INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Yang Wang,Wenhui Zha,Ji Wang,Shuo Dong,Chao Liu,Yuhao Jiang,Xinsong Li
Chemodynamic therapy (CDT) has emerged as a powerful tumor treatment option by inducing the imbalance of redox homeostasis in cancer cells. Nevertheless, the therapeutic outcomes were greatly limited because of insufficient endogenous H 2 O 2 and upregulated cellular antioxidant defense in the tumor microenvironment (TME). Herein, a liposome-incorporated in-situ alginate hydrogel locoregional treatment strategy was developed, which involves using hemin-loaded artesunate dimer liposomes (HAD-LP) as redox-triggered self-amplified C-center free radical nanogenerator to enhance CDT. First, HAD-LP based on artesunate dimer glycerophosphocholine (ART-GPC) was prepared by a thin film method. Their spherical structure was manifested by dynamic light scattering (DLS) and transmission electron microscope (TEM). The generation of C-center free radicals from HAD-LP was carefully evaluated by using methylene blue (MB) degradation method. The results suggested that the hemin was reduced to heme under the action of glutathione (GSH), which could catalyze the breakage of endoperoxide of ART-GPC derived dihydroartemisinin (DHA) to generate toxic C-centered free radicals in a H 2 O 2 and pH-independent manner. Moreover, the change of intracellular GSH and free radical level was monitored through ultraviolet spectroscopy and confocal laser scanning microscope (CLSM). It was revealed that the hemin reduction induced GSH depletion and elevated free radical level, disrupting cellular redox homeostasis. After co-incubation with MDA-MB-231 or 4 T1 cells, HAD-LP was found to be highly cytotoxic. In order to prolong retention and improve antitumor efficacy, HAD-LP was mixed with alginate and injected intratumorally into 4 T1 tumor bearing mice. The injected HAD-LP and alginate mixture formed in-situ hydrogel and achieved best antitumor effect with the growth inhibition rate of 72.6%. Together, the hemin-loaded artesunate dimer liposome-incorporated alginate hydrogel possessed effective antitumor activity through redox-triggered C-center free radical generation induced apoptosis in a H 2 O 2 and pH-independent manner, which might be a promising candidate in the application of chemodynamic anti-tumor therapy.
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JOURNAL OF ALLOYS AND COMPOUNDS
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2023
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IF 6.2
Guang-Rui Xu,Xue Jiang,Tiantian Sun,Xinlin Wang,Bin Li,Zexing Wu,Haiyan Liu,Lei Wang
Water-electrolytic hydrogen production has attracted extensive attention due to it can fully utilize renewable energy sources and residual secondary energy, while the sluggish kinetics reaction rate seriously hinders the hydrogen evolution reaction (HER) progress. Herein, we reported a novel and simple precipitation-calcination method for the synthesis of Ru branched nanostructures on porous N-doping carbon nanosheets (Ru BCNNs/PNC NNSs) with rough surface and step and edge atoms. The overpotentials for Ru BCNNs/PNC NNSs are 33.4 mV, 81.3 mV, and 99.9 mV in acidic, alkaline, and neutral media, respectively, to achieve the current density of 10 mA cm −2 , indicating the superior HER performance over a wide pH range due to the unique rough surfaces and abundant of steps and edges atoms. Meanwhile, the Tafel slopes are 21.7 mV dec −1 , 111.1 mV dec −1 , and 104.7 mV dec −1 for Ru BCNNs/PNC NNSs in 1.0 M HClO 4 , 1.0 M KOH, and 1.0 M phosphate buffer solution (PBS, pH=7.0), respectively, much lower than that of commercial Pt/C catalysts with mass loading of 10 % from Macklin Inc. (Pt/C-MK). Furthermore, due to the advantages of the strong interface binding energy between Ru and N-C, the Ru BCNNs/PNC NNSs show outstanding durability for HER not only in mild conditions but also in harsh conditions, outperforming most Ru-based electrocatalysts reported previously.
