent, Lipofectamine™ 2000/DrzBS, on hepatitis B surface antigen expression. The synthesized CSO–SA assembles into micelles in an aqueous solution and exhibits excellent cytoplasmic targeting, and could protect DrzBS from degradation by ribonuclease. CSO–SA/DrzBS showed a higher inhibition rate (IR) than Lipofectamine™ 2000/DrzBS. Moreover, at the same DrzBS concentration (1.2 μmol L−1), the maximum IR of CSO–SA/DrzBS micelles was 2.4-fold that of the Lipofectamine™ 2000/DrzBS complex, and held on for 96 hours. Compared with Lipofectamine™ 2000/DrzBS, CSO–SA/DrzBS achieved a higher HBV inhibition effect. This study demonstrates that CSO–SA micelles can serve as a potential vector for DrzBS and that CSO–SA/DrzBS micelles are a promising application for anti-HBV gene therapy.
研究领域:
医学
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分子生物学
·
基因治疗
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DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2018
·
IF 4.485
Xiaolong Zhang,Mingkui Zhang,Mingqi Wang,Han Peng,Qi Hua,Liwei Ma,Baoyan Wang,Hua Wei
Polymeric prodrugs with precisely controlled drug loading content (DLC) and rapid intracellular destabilization generally require complicated chemistry that hinders large-scale manufacture. For this purpose, we reported in this study a facile construction of reduction-sensitive amphiphilic polyprodrugs with an anticancer drug, 10-hydroxycamptothecin (HCPT), and a hydrophilic poly(ethylene oxide) (PEG) moiety as the alternating building blocks of the multiblock copolymer using Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAc) click coupling between azide-SS-HCPT-SS-azide and alkyne-PEG-alkyne. Adoption of PEGs with two different molecular weights (MWs) of 400 and 1450 Da (PEG400 and PEG1450) afforded two polyprodrugs with different DLCs. Both formulations can self-assemble into spherical micelles with hydrodynamic diameter smaller than 200 nm, and exhibit glutathione (GSH)-triggered degradation for promoted drug release. A further comparison study revealed that the PEG1450-based polyprodrug is a better formulation than the analogue constructed from PEG400 in terms of in vitro drug release behaviors, and cytotoxicity. This work thus provides a facile yet efficient strategy toward polymeric prodrugs with precisely controlled DLC and reduction-triggered degradation for enhanced anticancer drug delivery.
研究领域:
药学
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高分子化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2015
·Vol. 7
·期 3
·468-483
·
IF 3.681
Dongjian Shi,Jinting Hua,Li Zhang,Mingqing Chen
Novel bio-based aliphatic copolyesters, poly(lactic acid-co-10-hydroxy decanoate) (P(LA-co-HDA), PLH), were successfully synthesized from lactic acid (LA) and 10-hydroxycapric acid (HDA) by a thermal polycondensation process, in the presence ofp-toluenesulfonic acid (p-TSA) and SnCl2·2H2O as co-catalyst. The copolymer structure was characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1H NMR). The weight average molecular weights (Mw) of PLH, from gel permeation chromatography (GPC) measurements, were controlled from 18,500 to 37,900 by changing the molar ratios of LA and HDA. Thermogravimetric analysis (TGA) results showed that PLH had excellent thermal stability, and the decomposition temperature at the maximum rate was above 280 °C. The glass transition temperature (Tg) and melting temperature (Tm) of PLH decreased continuously with increasing the HDA composition by differential scanning calorimetry (DSC) measurements. PLH showed high ductility, and the breaking elongation increased significantly by the increment of the HDA composition. Moreover, the PLH copolymer could degrade in buffer solution. The cell adhesion results showed that PLH had good biocompatibility with NIH/3T3 cells. The bio-based PLH copolymers have potential applications as thermoplastics, elastomers or impact modifiers in the biomedical, industrial and agricultural fields.Keywords:bio-based copolymer;poly(lactic acid);poly(10-hydroxycapric acid);high performance;mechanical properties
