OncoTargets and Therapy
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2022
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IF 4.345
Songjiang Wu,Yanying Yang,Feiping Li,Lifu Huang,Zihua Han,Guanfu Wang,Hongyuan Yu,Haiping Li
Introduction Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time.Methods In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis.Results Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE.Conclusion Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer.
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高影响因子
Journal of Materials Chemistry B
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2022
·Vol. 10
·期 42
·8664-8671
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IF 7.571
Han Yang,Xiang Gu,Yan Li,Ke Zhang,Xihong Liu,Chengyao Huang,Yu Ren,Chao Qi,Kaiyong Cai
Bacterial wound infection has brought a serious threat to human health and caused huge economic losses. Attempts to develop biomaterials with excellent antibacterial effects are meaningful to promote wound healing. Herein, we report a multifunctional nanoreactor with nutrient consumption and reactive oxygen species (ROS) generation capabilities for antibacterial and skin wound repair. The nanoreactor was constructed by the encapsulation of glucose oxidase (GOx) into a Cu2+-doped zeolite-based imidazole framework (ZIF-8) through a one-pot synthesis method. The nanoreactor not only consumes the nutrients of bacteria by the GOx-driven oxidation reaction, but also generates highly toxic hydroxyl radicals (˙OH) to kill bacteria via a Cu+-mediated Fenton-like reaction. Moreover, Zn2+ released from the nanoreactor is also capable of exhibiting synergistic antibacterial activity. In addition to mediating Fenton-like reactions, Cu2+ promotes angiogenesis to accelerate wound healing. Thus, the multifunctional nanoreactor has the ability to cut off the nutrient supply and starve the bacteria, produce ROS to kill bacteria, and promote angiogenesis to accelerate wound healing, enabling it to be promising for the treatment of wound infection.
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International Journal of Nanomedicine
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2022
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IF 7.033
Chunyan Shao,Ziwei Yu,Tongwang Luo,Bin Zhou,Quanjiang Song,Zhuoyue Li,Xiaoqiang Yu,Sheng Jiang,Yingshan Zhou,Wanyu Dong,Xingdong Zhou,Xiaodu Wang,Houhui Song
Introduction Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication. Methods In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H 2 O 2 ) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID 50 , and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot. Results The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H 2 O 2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi. Conclusion These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.
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Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 21
·4083-4095
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IF 7.571
Yajie Pu,Penghui Wang,Rong Yang,Xiaoyan Tan,Tianqi Shi,Juping Ma,Wenliang Xue,Bo Chi
Chronic wounds, especially diabetic wounds, involve abnormally long inflammatory periods due to their pathological microenvironment of high reactive oxygen species (ROS) levels and lack of blood vessels. Here, via a mild, simple and feasible fabrication approach, a sustained oxygenation system is proposed, consisting of MnO2 nanosheets and a dual-network hydrogel fabricated from natural biomaterials including silk fibroin (SF) and carboxymethyl cellulose (CMC). Compared with the initial value (61.09 kPa), the compression modulus of the dual-network hydrogel increased by 116.2% through the coordination of strong covalent bonds and sacrificial coordination bonds constructed by enzymatic crosslinking and UV-irradiation crosslinking; the intrinsic shear-thinning effect endows the dual-network hydrogel with satisfactory injectable properties to be customized as a predetermined shape to accommodate the irregular wounds of diabetes. The encapsulated MnO2 nanosheets can catalyze the excessive ROS into necessary O2in situ and, after co-incubating with the SF/CMC@MnO2 hydrogels, cells in oxidative stress show significantly lower ROS (3 times) and higher O2 (17 times) levels that are conductive to relieving oxidative stress, promoting angiogenesis and reducing inflammation in vivo. Meanwhile, these SF-based hydrogels can offset the overexpression of matrix metalloproteinases (MMPs) in diabetic wounds (more than 80%) and promote remodeling of the extracellular matrix. Eventually, wound healing rates >76% in 7 days and 100% in 14 days were achieved by the bio-fabricated nanocomposite hydrogel and are remarkably faster than the commercial dressing healing rates (<30% in 7 days and <80% in 14 days). These results indicate that this bio-fabricated hydrogel system with multiple and customizable functions has great promise in the personalized clinical care of chronic wounds.
