CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yipeng Pang,Maofang Zhao,Yuhan Xie,Yanping Wang,Yuxin You,Yongding Ke,Chaoyi Zhang,Xiaohan Chen,Yijia Yang,Chunlei Zhang,Xi Chen,Yi Liu,Xingtang Fang
The development of non-antibiotic strategies for combating bacterial infections, particularly through reactive oxygen species (ROS) accumulation accompanying inflammation, has attracted much attention. Despite Allicin (Ac) emerges as a promising antimicrobial agent with wide and remarkable bioactivity, it still displays quite limited ROS scavenging and anti-inflammation capacity due to uncontrolled and poor bioavailability. Herein, a multifunctional nanoplatform with pH-dependent and ROS-scavenging antibacterial, anti-inflammatory and proangiogenic properties is introduced to promote infected wound healing by integrating Ac into silver nanoparticles (AgNPs)-loaded zeolite imidazole framework (ZIF-8), namely Ac@ZIF-8/AgNPs. Primarily, the nanoplatform is activated and controlled release in the infection microenvironment, with disrupting biofilms, scavenging ROS and antibacterial capacitys, outperforming conventional Ac. Moreover, in the mouse models induced by bacterial infection, Ac@ZIF-8/AgNPs can alleviate the inflammatory condition, scavenge ROS, facilitate the regeneration of collagen fiber and enhance vascular formation, collectively accelerating wound healing. Overall, this biocompatible nanoplatform is provided as a reliable approach to solve the long-standing problem of infected wound healing.
研究领域:
纳米技术
·
生物医学工程
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药学
·
伤口愈合
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Rui Ni,Lele Huang,Zhen Li,Wenli Zhang,Yajie Wang,Yan Shen,Jianxin Wang,Weigen Lu
Purpose To enhance tumor penetration by formulation design and tumor microenvironment (TME) modulation, herein a novel reactive oxygen species (ROS)-responsive size/shape transformable lipid-polymer hybrid nanoparticle (LPN) has been fabricated for the co-delivery of an anticancer and collagen-inhibition drug. Methods A ROS-responsive poly(D, L-lactide)-thioketal-polyethylene glycol (PLA-TK-PEG) co-polymer was synthesized. LPNs were then fabricated by encapsulation of losartan (LST)-loaded micelles as the core to support paclitaxel (PTX)-loaded liposomes. The PEG content in the lipid shell of LPNs was then adjusted to obtain the size-/shape-transformable LPNs (M/LST-Lip/PTX-PEG 5% ). The ROS-responsiveness was observed in vitro by transmission electron microscopy and the tumor-penetration of the LPNs was evaluated in 3D tumor spheroids by confocal laser scanning microscopy. Tumor-targeting, tumor-penetrating, and antitumor efficacies of the NPs in 4T1 tumor-bearing mice were determined by in vivo imaging. Results ROS-responsive micellar core degradation and the transformation of spherical LPNs (120nm) to smaller 40 mm discoid nanoparticles (NP) were observed. The transformable LPNs exhibited enhanced capacity of penetration in contrast to the un-transformable preparations in three-dimensional (3D) tumor spheroids. Furthermore, synergetic penetrating enhancement was achieved by LST-loaded transformable LPNs in 4T1 and fibroblast cell mixed 3D tumor spheroids. The improved tumor penetration of LST-loaded transformable LPNs was observed in vivo, which could be due to their collagen inhibiting and size/shape transformable effect. Due to their enhanced penetrability, LST and PTX-loaded transformable LPNs demonstrated significant in vivo antitumor efficacy in comparison to other preparations. Conclusion The results confirmed the efficacy of M/LST-Lip/PTX-PEG 5% in tumor targeting, collagen inhibition in TME, and enhanced tumor penetration. This novel drug delivery system can therefore play a substantial role in improving the therapeutic efficacy of antitumor drugs combined with TME-improving agents.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Yu Li,Rong Wang,Lian Xue,Yilin Yang,Feng Zhi
Background Ischaemic stroke is a lethal cerebrovascular disease that occurs worldwide. Astilbin is a natural flavonoid compound with various physiological activities. The purpose of this study was to investigate the neuroprotective effects of Astilbin after cerebral ischaemia reperfusion (I/R) injury. Methods The oxygen and glucose deprivation (OGD) model was used to simulate cerebral I/R injury in vitro . Cell viability was measured via CCK-8 and LDH release assays. Cell apoptosis was measured via Hoechst 33258 staining and flow cytometry assays. ROS was detected via flow cytometry assay. The protein expression levels were determined by western blotting. The middle cerebral artery occlusion (MCAO) model was used to simulate cerebral I/R injury in vivo . Cerebral ischaemic volume was measured by TTC staining. The Zea-Longa score, rota-rod test, and foot-fault test were used to evaluate behavioural changes and neurological deficits in rats. Results Astilbin significantly enhanced cell viability and decreased LDH release after OGD treatment in vitro . Astilbin effectively curbed cell apoptosis induced by OGD via inhibiting the activation of caspase-3, decreasing the ratio of Bax/Bcl-2 and decreasing FADD. Astilbin also inhibited OGD-induced inflammation by suppressing ROS-NLRP3 inflammasome axis activation. Further results revealed that Astilbin could suppress the MAPK pathway and activate the PI3K/AKT pathway. Finally, Astilbin significantly reduced the cerebral infarction volume and relieved neurological deficits in rats in vivo . Conclusion Astilbin could defend against cerebral I/R injury by inhibiting apoptosis and inflammation via suppressing the MAPK pathway and activating the AKT pathway.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2017