研究领域:
材料科学
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生物医学工程
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高分子化学
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DOI
高影响因子
Chemistry-An Asian Journal
·
2019
·Vol. 15
·期 15
·2341-2345
·
IF 3.698
Junjun Hou,Meihuizi Jiang,Xiao He,Pengchao Liu,Chang Long,Lian Yu,Zhiwei Huang,Jin Huang,Lianshan Li,Zhiyong Tang
Graphical A sub-10 nm polyamide nanofiltration membrane was synthesized through interfacial polymerization due to the extremely low solubility of the ethidium bromide monomer in organic phase, which strictly limits the polymerization process at the interface of the water and hexane. Thanks to the ultrathin thickness, these membranes show excellent water permeance and high dye rejection. To separate small molecules from the solvent with high permeability and selectivity, the membrane process is thought to be highly effective with much lower energy consumption when compared to the traditional thermal-based separation process. To achieve high solvent permeance, a sub-10 nm thick polyamide nanofiltration membrane was synthesized through interfacial polymerization of ethidium bromide (EtBr) and trimesoyl chloride (TMC). Thanks to the extremely low solubility of the EtBr monomer in the organic phase, the polymerization process was strictly limited at the interface of the water and hexane, leading to an ultrathin polyamide membrane with a thickness down to sub-10 nm. When used in nanofiltration, these ultrathin membranes display ultrafast water permeation of 40 liter per square meter per hour per bar (L m −2 h −1 bar −1 ), and a high Congo red rejection rate of 93 %. This work demonstrates a new route to synthesize ultrathin polyamide membranes by the traditional interfacial polymerization.
研究领域:
化学工程
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材料科学
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环境科学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR MATERIALS AND ENGINEERING
·
2021
·Vol. 307
·期 1
·2100539
·
IF 4.367
Zhaojie Yang,Minghua Zhang,Zhixin Zhao,Xi Zhang,Minmin Fan
The quaternized polysulfone/polyquaternium-10 (QPSU/PQ-10) anion exchange membranes (AEMs) with a semi-interpenetrating network are prepared by the simple solution casting method. The effects of the mass ratio of chloromethylated polysulfone (CMPSU) to PQ-10 and the molar ratio of quaternized chloromethyl (QCM) to cross-linked chloromethyl (CCM) on the performance of AEM are systematically investigated. The results show that the introduction of PQ-10 endows the QPSU/PQ-10 AEM with excellent mechanical performance. More specifically, the QPSU/PQ-10 AEM has moderate water uptake, swelling ratio, and ion exchange capacity (IEC) at an appropriate composition ratio and crosslinking degree. In particular, the tensile strength and elongation at break of the QP0.5-1 membrane with the optimal composition ratio and crosslinking degree are 23.63 MPa and 20.07%, respectively; and its ion conductivity is up to 69.91 mS cm −1 at 80 °C. Furthermore, the peak power density of the single fuel cell assembled from the QP0.5-1 membrane is 75.64 mW cm −2 at 60 °C. Herein, the QPSU/PQ-10 AEM has good thermal oxidation stability, mechanical properties, and ion conductivity, highlighting the potential of bio-based PQ-10 as an ion-conducting functional molecule in AEMs.
