ACS Applied Nano Materials
·
2025
·
IF 5.5
Hui Qiao,Wenxia Zhang,Dongmei Zhang,Wenjun Yan,Jianguo Li,Yingqi Li
The redox homeostasis in tumor cells is an innate defense barrier for reactive oxygen species (ROS)-mediated tumor therapy. Herein, an intratumoral cascade-responsive multifunctional nanodiamond-based platform (NPCD) with a hydrodynamic diameter of 191 ± 5 nm triggering redox dyshomeostasis is fabricated by Cu2+-mediated coordination for polylysinated nanodiamond and doxorubicin (DOX) to achieve cancer-specific diagnosis and therapy. The NPCD nanoplatform enables precise tumor fluorescence localization and chemotherapy through a “turn on” effect due to being specifically activated by GSH to trigger DOX release at a low-pH tumor-specific environment instead of normal cells. Furthermore, NPCD realizes Cu+-based chemodynamic therapy (CDT) and induces GSH depletion by Cu2+ reduction to support CDT. These cause intracellular redox dyshomeostasis, making tumor cells more sensitive to the NPCD nanoparticles. Additionally, NPCD also possesses the intrinsic ability to reverse drug resistance. Of note, NPCD mainly accumulates in the tumor site in 4T1 tumor-bearing mice and enhances the efficacy of therapeutic interventions with negligible side effects. More interestingly, combined with programmed cell death ligand 1 antibody (anti-PD-L1) and imiquimod (R837), NPCD significantly suppresses distant tumor growth, indicating a good immune response. Therefore, this work opens perspectives for the further development of synergistic therapy through a Cu2+-mediated intratumoral cascade reaction.
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Dongjing Cai,Xia Xu,Weiqian Zeng,Zheng Wang,Cheng Chen,Yunan Mo,Piyanat Meekrathok,Dandan Wang,Pengwei Peng,Zhigang Peng,Jian Qiu
Cellular senescence is a natural barrier of the transition from premalignant cells to invasive cancer. Pharmacological induction of senescence has been proposed as a possible anticancer strategy. In this study, we found that deoxyarbutin inhibited the growth of glioblastoma (GBM) cells by inducing cellular senescence, independent of tyrosinase expression. Instead, deoxyarbutin induced mitochondrial oxidative stress and damage. These aberrant mitochondria were key to the p53-dependent senescence of GBM cells. Facilitating autophagy or mitigating mitochondrial oxidative stress both suppressed p53 expression and alleviated cellular senescence induced by deoxyarbutin. Thus, our study reveals that deoxyarbutin induces mitochondrial oxidative stress to trigger the p53-dependent senescence of GBM cells. Importantly, deoxyarbutin treatment resulted in accumulation of p53, induction of cellular senescence, and inhibition of tumor growth in a subcutaneous tumor model of mouse. In conclusion, our study reveals that deoxyarbutin has therapeutic potential for GBM by inducing mitochondrial oxidative stress for p53-dependent senescence of GBM cells.
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Jingyuan Wang,Ronggang Zhai,Yifan Ma,Haoyu Chen,Danyang Jing,Huaiyu Yang,Yi Wang
Owing to their small size, morphology and release modification properties, nanopesticides are considered promising alternative strategies for enhancing biological activity and minimizing pesticide losses. In this study, we used a colloidal self-assembly method to develop a morphology-stable, regularly rod-shaped nanoselenium pesticide carrier (NSer), which was further modified with chitosan. After loading penthiopyrad (PEN), the biological activity of NSer@PEN and its impact on the physiological and biochemical processes of plants were further compared with those of spherical nanoselenium pesticides (NSes@PEN) and commercial materials (20 % PEN SC). The biological activities were quantified through the EC 50 values, which revealed that NSer@PEN (0.71 mg/L) and NSes@PEN (1.09 mg/L) exhibited significantly greater activity against Colletotrichum orbiculare Arx compared to 20 % PEN SC (2.70 mg/L). Moreover, through further investigation into the impact of nanopesticides on plant root exudates, Fourier transform infrared spectroscopy (FTIR) and two-dimensional correlation spectroscopy (2D-COS) analysis revealed that the ketone C O bond exhibited the strongest binding affinity, and the C O bond of phenols contributed significantly to the binding of cucumber root exudates induced by NSer@PEN, resulting in a mild response of the plant. The morphology-dependent nanoselenium carriers developed in this work are expected to enhance biological activity and reduce plant stress caused by pesticides, tackling one of the application challenges of pesticides.