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Journal of Materials Chemistry B
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2023
·Vol. 11
·期 15
·3373-3386
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IF 7
Jiru Miao,Xiang Wu,Yue Fang,Mingzhu Zeng,Zhimao Huang,Mi Ouyang,Rong Wang
Catheter-associated urinary tract infections are one of the most common hospital-acquired infections. Encrustation formation results from infection of urease-producing bacteria and further complicates the situation. A typical sign of the initial onset of encrustation formation is the alkalization of the urine (pH up to 9–10). However, effective antibacterial strategies with high antimicrobial loading efficiency and pH-responsiveness of antimicrobial release are still lacking. In this study, we developed a poly(sulfobetaine methacrylate)-tannic acid (polySBMA-TA) hydrogel coating, which served as a universal, efficient, and responsive carrier for antimicrobials on urinary catheters. Common antimicrobials, including poly(vinylpyrrolidone)-iodine, copper ions, and nitrofurazone were loaded into the polySBMA-TA coating in high efficiency (several fold higher than that of the polySBMA coating), via the formation of multiple non-covalent interactions between the antimicrobials and hydrogel coating. The hydrogel coatings maintained good antibacterial properties under neutral conditions. More importantly, the pH-responsive release of antibacterial agents under alkaline conditions further enhanced the antibacterial activity of the coatings, which was advantageous for killing the urease-producing bacteria and preventing encrustation. In vitro and in vivo tests confirmed that the hydrogel coating has good biocompatibility, and could effectively inhibit bacterial colonization and encrustation formation. This study offers new opportunities for the utilization of a simple and universal antimicrobial-loaded hydrogel coating with smart pH-responsive properties to combat bacterial colonization and encrustation formation in urinary catheters.
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JOURNAL OF CHROMATOGRAPHY A
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2023
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IF 4.1
Nasir Ali,Juan Qiao,Li Qi
Stimuli-responsive block copolymers have exhibited their feasibility for drug delivery and analysis of biomolecules. However, study of the electrophoretic behavior of antibiotics by open tubular capillary electrochromatography (OT-CEC) based on smart block copolymers coatings is still a substantial challenge. Herein, we reported an OT-CEC protocol for analysis of cephalosporin antibiotics with pH-responsive block copolymers as coatings. By using the reversible addition-fragmentation chain-transfers radical polymerisation technique, the smart poly(styrene-maleic anhydride-acrylic acid) (P(St-MAn-AA)) was synthesized and subsequently chemical bonded onto the inner walls of amino-grafted capillaries. The pH induced changes in the stretch/curl states of P(St-MAn-AA) chains were used to generate an adjustable hydrophobic/hydrophilic interaction and hydrogen bonds between the polymer coatings and the analytes. The OT-CEC performance was evaluated by varying the monomer ratios, polymer coating amounts and layers, buffer concentrations and pH values. Baseline separation of the three-test antibiotics was achieved at pH 8.0. The proposed OT-CEC technique was further applied to the determination of rat serum antibiotics in the metabolic processes. The present work demonstrates an enhancement in antibiotics separation efficiency, and shows a great potential for the preparation of stimuli-responsive block copolymers coatings and in OT-CEC analysis of real samples in living bio-systems.
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Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-17
·
IF 11.3
Huang Xueyan,Chen Fei,Ma Yeshuo,Zheng Fan,Fang Yanpeng,Feng Bin,Huang Shuai,Zeng Hongliang,Zeng Wenbin
Background Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization.Methods We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo.Results ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish.Conclusion sASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research.Graphical Abstract
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Journal of Environmental Chemical Engineering
·
2023
·
IF 7.7
Yubin Xiang,Jie Li,Ke Wang,Yangfan Zhang,Zhengyu Li,Zhi Li,Xue Lu,Yongming Guo
Nanocomposites have gained extensive interest in improving control efficacy and reducing usage amount of traditional pesticides. In this study, a complex of porous CaCO 3 and tannic acid-iron(III), named as PCC@TA(Fe III ), was fabricated and used as carrier for prometryn (PMT) to obtain a pH-controlled release herbicide of PCC/PMT@TA(Fe III ). Under neutral pH condition, the PMT release rate from PCC/PMT@TA(Fe III ) was merely 19 % while reached about 80 % at pH 5.5 and 8.5. Such pH controlled-release behavior of PMT was probably related to the pH-dependent structure transformation of PCC@TA(Fe III ). The release kinetic mechanism was in conformity with the parabolic diffusion model. Pot experiment result indicated that PCC/PMT@TA(Fe III ) showed a higher control efficacy against Setaria viridis compared with PMT alone. Additionally, PCC@TA(Fe III ) could effectively reduce the leaching loss of PMT in soil and show a good biosafety . Thus, this work provides a novel approach to improve control efficacy and relieve environmental pollution risks of pesticide.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Sitian Li,Yongtao Wang,Huaiqing Jiang,Yueyue Bai,Tao Chen,Min Chen,Mengze Ma,Shenyu Yang,Yan Wu,Chaochen Shi,Fazhan Wang,Yazhou Chen
CCL21, a secondary lymphoid tissue chemokine, plays an important role in generating an effective anti-tumor immune response. In this study, a genetically modified CCL21 was developed by inserting a pH low insertion peptide to establish a CCL21-rich microenvironment for tumors. The fusion tag thioredoxin (Trx) was designed and fused at the N-terminal of the recombinant protein to protect it from being irrevocably misfolded in microbial host cells. The prokaryotic expression vector pET32a-CCL21-pHLIP was constructed and successfully expressed in E. coli BL21 (DE3) with a soluble expression form and a molecular weight of ~35 kDa. The induction conditions were optimized to obtain an extremely high yield of 6.7 mg target protein from 31.1 mg total protein. The 6xHis tagged Trx-CCL21-pHLIP was purified using Ni-NTA resin, and it was confirmed using SDS-PAGE and Western blot analyses. Consequently, the Trx-CCL21-pHLIP protein was successfully displayed on the cancer cell surface in a weak acidic microenvironment and showed the same ability as CCL21 in recruiting CCR7-positive cells. Additionally, the CCL21 fusion protein with or without Trx tag showed similar functions. Therefore, the study implies the feasibility of directing a modular genetic method for the development of protein-based drugs.