研究领域:
材料科学
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燃料电池技术
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DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2015
·Vol. 11
·期 4
·711-721
·
IF 5.338
Yang Linjie,Jiang Jizong,Hong Jingyi,Di Jing,Liao Yonghong,Kuang Haixue,Wang Xiangtao
The objective of this study was to evaluate the feasibility of producing 10-hydroxycamptothecin nanosuspensions with high drug payload and to then determine the in vitro and in vivo characteristics of these nanosuspensions. Using cholesterol-PEG600 as a stabilizer, 10-hydroxycamptothecin
nanosuspensions were successfully prepared using a precipitation-combined high-pressure homogenization method. A satisfactory drug payload of 90.39% (w/w) was achieved. The obtained nanosuspensions were spherical, with a mean particle size of 115.0 ± 0.4 nm, and they were monodisperse
with a polydispersity index of 0.134 ± 0.001. The 10-hydroxycamptothecin remained in the same crystalline form in both the nanosuspensions and the bulk powder. In vitro, the 10-hydroxycamptothecin nanosuspensions released the encapsulated drug with nearly zero-order kinetics,
and the accumulative release reached 90% within 72 hours. In vitro cytotoxicity assay showed that the 10-hydroxycamptothecin nanosuspensions had significantly enhanced cytotoxicity against HepG2 cells compared to the commercially available 10-hydroxycamptothecin injections. The in
vivo study with H22 tumor-bearing mice and intravenous injection of the drug showed that in contrast to the 10-hydroxycamptothecin injections, the 10-hydroxycamptothecin nanosuspensions exhibited significantly enhanced biodistribution, particularly in the lung (393.40-fold AUC0–24
h, liver (192.35-fold AUC0–24 h, spleen (141.67-fold AUC0–24 h and tumor (64.21-fold AUC0–24 h. The 10-hydroxycamptothecin nanosuspensions also showed improved antitumor therapeutic efficacy over the injections (89.83% vs. 30.56%). This
suggests that cholesterol-PEG600 may be an effective stabilizer for the preparation of hydrophobic drug nanosuspensions and that 10-hydroxycamptothecin nanosuspensions are a promising drug delivery system for tumor treatment.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF SOLID STATE ELECTROCHEMISTRY
·
2018
·Vol. 22
·期 8
·2405-2412
·
IF 2.509
Mo Zunli,Niu Xiaohui,Gao Huhu,Li Zhenliang,Meng Shujuan,Guo Ruibin
A novel and simple chiral sensing platform had been successfully fabricated by means of amidation reaction between 3, 4, 9, 10-perylenetetracarboxylic acid (PTCA) and chitosan (CS) to form 3, 4, 9, 10-perylenetetracarboxylic acid–chitosan (PTCA–CS) composite film. Since CS has chiral center and PTCA has excellent electrical conductivity, the PTCA–CS composite modified glassy carbon electrode (PTCA–CS/GCE) could be treated as an effective electrochemical chiral sensor and applied for chiral discrimination of tryptophan (Trp) enantiomers theoretically. PTCA–CS composite was characterized by Fourier transform infrared (FTIR) spectroscopy and cyclic voltammetry (CV). When the prepared chiral sensing interface interacted with tryptophan isomers, a higher selectivity was received from D-Trp by differential pulse voltammetry (DPV). It indicated that the PTCA–CS/GCE can be treated as an electrochemical chiral sensor for the discrimination of Trp enantiomers. Further study demonstrated that the peak currents were linearly increased with the increasing percentage of L-Trp of Trp racemic mixture. Furthermore, the enantioselective interaction of the PTCA–CS/GCE was systematically studied by other experimental factors, such as the incubation time and acidity.
研究领域:
生物化学
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分析化学
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材料科学
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产品关联
DOI
高影响因子
THERMOCHIMICA ACTA
·
2017
·
IF 2.236
Ying Zhang,Shi Zhang,Sanguo Peng,Maogang He
Diffusivity of redox shuttle additive in solvent plays an important role in the design of Li-ion battery. As redox shuttle additive, 10-methylphenothiazine (MPT) can give good overcharge protection in LiFePO4-based Li-ion cells, therefore diffusion coefficient of MPT in solvent needs to be known. A different data processing method based on optical digital interferometry is put forward to determine diffusion coefficient in this work. This method is verified by KCl aqueous solution and the relative standard uncertainty of diffusion coefficient is about 2.3%. The diffusion coefficients of MPT in dimethyl carbonate (DMC) from 288.15 K to 313.15 K at several concentrations are measured and the corresponding calculation equation of diffusion coefficient is presented.