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高影响因子
Discover Nano
·
2024
·Vol. 19
·期 1
·1-16
·
IF 0
Sun Yunhao,Ying Kaijun,Sun Jian,Qiu Limin,Wang Yao,Ji Mingming,Zhou Lulu,Chen Jinjin
Cisplatin (CDDP) is the primary drug used in the initial treatment of esophageal cancer (EC). However, its side effects and resistance can limit its effectiveness in clinical therapy. Curcumin (Cur)-mediated glutathione (GSH) depletion can reverse resistance, enhance the chemosensitivity of CDDP, and further improve the efficacy of platinum-containing chemotherapy in the treatment of esophageal cancer. However, it is also faced with problems of poor water solubility and low bioavailability in vivo, which severely hinders cancer treatments. In order to address these issues, we developed a novel nanotherapeutic system called CDCZA, combining Cur/CDDP/Cu/ZIF8@Au to enhance chemotherapy through GSH depletion and chemodynamic therapy through self-produced H 2 O 2 . Cu and CDDP were precisely co-loaded into Cu/ZIF8 nanoparticles using a one-pot method, then ultra-small gold nanoparticles mimicking glucose oxidase (Au nanoparticles) were embedded in the outer shell to create the CDCZA nano system. The released Cur could notably decrease intracellular GSH content and thus improve the chemosensitivity of CDDP, resulting in severe cellular apoptosis. And the Au nanoparticles effectively enabled chemodynamic therapy enhancement by accelerating the depletion of β-D-glucose into H 2 O 2 . As a result, the CDCZA nanoparticles showed increased tumor accumulation and improved antitumor effectiveness in a model of EC. Taken together, this work provides a new idea for the clinical design of efficient treatment reagents for EC.
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Materials Today Bio
·
2025
·
IF 10.2
Zhenying Diao,Youcheng Liang,Yong Liu,Dou Zhang,Long Qiu,Jianbo Sun,Qiaoyou Lu,Yanlei Liu,Daxiang Cui,Ting Yin
Blockade of heat shock protein 90 (HSP90) expression in multimodal synergistic therapy has a great prospect for cancer treatment. Nanomaterials combined with bioinformatic analysis provides accurate guidance for the design of anti-HSP90 nanomedicines. Herein, a NIR-II-responsive nanoplatform was developed under bioinformatics guided to effectly inhibit HSP90 for enhanced synergistic mild-photothermal chemotherapy without any notable tissue damage. The nanoplatforms were assembled from NIR-II-responsive gold nanobipyramids (GNBs) combined with curcumin (Cur) via hydrophobic-hydrophobic interactions and hydrogen bonds. On the basis of drug discovery and network pharmacology, we found that Cur has impressive anti-HSP90 capability and analyzed its therapeutic mechanism against NSCLC. Under the irradiation of NIR-II light, the obtained GNBs-Cur blocked the expression of HPS90 and inhibited related antiapoptotic pathways, thus enhancing the mild PTT of GNBs under 1064 nm laser irradiation. Meanwhile, Cur served as chemotherapeutic agents to induce apoptosis in tumor cells. In vivo photoacoustic imaging-guided, GNBs-Cur achieved effective tumor elimination through mild-photothermal chemotherapy without systemic toxicity. Overall, this work provides a new therapeutic modality paradigm for potential NSCLC treatment on the basis of synergistic therapies.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Wenjing Ren,Huiru Zhu,Dongshuai Shang,Xinyu Zhou,Hua Zhang,Juan Zhang,Guangpu Liu,Yunbo Wei,Kaiming Wang,Chengshi Jiang,Ping Sun
In this article, folic acid (FA) modified biodegradable poly (ethylene glycol) (PEG 2K ) was chosen as the polymeric skeleton to conjugate with curcumin (CUR) via a disulfide bond to construct a reduction-responsive drug delivery system (FA-PEG 2K -SS-CUR), aiming at improving the solubility of CUR and providing a targeted, efficient, and low side-effect anti-cancer nano-preparation. The polymers were synthesized through three steps to develop FA-PEG 2K -SS-CUR micelles, with a drug loading capacity of up to 10.9% and good stability. The particle of FA-PEG 2K -SS-CUR micelles determined by Malvern Mastersizer was 79.14±2.2 nm, and a hemolysis assay confirmed their good biocompatibility. The reduction sensitivity of FA-PEG 2K -SS-CUR micelles was verified by adding dithiothreitol (DTT) to the release medium, showing a programmed drug release mode with 60.41% released within 72 h, indicating a certain sustained-release capability. In vitro cytotoxicity assays showed that the FA-PEG 2K -SS-CUR micelles were more cytotoxic than free CUR. Additionally, FA-PEG 2K -SS-CUR micelles exhibited a higher cellular uptake rate than micelles without FA. Hence, the prepared multifunctional FA-PEG 2K -SS-CUR micelles is a promising anti-tumor nano-preparation.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaohong Zhu,Tiantian Feng,Yidan Chen,Yao Xiao,Wei Wen,Xiuhua Zhang,Dong Wang,Shengfu Wang,Jichao Liang,Huayu Xiong