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International Journal of Nanomedicine
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2023
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IF 8
Jing Wang,Weijian Chen,Wenxiang Du,Hongjie Zhang,Matthias Ilmer,Lei Song,Yuan Hu,Xiaopeng Ma
Introduction Tamoxifen (TAM) has proven to be a therapeutic breakthrough to reduce mortality and recurrence in estrogen receptor-positive (ER+) breast cancer patients. However, the application of TAM exhibits low bioavailability, off-target toxicity, instinct and acquired TAM resistance.Methods We utilized black phosphorus (BP) as a drug carrier and sonosensitizer, integrated with TAM and tumor-targeting ligand folic acid (FA) to construct TAM@BP-FA for synergistic endocrine and sonodynamic therapy (SDT) of breast cancer. The exfoliated BP nanosheets were modified through in situ polymerization of dopamine, followed by electrostatic adsorption of TAM and FA. The anticancer effect of TAM@BP-FA was evaluated through in vitro cytotoxicity and in vivo antitumor model. RNA-sequencing (RNA-seq), quantitative real-time PCR, Western blot analysis, flow cytometry analysis and peripheral blood mononuclear cells (PBMCs) analysis were performed for mechanism investigation.Results TAM@BP-FA had satisfactory drug loading capacity, the TAM release behavior can be controlled through pH microenvironment and ultrasonic stimulation. An amount of hydroxyl radical (∙OH) and singlet oxygen (1O2) were as expected generated under ultrasound stimulation. TAM@BP-FA nanoplatform showed excellent internalization in both TAM-sensitive MCF7 and TAM-resistant (TMR) cells. Using TMR cells, TAM@BP-FA displayed significantly enhanced antitumor ability in comparison with TAM (7.7% vs 69.6% viability at 5μg/mL), the additional SDT further caused 15% more cell death. RNA-seq unraveled the TAM@BP-FA antitumor mechanisms including effects on cell cycle, apoptosis and cell proliferation. Further analysis showed additional SDT successfully triggering reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) reduction. Moreover, PBMCs exposed to TAM@BP-FA induced an antitumor immune response by natural killer (NK) cell upregulation and immunosuppression macrophage reduction.Conclusion The novel BP-based strategy not only delivers TAM specifically to tumor cells but also exhibits satisfactory antitumor effects through targeted therapy, SDT, and immune cell modulation. The nanoplatform may provide a superior synergistic strategy for breast cancer therapy.
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JOURNAL OF HYDROLOGY
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2023
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IF 6.4
Yanting Zhang,Na Zhang,Chenglong Yu,Hui Liu,Songhu Yuan
Production of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (•OH), has been increasingly discovered upon oxygenation of reduced species in anoxic soil and sediment pore waters. We therefore hypothesize that H 2 O 2 and •OH can be produced during groundwater abstraction and discharging due to oxygenation. To evaluate the capacities of H 2 O 2 and •OH accumulation during groundwater oxygenation, here we measured H 2 O 2 and •OH accumulations during dark oxygenation of groundwater abstracted from different depths of 11 wells adjacent to the Han River. This abstraction could simulate the scenarios of groundwater abstraction by riverside pumping and also of groundwater discharging in hyporheic zones. Results showed that H 2 O 2 and •OH formed during oxygenation of the groundwater with low Eh values (< 63 mV), and only H 2 O 2 (< 3.37 μM) formed for the groundwater with high Eh values (63–206.5 mV). Statistical analysis indicated that dissolved Fe(II) was mainly accountable for the production of measurable •OH in the low Eh locations. The aquifer conditions (i.e., aquifer lithology) and external environmental factors (i.e. pumping disturbance) within short-term abstraction process had negligible influence on ROS production. The relationship between ROS production and groundwater chemistry was further explored by multiple linear regression, which deduced the quantitative models for estimating ROS production upon oxygenation of groundwater from different sources with different chemistry. Using the abstracted groundwater in western Bengal basin as an example, the estimated results indicated that ROS production had a great potential to oxidize the typical contaminant of As(III). As ROS, particularly •OH, represents strong oxidants, our findings implicate an overlooked oxidative capacity during groundwater abstraction and discharging in hyporheic zones or other areas, which could lead to the oxidative transformation of substances and the oxidative stress of microbial metabolism and associated biogeochemical processes in the environments suffering from groundwater oxygenation. This oxidative capacity is particularly important when the groundwater with low Eh values, i.e., under strongly reductive conditions, were abstracted and oxygenated in the surface.