·
IF 2.466
Menglu Zhou,Shuying Shen,Xin Zhao,Xingguo Gong
Autophagy has attracted a great deal of interest in tumour therapy research in recent years. However, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on autophagy remains poorly understood in human lung cells. In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation , inducing G 0 /G 1 phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells. Interestingly, luteoloside induced autophagy in lung cancer cells, which was correlated with the formation of autophagic vacuoles, breakdown of p62, and the overexpression of Beclin-1 and LC3-II, but not in a human bronchial epithelial cell line (BEAS-2B). Notably, pretreatment of cancer cells with 3-MA, an autophagy inhibitor, protected against autophagy and promoted cell viability but not apoptosis. To further clarify whether luteoloside-induced autophagy depended on the PI3K/AKT/mTOR/p70S6K signalling pathway , a major autophagy-suppressive cascade, cells were treated with a combination of AKT inhibitor (LY294002) and mTOR inhibitor (Rap). These results demonstrated that luteoloside induced autophagy in lung cancer cell lines by inhibiting the pathway at p -Akt (Ser473), p -mTOR and p-p70S6K (Thr389). Moreover, we observed that luteoloside-induced cell autophagy was correlated with production of reactive oxygen species (ROS). NAC-mediated protection against ROS clearly implicated ROS in the activation of autophagy and cell death. In addition, the results showed that ROS served as an upstream effector of the PI3K/AKT/mTOR/p70S6K pathway. Taken together, the present study provides new insights into the molecular mechanisms underlying luteoloside-mediated cell death in NSCLC cells and supports luteoloside as a potential anti-cancer agent for targeting NSCLC through the induction of autophagy, inhibition of proliferation and PI3K/AKT/mTOR/p70S6K signalling.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
研究领域:
分子生物学
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细胞生物学
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儿科
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肠道生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Kaiqing Yun,Juntong Guo,Renfang Zhu,Tianyi Wang,Xiaoyan Zhang,Hao Pan,Weisan Pan
Combining chemotherapy with photothermal therapy (PTT) for cancer treatment could overcome the inherent limitations of both single-modality chemotherapy and PTT. However, the obstacle of accurate drug delivery to tumor sites based on chemo-photothermal remains challenging. This article describes development of a reactive oxygen species (ROS)-responsive hyaluronic acid-based nanoparticle to overcome these drawbacks. Herein, HA-TK-MTX (HTM) was synthesized by a ROS-responsive cleaved thioketal moiety linker (TK) of methotrexate (MTX) and hyaluronic acid (HA). Through hydrophobic interaction and π–π stacking interaction, a photothermal agent IR780 was integrated into the HTM, and the IR780/HTM nanoparticles (IHTM NPs) were obtained. The IHTM NPs show high photostability, excellent photothermal performance, remarkable tumor-targeting ability, and ROS sensibility. Due to the accurate drug delivery ability and superior chemo-photothermal treatment effect of IHTM NPs, the tumor inhibition rate reached 70.95% for 4T1 tumor-bearing mice. This work serves as a precedent for the chemo-photothermal therapy of cancer by rationally designing ROS-responsive nanoparticles.
研究领域:
纳米技术
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癌症研究
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 6
·2202150
·
IF 11.092
Ying Chen,Zengqiu Yang,Sibu Wang,Qin Ma,Lingyan Li,Xingjie Wu,Qianqian Guo,Ling Tao,Xiangchun Shen
Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton reaction-based reactive oxygen species (ROS) generation recently attracts increasing attention in cancer therapy. However, the lysosomal membranes are protected by highly glycosylated membrane proteins and several endolysosomal damage-response mechanisms can rapidly repair the injured lysosomes. To produce sufficient ROS and cause complete lysosomal membranes rupture, a lysosome-targeted ROS inducer, N -(3-Aminopropyl) morpholine grafted cross-linked lipoic acid vesicles with vitamin C-loading (VC@ N3AM cLAVs), is developed. VC@ N3AM cLAVs efficiently accumulate in lysosomes and convert into two redox couples LA/DHLA (dihydrolipoic acid, reduced form of LA) and VC/DHA (dehydroascorbic acid, oxidized form of VC) by the lysosomal glutathione, which can not only produce a large amount of H 2 O 2 by pro-oxidant action but also accelerate iron transformation through the cyclic redox reactions between each other and cause the efficient conversion of the generated H 2 O 2 into highly toxic •OH. Both in vitro and in vivo experiments demonstrate that VC@ N3AM cLAVs can effectively enhance ROS production and boost LMP, finally initiation irreversible death of tumor cells via ferroptosis pathway, thus representing a potential anticancer drug for cancer therapy.