Skin wound healing, particularly diabetic wound healing, is a common clinical challenge. Reducing bacterial infection and promoting angiogenesis are key strategies for diabetic wound healing. In this study, we construct the porphyrin-based Cu-covalent organic frameworks (Cu-COF) through a Schiff base condensation reaction, and then functionalize Cu-COF with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-DSPE), denoted as PEG/Cu-COF, for enhancing diabetic wound healing. PEG/Cu-COF exhibits dual enzymatic properties (glutathione (GSH) oxidase-like and peroxidase (POD)-like nanozymes), facilitating the depletion of GSH and the generation of reactive oxygen species (ROS) through a self-cascading enzymatic reaction, thereby leading to chemodynamic therapy (CDT). Density functional theory (DFT) calculations are employed to investigate the catalytic mechanism and the results reveal that Cu-COF exhibits higher catalytic activity for POD. Moreover, porphyrin-based COF generates singlet oxygen and localize heating under white light and near-infrared irradiation, respectively. Both in vitro and in vivo experiments demonstrate that PEG/Cu-COF exhibits multimodal synergistic sterilization and promotes angiogenesis, collagen deposition, and re-epithelialization during diabetic wound healing. This work highlights the potential utilization of PEG/Cu-COF for self-supplying hydrogen peroxide (H 2 O 2 ) and amplifying self-cascade reactions to address the limitations of enzymatic treatment, while the synergistic effect of phototherapy improves sterilization and minimizes side effects in vivo .
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FASEB JOURNAL
·
2024
·Vol. 38
·期 4
·e23470
·
IF 4.4
Guangyu Zhou,Pai Liu,Chen Zhang,Qun Huang,Zixia Zhao,Si Wu,Detian Li,Hongbo Liu
Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with β-glycerophosphate (β-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and β-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that β-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in β-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Hongwei Li,Le Kang,Shirong Dou,Yiming Zhang,Yumei Zhang,Ning Li,Yangang Cao,Mengyun Liu,Deen Han,Kai Li,Weisheng Feng
Background Gleditsiae Sinensis Fructus (GSF) is commonly used in traditional medicine to treat respiratory diseases such as bronchial asthma. However, there is a lack of research on the chemical composition of GSF and the pharmacological substance and mechanism of action for GSF in treating bronchial asthma. Purpose The chemical constituents of GSF were analyzed using ultrahigh-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). In this study, we combined network pharmacology, molecular docking techniques, and experimental validation to explore the therapeutic efficacy and underlying mechanism of GSF in the treatment of bronchial asthma. Methods Characterization of the chemical constituents of GSF was conducted using UHPLC-Q-Orbitrap HRMS. The identified chemical components were subjected to screening for active ingredients in the Swiss Absorption, Distribution, Metabolism, and Excretion (ADME) database. Relevant databases were utilized to retrieve target proteins for the active ingredients and targets associated with bronchial asthma disease, and the common targets between the two were selected. Subsequently, the protein-protein interaction (PPI) network was constructed using the String database and Cytoscape software to identify key targets. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Metascape database. The "component-common target" network was constructed using Cytoscape to identify the primary active ingredients. Molecular docking validation was conducted using AutoDock software. The bronchial asthma mouse model was established using ovalbumin (OVA), and the lung organ index of the mice was measured. Lung tissue pathological changes were observed using hematoxylin and eosin (HE), Periodic Acid-Schiff (PAS), and Masson staining. The respiratory resistance (Penh) of the mice was assessed using a pulmonary function test instrument. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IgE, IL-4, IL-5, and IL-13 in the mouse serum. Immunofluorescence staining was performed to detect the protein expression levels of AKT and PI3K in the lung tissues. An in vitro experiment was performed to observe the effects of echinocystic acid (EA) on IL-4 stimulated Human ASMCs (hASMCs). Cell viability was measured using a CCK-8 assay to calculate the IC50 value of the EA. A wound healing test was conducted to observe the effect of EA on degree of healing. RT-qPCR was performed to detect the influence of EA on the mRNA expression levels of ALB, SRC, TNF-α, AKT1, and IL6 in the cells. Results A total of 95 chemical constituents were identified from the GSF. Of these, 37 were identified as active ingredients. There were 169 overlapping targets between the active ingredients and the disease targets. A topological analysis of the protein-protein interaction (PPI) network identified the core targets as IL6, TNF, ALB, AKT1, and SRC. An enrichment analysis revealed that the treatment of bronchial asthma with GSF primarily involved the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway, among others. The primary active ingredients included 13(s)-HOTRE, linolenic acid, and acacetin. The molecular docking results demonstrated a favorable binding activity between the critical components of GSF and the core targets. Animal experimental studies indicated that GSF effectively improved symptoms, lung function, and lung tissue pathological changes in the OVA-induced asthmatic mice, while alleviating inflammatory responses. GSF decreased the fluorescent intensity of the AKT and PI3K proteins. The IC50 value of EA was 30.02μg/ml. EA (30) significantly promoted the proliferation of IL4-stimulated hASMCs cells. EA (30) significantly increased the expression of ALB and SRC mRNA and decreased the expressions of TNF-α, AKT, and IL6 mRNA. Conclusion The multiple active ingredients found in GSF exerted their anti-inflammatory effects through multiple targets and pathways. This preliminary study revealed the core target and the mechanism of action underlying its treatment of bronchial asthma. These findings provided valuable insights for further research on the pharmacological substances and quality control of GSF.