研究领域:
化学工程
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电化学
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材料科学
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产品关联
DOI
高影响因子
JOURNAL OF RARE EARTHS
·
2023
·
IF 4.9
Aoyang Sha,Huifang Yang,Zhengyan He,Zhigao Xu,Chenjie Wu,Wu Ming,Ru'an Chi
To solve the problems of the long development period, low mass transfer efficiency and high impurity content in the in-situ leaching process of weathered crust elution-deposited rare earth ores (WCE-DREO), cationic hydroxyethyl cellulose (PQ-10) was composited with conventional leaching agent ammonium sulfate ((NH 4 ) 2 SO 4 ) to form a novel composite leaching agent. The effects of PQ-10 concentration, leaching temperature and leaching flow rate of the composite leaching agent on the leaching kinetics and mass transfer processes of rare earth (RE) and aluminum (Al) were investigated. Compared to the single leaching agent (NH 4 ) 2 SO 4 , the composite leaching agent (2 wt% (NH 4 ) 2 SO 4 +0.02 wt% PQ-10) can reduce the RE leaching equilibrium time from 465 to 130 min and increase the RE leaching efficiency and decrease the Al leaching efficiency. It also facilitates the leaching process of WCE-DREO by increasing the peak concentrations of RE and Al, reducing the theoretical tower plate height (HETP) and improving the leaching mass transfer efficiency. It is indicated that PQ-10 can promote the leaching of WCE-DREO. The leaching process of the composite leaching system conforms to the diffusion kinetic control model. When the PQ-10 concentration is in the range of 0.005 wt% – 0.020 wt%, the reaction orders of RE and Al are 0.73 and 0.54, respectively, which shows a positive effect on the leaching velocity; when the PQ-10 concentration is in the range of 0.030 wt% – 0.060 wt%, the reaction orders of RE and Al are – 1.16 and – 0.75, respectively, which show a negative effect on the leaching velocity. In the range of 10 – 50 °C, the apparent activation energies of RE and Al are 15.02 and 17.31 kJ/mol, respectively, and the higher the leaching temperature, the smaller the HETP and the higher the leaching velocity and mass transfer efficiency. The increase in leaching flow rate contributes to the increase in the longitudinal diffusion velocity of the leaching agent within WCE-DREO, causing a shorter time for RE and Al to reach leaching equilibrium. In addition, the flow rate and HETP are consistent with the Van Deemter equation. At a flow rate of 0.8 mL/min, HETP was minimized and the optimal mass transfer efficiencies is achieved for RE and Al.
研究领域:
冶金工程
·
化学工程
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Linjie Yang,Jingyi Hong,Jing Di,Yifei Guo,Meihua Han,Meifeng Liu,Xiangtao Wang
In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG1000-HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG1000-HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC50 value against HepG2 cells and 14.1 times lower IC50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG1000-HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy.
研究领域:
药剂学
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肿瘤学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Qingye Meng,Shuangling Zhong,Jia Wang,Yan Gao,Xuejun Cui
Controlled and accurate drug release at the target site have been the focus of research. Especially in cancer therapy, economical, convenient and accurate delivery strategies could help to reduce the toxic effects of drugs on normal tissues and improve drug availability. In the study, glutathione (GSH)-responsive microcapsules (FA-RSMCs) were prepared by sonochemical method based on thiolated modified starch . 10-Hydroxycamptothecin (HCPT) was designed as a reactive oxygen species (ROS)-responsive polyprodrug (polyHCPT), which was loaded into the core of the microcapsules to obtain stepwise released drug delivery carriers. In the tumor microenvironment, FA-RSMCs first triggered GSH-responsive cleavage to release polyHCPT, followed by ROS-responsive cleavage of polyHCPT to release intact HCPT drug molecules. The results of experiments in simulated tumor microenvironment showed that FA-RSMCs exhibited good cascade-response release properties in vitro . It exhibited good anti-tumor ability and protection of normal cells in cytotoxicity in vitro . This strategy enhanced the accuracy and safety of targeted delivery of HCPT via microcapsules, which has potential for clinical application.
研究领域:
药剂学
·
肿瘤学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
RSC Medicinal Chemistry
·
2024
·
IF 4.1
Ji-Chao Guo,Shi-Hui Deng,Shu-Min Zhou,Xuan Zhou,Jiajia Du,Si-Han Zhou,Qi-Hua Zhao,Zhong-Yan Cai,Xiaoxia Ren,Ming-jin Xie
There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 μg mL−1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer.
研究领域:
药学
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）