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JOURNAL OF CONTROLLED RELEASE
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2021
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IF 9.776
Ye Wu,Yu Wang,Linyu Long,Cheng Hu,Qingquan Kong,Yunbing Wang
Fabricating injectable hydrogel with multifunctions that matchs the highly ordered healing process of skin regeneration has greatly desired in treatment of chronic diabetic wounds. Herein, a pH/reactive oxygen species (ROS) dual responsive injectable glycopeptide hydrogel based on phenylboronic acid-grafted oxidized dextran and caffeic acid-grafted ε-polylysine was constructed, which exhibited inherent antibacterial and antioxidant capacities . The mangiferin (MF) with the ability to promote angiogenesis was encapsulated into pH-responsive micelles (MIC). Subsequently, diclofenac sodium (DS) with anti-inflammatory activities and MIC@MF were embedded into the hydrogel. The hydrogel possessed good biodegradability, stable rheological property and self-healing ability, and could realize the spatiotemporal delivery of DS and MF. The in vitro and in vivo data showed that the hydrogel was biocompatible with effective anti-infection, anti-oxidation and anti-inflammation at early stages, then further promoted angiogenesis and accelerated wound repairing. Collectively, this novel glycopeptide hydrogel provides a facile and effective strategy for chronic diabetic wound repairing.
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DRUG DELIVERY
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2021
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IF 6.419
Bingfeng Liang,Dangxia Zhou
Although podophyllotoxin (POD) demonstrates high efficiency to inhibit various cancers, its clinic application is limited to poor bioavailability. Nanoparticles derived from homodimeric prodrugs with high drug loading potential are emerging as promising nanomedicines. However, complete intracellular drug release remains a major hindrance to the use of homodimeric prodrugs-based nanomedicine. We sought to develop a reactive oxygen species (ROS) responsive POD dimeric prodrug by incorporating vitamin K3 (VK3) and Pluronic F127 to synthesize a spheroid nanoparticle (PTV-NPs). PTV-NPs with high POD content could release drugs under the ROS enrichment microenvironment in cancer cells. The released VK3 could produce abundant ROS selectively in tumor cells catalyzed by the overexpressed NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme. In turn, the resultant high ROS concentration promoted the conversion of POD dimeric prodrug to POD monomer, thereby achieving the selective killing of cancer cells with weak system toxicity. In vitro and in vivo studies consistently confirmed that PTV-NPs exhibit high drug loading potential and upstanding bioavailability. They are also effectively internalized by tumor cells, induce abundant intracellular ROS generation, and have high tumor-specific cytotoxicity. This ROS-responsive dimeric prodrug nanoplatform characterized by selective self-amplification drug release may hold promise in the field of antitumor drug delivery.
