ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Zhongxi Xie,Shuang Liang,Xuechao Cai,Binbin Ding,Shanshan Huang,Zhiyao Hou,Ping’an Ma,Ziyong Cheng,Jun Lin
Hypoxia and overexpression of glutathione (GSH) are typical characteristics of the tumor microenvironment, which severely hinders cancer treatments. Here, we design a novel biodegradable therapeutic system, O2–Cu/ZIF-8@Ce6/ZIF-8@F127 (OCZCF), to simultaneously achieve GSH depletion and O2-enhanced combination therapy. Notably, the doped Cu2+ doubles the O2 storage capacity of the ZIF-8 matrix, which makes OCZCF an excellent pH-sensitive O2 reservoir for conquering tumor hypoxia, enhancing the photodynamic therapy (PDT) efficiency of chlorin e6 (Ce6) under 650 nm laser irradiation. Moreover, the released Cu2+ can act as a smart reactive oxygen species protector by consuming intracellular GSH. The byproduct Cu+ will undergo highly efficient Fenton-like reaction to achieve chemodynamic therapy (CDT) in the presence of abundant H2O2. The accompanying O2 will further alleviate hypoxia. The in vitro and in vivo experimental data indicate that OCZCF could cause remarkable tumor inhibition through enhanced synergetic PDT and CDT, which may open up a new path for cancer therapy.
研究领域:
癌症研究
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纳米技术
·
生物医学工程
·
药学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Lifeng Hang,Hailiang Li,Tao Zhang,Dandan Men,Cong Zhang,Peng Gao,Qianling Zhang
Recently, the chemodynamic therapy (CDT) has been widely reported and applied to tumor therapy. However, only low level hydroxyl radicals (•OH) generated by the endogenous hydrogen peroxide alone are insufficient to kill the cancer cells. To overcome the insufficient therapeutic effect, this study reports a novel CDT based on Fenton catalyst Au@Prussian blue nanocubes (Au@PB NCs), subsequently encapsulated with doxorubicin (Dox). The in vitro and in vivo results indicate that the Dox-Au@PB NCs can take synergistic effects on tumor suppressor by CDT. In addition, Au@PB NCs possess high X-ray computed tomography contrast enhanced efficiency about ∼27.13 HU·mL·mg–1. This study highlights a great potential of the Dox-Au@PB NCs for tumor diagnosis and CDT.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2020
·Vol. 82
·期 3
·404-411
·
IF 1.902
Xiaolong Sun,Xu Wang,Zhenyu Zhao,Jing Chen,Cheng Li,Gang Zhao
Diabetic foot ulcer (DFU) is an invariably common complication of diabetes, characterized by delayed wound healing process and increased inflammation. Evidence has indicated that paeoniflorin exerts an anti-inflammatory effect in diabetic retinopathy. The current work was aimed to investigate the effect of paeoniflorin on inflammation and wound healing in DFU. DFU rat models by streptozotocin and skin biopsy punch, as well as high glucose-treated human immortalized keratinocytes (HaCaT) were established. Levels of blood glucose, wound contraction and proinflammatory cytokine were detected after paeoniflorin administration. Several essential targets associated with the NF-κB and Nod-like receptor protein-3 (NLRP3) signaling pathways were examined. Results showed markedly down-regulation of interleukin (IL)-1β, IL-18 and tumor necrosis factor-alpha in paeoniflorin-treated DFU rats. Paeoniflorin decreased the expression levels of chemokine receptor CXCR2, nuclear NF-κB and p-IκB (Ser36), as well as increased IκB level. Histological analysis and immunostaining showed lower inflammatory cells with decreased NLRP3 and cleaved caspase-1 levels following paeoniflorin treatment. Further in vitro evidence confirmed that paeoniflorin efficiently inhibited NLRP3 and NF-κB-mediated inflammation in DFU by inhibiting CXCR2. These findings are suggestive of greatly attenuated wound inflammation and better wound healing in paeoniflorin-treated DFU rats. Our study demonstrates that paeoniflorin is a potential therapeutic agent for DFU.