研究领域:
癌症生物学
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药学
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治疗学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 39
·8253-8262
·
IF 6.331
Yali Chen,Yujun Cai,Xingsu Yu,Hong Xiao,Haozhe He,Zecong Xiao,Yong Wang,Xintao Shuai
Reactive oxygen species (ROS) mediated tumor therapy strategies have exhibited great prospects and attracted increasing attention, among which photodynamic therapy (PDT) has been well-established. However, the anticancer effects of PDT are greatly limited by the hypoxic tumor microenvironment (TME). Hence, exploring a therapeutic strategy that can relieve tumor hypoxia is regarded as the key to overcoming this problem. Herein, we develop a novel nano-enzyme (MnO2@TPP-PEG) that can accurately conduct tumor-specific catalysis of H2O2 to produce oxygen through a Fenton-like reaction, leading to an enhanced PDT under the irradiation of light. More importantly, the process of catalyzing H2O2 decomposition at the tumor location can also generate a cytotoxic hydroxyl radical (˙OH), achieving an excellent chemodynamic therapy (CDT) to enhance the ROS mediated anti-cancer effect. Notably, the nano-enzyme exerts a high loading content of the photosensitizer, which minimizes the side effects probably caused by the vector.
研究领域:
癌症研究
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纳米技术
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治疗策略
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chen Xu,Rijin Song,Pei Lu,Jianchun Chen,Yongqiang Zhou,Gang Shen,Minjun Jiang,Wei Zhang
Introduction Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment.Methods Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs).Results The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy.Conclusion Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.
研究领域:
药剂学
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Jie An,Yong-Guo Hu,Kai Cheng,Cheng Li,Xiao-Lin Hou,Gang-Lin Wang,Xiao-Shuai Zhang,Bo Liu,Yuan-Di Zhao,Ming-Zhen Zhang
Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2020
·Vol. 37
·期 5
·2000021
·
IF 3.099
Ali Maruf,Yi Wang,Li Luo,Yuan Zhong,Deti Nurhidayah,Boyan Liu,Dan Tang,Muhammad Abdul Rouf,Haijun Zhang,Yuxia Yin,Wei Wu,Guixue Wang
The development of smart nanoagents that can respond to a specific stimulus has gained remarkable interest for treating various kinds of diseases, including atherosclerosis. On the other hand, a cell camouflaging strategy has been considered as a pivotal factor to improve the delivery stealthiness, biocompatibility, and biodegradability of nanocarriers, resolving the shortcomings of PEGylation. In this study, reactive oxygen species (ROS)-responsive 5-aminolevulinic acid (ALA) prodrug nanostructures (ROSELLA) encapsulating rapamycin (RAP) are blended with nanoerythrocyte membranes to construct red blood cell membrane (RBCM)/RAP@ROSELLA. These nanoagents are designed to be able to escape the biological barriers, accumulate in atherosclerosis lesions, and enhance the release of drugs in the intracellular milieu due to the magnification of hydrogen peroxide (H 2 O 2 ). In vitro study proves its superior ability to inhibit the proliferation of macrophages and vascular smooth muscle cells. In vivo developmental toxicity further confirms that no significant systematic toxicity is induced by RBCM/RAP@ROSELLA, implying its favorable biocompatibility, which has potential for precise nanomedicine to combat atherosclerosis.
研究领域:
纳米技术
·
药学
·
心血管疾病
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Advanced Composites and Hybrid Materials
·
2025
·Vol. 8
·期 4
·1-23
·
IF 21.8
Yin Xiujuan,Xue Shuqin,Ji Jiaqi,Zhao Mingyu,Shao Min,Yin Likang,Zhang Saisai,Liu Lei,Li Bin,Zhang Lei,Li Yuan,Wang Xiao
Liver fibrosis (LF) is a leading cause of liver-related mortality worldwide. Although antifibrotic drugs are commonly used in clinical practice, their efficacy remains limited. Excessive reactive oxygen species (ROS) in the fibrotic liver microenvironment play a crucial role in LF progression. Nanozymes, owing to their enzyme-mimicking catalytic activity and antioxidant properties, offer a promising strategy for LF treatment. Vanadium-based nanozymes exhibit ROS-scavenging capabilities and promote fibrosis reversal, while zirconium (Zr)-based metal–organic frameworks (MOFs), such as UiO-66, possess excellent biocompatibility and catalytic activity. However, the therapeutic efficacy of nanozymes is hindered by their intrinsic catalytic limitations. Ultrasound (US), a non-invasive therapeutic modality, has been shown to enhance nanozyme activity and improve treatment outcomes. In this study, we developed a dual-nanozyme composite (UiO-66/V 2 C/L-Arg/pPB, UVLp) with targeted ROS-scavenging and L-arginine (L-Arg) delivery capabilities. Upon ultrasound exposure, UVLp releases L-Arg and nanozymes, facilitating nitric oxide (NO) generation, alleviating oxidative stress, and mitigating liver fibrosis. This work introduces a novel ultrasound-activated nanozyme platform for LF therapy, providing valuable insights for clinical translation.
研究领域:
纳米医学
·
肝病学
·
诊疗一体化
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生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）