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高影响因子
SENSORS
·
2024
·Vol. 24
·期 20
·6701
·
IF 3.4
Zhao-Jiang Yu,Ting-Ting Yang,Gang Liu,De-Hua Deng,Lin Liu
This work reported gold nanoparticles (AuNPs)-based colorimetric immunoassay with the Cu-based metal–organic framework (MOF) to load pyrroloquinoline quinone (PQQ) for the catalytic oxidation of cysteine. In this method, both Cu2+and PQQ in the MOF could promote the oxidation of inducer cysteine by redox cycling, thus limiting the cysteine-induced aggregation of AuNPs and achieving dual signal amplification. Specifically, the recombinant carcinoembryonic antigen (CEA) targets were anchored on the MOF through the metal coordination interactions between the hexahistidine (His6) tag in CEA and the unsaturated Cu2+sites in MOF. The CEA/PQQ-loaded MOF could be captured by the antibody-coated ELISA plate to catalyze the oxidation of cysteine. However, once the target CEA in the samples bound to the antibody immobilized on the plate surface, the attachment of CEA/PQQ-loaded MOF would be limited. Cysteine remaining in the solution would trigger the aggregation of AuNPs and cause a color change from red to blue. The target concentration was positively related to the aggregation and color change of AuNPs. The signal-on competitive plasmonic immunoassay exhibited a low detection limit with a linear range of 0.01–1 ng/mL. Note that most of the proteins in commercial ELISA kits are recombinant with a His6tag in the N- or C-terminal, so the work could provide a sensitive plasmonic platform for the detection of biomarkers.
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高影响因子
Frontiers in Nutrition
·
2024
·
IF 4
Wei Shulin,Li Mingxing,Zhao Long,Wang Tiangang,Wu Ke,Yang Jiayue,Tang Mingyun,Zhao Yueshui,Shen Jing,Du Fukuan,Chen Yu,Deng Shuai,Xiao Zhangang,Wei Mei,Li Zhi,Wu Xu
Introduction: Liuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP.Methods: LGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated.Results: The results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity.Discussion: The results of present study would be of help to gain the understanding of structure–activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.
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高影响因子
DYES AND PIGMENTS
·
2025
·
IF 4.2
Jing Zhu,Songfang zhao,Ruifang Guan,Hao Zhang
Heteroatom doping can achieve specific regulation of carbon dots by changing their nanostructure, electronic structure and band gap. Here, we synthesized nitrogen-sulfur co-doped carbon dots (N, S-CDs) with full-spectrum fluorescence emission capability. Through comprehensive structural analysis using XPS, FTIR, and other characterization techniques, it was revealed that most of the nitrogen atoms were integrated into the carbon core of the N, S-CDs. Meanwhile, sulfur atoms were identified on the surface of the N, S-CDs, incorporated as functional groups. This unique structural configuration provides a foundation for understanding the solvent effect on N, S-CDs. Specifically, as the polarity of the solvent increases, the fluorescence emission of the N, S-CDs experiences a red-shift. The varying hydrogen donor abilities of different solvents contribute to changes in fluorescence emission. Notably, N, S-CDs exhibit near-infrared fluorescence emission when dissolved in acetic acid solvent. Under the synergistic effect of solvent polarity and hydrogen bonding, the fluorescence emission of N, S-CDs achieves full-spectrum luminescence, spanning from blue light to near-infrared. It is particularly interesting to observe that when N, S-CDs are dispersed in polyvinyl alcohol (PVA) films by dissolving them in three different solvents, the red, green, and yellow light emission can be achieved. When coated onto Light Emitting Diode (LED) lamp beads, these films exhibit versatile light emission properties. This provides inspiration for the development and preparation of LED fluorescent materials. Meanwhile, thanks to the excellent luminescent properties of N, S-CDs in water, they can be used for targeted localization of lysosomes in biological cells.
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危险品化学品经营许可证（带存储）