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Pharmaceutics
·
2023
·Vol. 15
·期 2
·668
·
IF 5.4
Jie Zhu,Rui Gao,Zhongshi Wang,Zhiming Cheng,Zhonghua Xu,Zaiyang Liu,Yiqun Wu,Min Wang,Yuan Zhang
While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted drug delivery system to control drug release and alleviate side effects. In this study, a pH-responsive nonapeptide hydrogel was designed and fabricated for the tumor-targeted drug delivery of doxorubicin (DOX). Using a solid-phase synthesis method, a nonapeptide named P1 peptide that is structurally akin to surfactant-like peptides (SLPs) due to its hydrophobic tail and hydrophilic head was synthesized. The physicochemical properties of the P1 hydrogel were characterized via encapsulation capacity, transmission electron microscopy (TEM), circular dichroism (CD), zeta potential, rheological analysis, and drug release studies. We also used in vitro and in vivo experiments to investigate the cytocompatibility and tumor inhibitory efficacy of the drug-loaded peptide hydrogel. The P1 peptide could self-assemble into biodegradable hydrogels under neutral conditions, and the prepared drug-loaded hydrogels exhibited good injectability and biocompatibility. The in vitro drug release studies showed that DOX-P1 hydrogels had high sensitivity to acidic conditions (pH 5.8 versus 7.4, up to 3.6-fold). Furthermore, the in vivo experiments demonstrated that the DOX-P1 hydrogel could not only amplify the therapeutic effect but also increase DOX accumulation at the tumor site. Our study proposes a promising approach to designing a pH-responsive hydrogel with controlled doxorubicin-release action based on self-assembled nonapeptides for targeted chemotherapy.Keywords:peptide hydrogel;pH responsive;tumor targeted;drug delivery;doxorubicin;osteosarcoma
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Feng Wang,Chao Li,Haohao Wang,Lu Yu,Fuming Zhang,Robert J. Linhardt
Natural amino acid polymers have been wide-used as bio-compatible emulsion stabilizers . In this study, Amphiphilic O(Phe- r -Glu)s were synthesized through the papain-catalyzed random polymerization of L -phenylalanine and L -glutamate with the major degree of polymerization value of 6–7. The polymerization yield was increased by more than 35 % using choline to reduce the energy barrier for the amino substrates to form the tetrahedral intermediate with the catalytic triad. The squalene/water emulsions stabilized by O(Phe- r -Glu) nanoparticles were pH-insensitive at pH 1–12. The investigation of mechanism found the combined effects of steric hindrance , electrostatic repulsion and the viscosity of the emulsion contributed to the stability of the emulsion droplets. Under acidic condition, the layers of O(Pho- r -Glu)s particle aggregates formed around the emulsion droplets and the higher viscosity of emulsion mainly contributed to the stability of emulsions . At basic condition, the strong electrostatic repulsion between emulsion droplets covered by the negatively charged O(Pho- r -Glu) particles and the steric hindrance contributed mainly to the prevention of the coalescence of emulsion droplets. The application of enzymatically synthesized amphiphilic peptides in emulsion, along with tunable performance through the polymerization of amino substrates, is in line with the sustainable development requirements in fields such as pharmaceuticals, food and cosmetics.