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Inorganics
·
2023
·Vol. 11
·期 11
·429
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IF 2.9
Li Liu,Siyu Li,Detai Shi,Qifu Bao,Tiangui Zhao,Wei Zhu,Xiaolong Li,Jianer Zhou
The emergence of drug resistance due to the overuse of antibiotics has made the prevention and treatment of invasive fungal infections caused byCandida albicans(C. albicans) a great challenge. Oxygen vacancy-rich inorganic materials show great promise in the antimicrobial field due to their unique physicochemical properties. Defect engineering can significantly optimize the electronic structure of inorganic materials to further enhance their antimicrobial activity. We designed oxygen vacancy defect-rich V6O13powders using the hydrothermal-calcination method and investigated their anti-C. albicansactivity. The results showed that the stronger antibacterial activity is attributed to the fact that the optimized V6O13powder oxygen vacancy defects induced a reduction reaction of dissolved oxygen in the environment, which produced ROS with strong oxidative properties, causing damage to the wall membrane ofC. albicansand leakage of intracellular material. The minimum inhibitory concentration (99% or more inhibition) of V6O13powders is 4 mg/mL. This work not only provides a facile method for constructing oxygen-rich vacancies in V6O13powders, but also provides new insights into the potential of inorganic materials optimized by defect engineering for efficient antimicrobial activity.
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Journal of Cleaner Production
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2023
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IF 11.1
Yaopeng Zhang,Miaojia Du,Hui Chen,Chensi Shen,Mengmeng Lou,Chenye Xu,Chunyan Ma,Fang Li
Adsorption enrichment coupled with oxidative degradation is a promising technique for eliminating tetracycline (TC) from an aqueous environment . However, the high cost associated with this technique limits its applicability. Thus, in this study, we synthesized Cu 2 O and CuFe 2 O 4 bimetallic-modified chitosan particles (Cu(I)–CuFe 2 O 4 @CS) with high adsorption efficiency and self-cleaning performance. The self-cleaning performance was driven by the in-situ generated reactive oxygen species (ROS). Batch experiments and characterization methods indicated that 97.39% of TC was rapidly adsorbed on the particles surface and subsequently degraded by in-situ generated ROS, to achieve a self-cleaning process. The Cu(I)–CuFe 2 O 4 @CS/TC system exhibited maximum O 2 • - and H 2 O 2 concentration of 12.95 μmol/L and 42.05 μmol/L, respectively. Cu 2 O was the main source of the ROS generation, while CuFe 2 O 4 effectively adsorbed TC and contributed to the synergistic accumulation of ROS. Moreover, the adsorbed TC with reductive functional properties facilitated the reduction of Fe(III)/Fe(II) and Cu(II)/Cu(I) cycles, thereby improving TC elimination efficiency.
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CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Lei Zhang,Minglu Hao,Liang Yao,Cheng Xing,Qingmei Wen,Zhining Zhang,Jingmou Yu,Jun Wang,Dongming Xing,Tao Zheng,P. Chen
Anthocyanins, a class of polyphenols possessing potent antioxidant properties, are limited in their applicability in biomedical industries owing to their low stability. This study harnessed the bioactive silk sericin to encapsulate anthocyanins and thereby conferred enhanced stability and multifunctional bioactivity. Meanwhile, experimental and computational methods were used to systematically probe the interaction between silk sericin and anthocyanins. The hydrogel formulation of silk sericin displayed higher encapsulation efficiency and concomitant improvements in stability under diverse conditions such as pH, metals, and temperature. Molecular simulations revealed that the amino acids, phenylalanine and tyrosine, with a hairpin structure were pivotal in the interaction between the two components, culminating in the formation of nanocomposites, a finding corroborated by the experimental results using various spectroscopic techniques. Significantly, the encapsulated anthocyanins exhibited enhanced bioactivity, particularly in their reactive oxygen species (ROS) scavenging ability. Leveraging the potent antioxidant properties of silk sericin and anthocyanins, the formulation evinced ROS-triggered wound healing functions by modulating factors such as TGF-β, IL-1β, TNF-α, IL-10, and VEGF. This study highlights the potential of utilizing two bioactive components derived from the same sericultural system to enhance stability and regulate bioactivity in tissue engineering applications.
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Nanoscale
·
2023
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IF 6.7
Yu Ran,Shanmei Yin,Pei Xie,Yaxue Liu,ying wang,Zongning Yin
Acute Lung Injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target to the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.
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