研究领域:
药理学
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糖尿病
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炎症研究
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伤口愈合
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DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 85
·期 4
·786-797
·
IF 1.516
Wang Yuanyuan,Guo Shanqi,Jia Yingjie,Yu Xiaoyu,Mou Ruiyu,Li Xiaojiang
Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Wei Wei,Yuanyuan Yao,Hongyuan Bi,Wenxin Xu,Yan Gao
Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro . Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress , which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21–5p (miR-21–5p). The expression of miR-21–5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21–5p overexpression reversed the effects on cell viability , inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21–5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.
研究领域:
分子生物学
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细胞生物学
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肾脏病学
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DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-PLANT
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2021
·Vol. 57
·期 3
·372-379
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IF 2.252
Li Xiuyu,Zhang Zijie,Ren Yunhui,Feng Yue,Guo Qi,Dong Li,Sun Yuhan,Li Yun
Tetraploid black locust ( Robinia pseudoacacia L.) has advantages over diploid varieties in growth and stress resistance. Previous studies had shown that tetraploid black locust can be induced only by treating shoot tips of the germinating seeds with colchicine. In order to establish a simpler and more efficient tetraploid induction method in black locust, we induced tetraploid plants by treating the hypocotyls from in vitro –grown seedlings with different concentrations of colchicine, and then provided a method for tetraploid identification based on stomatal size and density in this study. The highest induction efficiency was 53.33% by treating hypocotyl explants with 70 mg·L −1 colchicine for 2 d. Tetraploid black locust was significantly different from diploid in morphological characteristics. Leaf area, leaf thickness, chlorophyll content, stomatal length, and stomatal width were greater in tetraploid plants than in diploid plants, whereas the opposite was true for leaf aspect ratio, stomatal index, and stomatal density. The differences in stomatal size and density between diploid and tetraploid were nearly two times; therefore, size and density of stomata can be used as a stable and distinct marker to rapidly screen tetraploids. The results of this study suggested that the hypocotyl was an ideal material to induce tetraploid black locust in vitro and confirmed that stomatal size and density could be an effective and reliable marker to identify ploidy level in black locust.
研究领域:
植物科学
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生物技术
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分子生物学
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
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IF 5.268
Qiang Li,Dongsheng Fu,Jie Zhang,Hong Yan,Huifang Wang,Baolong Niu,Ruijie Guo,Yiming Liu
In this study, a new type of polypeptide, crosslinked methoxy poly(ethylene glycol)-g-poly(aspartic acid)-g-tyrosine (CPPT), was synthesized via a green and simple one-pot polymerization method. With the disulfide-crosslinked interlayer and the CaP shell, the pH and redox dual-sensitive polypeptide-based organic-inorganic hybrid nanoparticles encapsulated curcumin (Cur) into the hydrophobic core of micelles and loaded doxorubicin hydrochloride (DOX) on the hydrophilic segment of micelles as well as CaP shell. The spherical Cur- and DOX-loaded nanoparticles (CPPT@CaP-CD) showed a hydrodynamics size of about 157.9 ± 3.9 nm. The premature leakage of drugs from the nanoparticles at physiological pH was efficiently restrained because of the enhanced structure integrity, whereas at acidic and hypoxia microenvironment the release of both drugs was promoted due to the rapid dissolution of the CaP shell and the break of the disulfide crosslinked network, facilitating the stimuli-responsive controllable drugs release. In vitro anticancer activity evaluation revealed that the co-loaded nanoparticles presented higher cytotoxicity against A549 cells compared with that of the free combination of Cur + DOX. Confocal laser scanning microscopy observation indicated that more DOX and Cur were released into the nucleus triggered by the up-regulated intracellular glutathione (GSH) concentration and decreased pH, displaying enhanced cell uptake. The self-assembling polypeptide-based dual-sensitive drug co-delivery system could be a promising platform for efficient chemotherapy.