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MATERIALS & DESIGN
·
2022
·
IF 9.417
Hong Ding,Xiang Zhang,Zheng Liu,Juehan Wang,Ce Zhu,Qian Chen,Yong Huang,Youwei Ai,Ruibang Wu,Ganjun Feng,Li Zhang,Limin Liu
Lower back pain is a significant contributor to disability and incapacity in adults. Up to 40 % of lower back pain is considered to be caused primarily by disc degeneration. The pH value in the intervertebral disc (IVD) usually decreases with the progression of degeneration, which can act as an initiator to trigger the release of drugs precisely for inhibiting the intervertebral disc degeneration (IDD). Herein, we fabricated a pH-responsive metal organic framework (MOF) to load anti-inflammatory protocatechuic acid (PCA), followed by the encapsulation of hyaluronic acid (HA), the final product was abbreviated as [email protected] The results showed that the acidic microenvironment could trigger drug release from [email protected] featured by an increasing release proportion with pH decreasing. The cell assessment indicated that [email protected] could suppress the inflammatory response of the nucleus pulposus significantly, downregulate the expression of related inflammatory markers (IL-6, ROS, NLRP-3 etc.) and promote the expression of nucleus pulposus specific markers. The administration of [email protected] in rat disc degeneration model was proven able to effectively delay the degeneration process. The pH-sensitive [email protected] may offer an effective strategy to precisely treat the IDD with desired therapeutic effects.
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BIOMATERIALS
·
2022
·
IF 15.304
Xuedi Zhang,Xue Zhao,Zheng Hua,Shanghua Xing,Jiaxuan Li,Siyuan Fei,Mingqian Tan
Smart delivery systems with stimuli-responsive capability are able to improve the bioaccessibility through increasing the solubility, physicochemical stability and biocompatibility of bioactive compounds. In this study, the astaxanthin nanoparticles with reactive oxygen species (ROS) and pH dual-response function were design and constructed using poly (propylene sulfide) covalently modified sodium alginate as carriers based on ultrasonic assisted self-assembly strategy. Atomic force microscope and scanning electron microscope analysis showed that the nanoparticles were spherical in shape with a size of around 260 nm. Meanwhile, the astaxanthin nanoparticles showed both pH and ROS stimuli-responsive release characteristics. In vitro cell experiments showed that astaxanthin nanoparticles significantly inhibited the production of ROS and mitochondrial depolarization induced by oxidative stress . In vivo colitis experiment of mice revealed that astaxanthin nanoparticles could significantly relieve colitis, protect the integrity of colon tissue and restore the expression of tight junction proteins ZO-1 and occludin . The abundance of Lactobacillus and Lachnospiraceae , and the ratio of Firmicutes/Bacteroidota of gut microbiota were significantly improved after intervention of the stimuli-responsive astaxanthin nanoparticles. This work provided a simple strategy for constructing ROS/pH dual response delivery system, which provided an experimental basis for improving the oral bioavailability of hydrophobic active compounds.
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JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2023
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IF 8.7
Yangxiaoxiao Shi,Yunjiang Yu,Mingdeng Xiang,Peixin Cui,Jiaqi Cui,Feng Zhang,Jun Jiang,Renkou Xu
Investigation of the inherent relationship between soil physicochemical properties and pollutant's bioaccessibility (BAc) by analyzing different soil types may produce erroneous results or bias, owing to the complexity of natural soil characteristics. However, use of single factor analysis (e.g., soil pH, organic matter) facilitates evaluation of the transition. In this study, the inherent relationship between soil properties and the BAc of molybdenum (Mo) was evaluated in two typical variable-charge soils (Ferralosol and Ferrosol) and constant-charge soils (Alfisol and Inceptisol) spiked with Mo after adjusting their pH and organic carbon content. The Unified Bioaccessibility Research Group of Europe (BARGE) Method (UBM) was applied to evaluate the BAc of Mo in the gastric and intestinal phase (GP and IP, respectively). Isothermal adsorption experiment, Tessier sequential extraction, and field emission scanning electron microscope-energy dispersive spectroscopy (FESEM-EDS) analysis were conducted on these spiked soils. The results indicated that the BAc of Mo in IP (27.42–80.41%) was significantly higher than that in GP (2.52–28.53%). A significantly lower level of BAc of Mo was found in the variable-charge soils, when compared with that in the constant-charge soils. Furthermore, significant negative correlations were identified between the BAc and adsorption of Mo, which decreased with soil pH. These negative correlations can be attributed to the increase in soil negative charge density and enhancement of Mo desorption by hydroxyl, which reinforce the repulsion between Mo and soil particles with increasing soil pH; this was further confirmed by the decrease in Mo adsorption with Alfisol pH. The Mo fractions and FESEM-EDS patterns confirmed that the BAc of Mo in GP was negatively correlated with soil organic carbon (SOC) content, possibly owing to an increase in Mo retention by SOC. These findings indicated that the health risk of Mo contamination in low pH and SOC-rich variable-charge soil is relatively low, thus providing references for rationalizing risk assessment and remediating Mo-polluted soil.
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