研究领域:
生物材料学
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药物递送系统
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 7
·2005865
·
IF 13.281
Peipei Yang,Jia Tao,Fengfeng Chen,Yuying Chen,Jiaqi He,Kui Shen,Peng Zhao,Yingwei Li
Nanozyme-based chemodynamic therapy (CDT) has emerged as an effective cancer treatment because of its low side effects and without the requirement of exogenous energy. The therapeutic effect of CDT highlights the pivotal importance of active sites, H 2 O 2 supplement and the glutathione (GSH) depletion of a nanozyme. The construction of a single kind of catalyst with multiple functions for the enhanced CDT is still a big challenge. In this work, seven types of bimetallic nanoparticles are synthesized using a metal–organic framework (MOF) as a stable host instead of a Fenton or Fenton-like ions supplier. Among them, Cu-Pd@MIL-101 with an alloy loading of 9.5 wt% modified by PEG (9.5% CPMP) is found to exhibit the highest peroxidase (POD) like activity combined with a superoxide dismutase (SOD) mimic activity and the function of GSH depletion. The in vivo results suggest that the stable and ultrafine nanoparticles possess favorable CDT effect for tumor and good biosafety as well as biocompatibility. This work has provided a credible strategy to construct nanozymes with an excellent activity and may pave a new way for the design of enhanced tumor CDT treatment.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2021
·
IF 2.646
Qiang Li,Dongsheng Fu,Jie Zhang,Tianyang Li,Huifang Wang,Wenjuan Hou,Baolong Niu,Ruijie Guo,Yiming Liu
Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. In vitro anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.
研究领域:
药剂学
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肿瘤学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Wu Xiaodong,Li Pengpeng,Cheng Jian,Xu Qiang,Lu Beiji,Han Conghui,Huo Weiling
Objective: Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs.Methods: We synthesize and assemble a hydrogen peroxide [H2O2, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation.Results: The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under H2O2 stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes.Conclusion: This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.
研究领域:
药学
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生物医学工程
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骨科
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纳米技术
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产品关联
DOI
PubMed
高影响因子
BMC CANCER
·
2021
·Vol. 21
·期 1
·1-14
·
IF 4.43
Zhao Wei,Zhao Jing,Guo Xiao,Feng Yujie,Zhang Bingyuan,Tian Lantian
Background Cholangiocarcinoma is a common malignant tumor of digestive system. LncRNA metallothionein 1 J, pseudogene (MT1JP) has been reported to play tumor-suppressing roles in multiple cancers. However, its effect on cholangiocarcinoma has not been evaluated. Methods The expression of MT1JP in intrahepatic cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into intrahepatic cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xenograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude mice. Results MT1JP was downregulated in intrahepatic cholangiocarcinoma specimens, and its expression was related with TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in intrahepatic cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in intrahepatic cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice. Conclusions MT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axis. These findings may provide novel insights for clinical diagnosis and treatment of cholangiocarcinoma.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2021
·
IF 2.466
Yujie Jia,Yu Tong,Lianqiu Min,Yanrong Li,Yan Cheng
NOD-like receptor protein 3 (NLRP3) inflammasome is tightly related to the pathogenesis of cerebral ischemia/reperfusion (I/R) injury, and oridonin (Ori) has shown the potential to alleviate ischemia/reperfusion injury with underlying mechanisms. Our study aims to figure out whether Ori protects against the cerebral ischemia/reperfusion injury by the NLRP3 inflammasome signaling. In this study, a temporary middle cerebral artery occlusion (MCAO) and reperfusion surgery was conducted on male C57BL/6 mice to mimic cerebral I/R injury in vivo. Cellular model of cerebral I/R in vitro was achieved by oxygen-glucose deprivation and reintroduction (OGD/R) in BV2 microglia cells. We found that Ori treatment significantly relieved the neurological deficits, neuronal injury and microglia activation in I/R mice according to morphological and histological analyses. Meanwhile, the inactivation of NLRP3 inflammasome was determined in Ori-treated mice with significantly down-regulated expressions of inflammasome-related genes. Western-blot analysis further demonstrated the negative effect of Ori on NF-κB signaling with diminished phosphorylation and degradation of IκBα as well as suppressed translocation of p65. Furthermore, we indicated that Ori suppressed the activation of NLRP3 inflammasome in OGD/R induced BV2 microglia cells by inhibiting NF-κB signaling. In summary, our findings make Ori a potential candidate for therapy of cerebral I/R injury in the future.
研究领域:
神经科学
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
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