CELLULAR SIGNALLING
·
2016
·
IF 4.191
Wenjun Zhao,Aiyun Li,Xin Feng,Ting Hou,Kang Liu,Baolin Liu,Ning Zhang
This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10 days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin . Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B . Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment.
研究领域:
药理学
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内分泌学
·
代谢学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 187
·期 1
·1-11
·
IF 5.479
Wang Qian-Long,Huang Wei-Xue,Zhang Pu-Juan,Chen Li,Lio Chon-Kit,Zhou Hua,Qing Lin-Sen,Luo Pei
An ultra-sensitive method is described here for the determination of HIF-1α (an early biomarker for myocardial infarction) in circulating exosomes in serum. Gold nanospheres were functionalized with a HIF-1α-binding aptamer via sulfydryl chemistry. The apt-AuNP-coated gold seeds were grown by seed-mediated growth, and this significantly increased the peroxidase-mimicking property the nanoparticles. A chromogenic system composed of 3,3′5,5′-tetramethylbenzidine and hydrogen peroxide was used. Absorbance at 652 nm increases linearly in the 0.3 to 200 ng L −1 HIF-1α concentration range, and the limit of detection is 0.2 ng L −1 . The method was tested by analyzing rat serum from isoproterenol (ISO)-induced myocardial infarction. It allows HIF-1α to be directly determined in a 25 μL sample without preconcentration. The assay is not interfered by the polydispersity of exosomes released under either health and disease conditions.
Gold nanospheres were functionalized with a HIF-1α-binding aptamer via sulfydryl chemistry. Nanosized gold seed particles were then modified with the functionalized gold nanospheres, and this strongly increases the peroxidase-mimicking activity of the nanomaterial. By using the tetramethylbenzidine/H 2 O 2 chromogenic system, the absorbance at 652 nm increases linearly in the 0.3 to 200 ng L -1 HIF-1α concentration range.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yan Chen,Ming Zhang,Zhifang Liu,Ning Zhang,Qingpeng Wang
Tumor microenvironment (TME) is a pivotal factor driving the tumor metastasis and leading to the failure of tumor therapy. Here, a series of ursodeoxycholic acid platinum(IV) conjugates with potency in remodeling the TME through suppressing JAK2/STAT3 signaling was developed. A candidate was screened out, which displayed potent antiproliferative and antimetastatic performance both in vitro and in vivo. It displayed superior pharmacokinetic properties compared to cisplatin. Serious DNA injury was induced, and then mitochondria-mediated apoptosis was initiated through the Bcl-2/Bax/Caspase3 pathway. The JAK2/STAT3 and TGF-β1 signaling pathways were remarkably inhibited, and pro-death autophagy was subsequently promoted. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.
研究领域:
肿瘤学
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药理学
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分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Chang Liu,Yuanyuan Zhang,Jing Wen,Ji Liu,Meirong Huo,Yan Shen,Hao Luo,Hui Zhang
Radio-photothermal therapy is an effective modality for cancer treatment. To overcome the radio-resistance in the hypoxic microenvironment and improve the sensitivity of radiotherapy, metal nanoparticles, and radio-photothermal therapy are widely used in the research of improving the curative effect and reducing the side effects of radiotherapy. Here, we developed red blood membrane camouflaging bismuth nanoflowers (RBCM-BNF) with outstanding physiological stability and biodegradability for lung tumours. In vitro data proved that the RBCM-BNF had the greatest cancer cell-killing ability combined with X-ray irradiation and photo-thermal treatment. Meanwhile, in vivo studies revealed that RBCM-BNF can alleviate the hypoxic microenvironment and promote tumour cell apoptosis by inhibiting HIF-1α expression and increasing caspase-3 expression. Therefore, RBCM-BNF had a good radio-sensitizing effect and might be a promising biomimetic nanoplatform as a therapeutic target for cancer.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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放射学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jin Cui,Gongzheng Wang,Li Xian Yip,Mengzhen Dong,Mengyao Mu,Liya Tian,Yuan Gao,Qing Fan,Qiang Zhu,Xinya Zhao,Xueli Xu,David Tai Leong,Xiao Sun
Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin-manganese interaction by nanoplatinum growth, a novel ferritin-platinum-manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree-dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram-based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase-like activity can catalyze the generation of O 2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF-1α, blocking the TGF-β1/Smad signaling pathway. In addition, metformin shows synergy with HIF-1α reduction in blocking the TGF-β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real-time anti-fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti-fibrotic therapy with real-time monitoring.
研究领域:
医学影像
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纳米技术
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药理学
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分子生物学
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治疗学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yun Zeng,Yonghua Zhan,Xinyue Liu,Jingwen Ma,Huifang Liu,Hanrui Li,Tong Yi,Qingxia Zhu,Getao Du,Linfei Zhao,Dan Chen,Xueli Chen
Tumor metastasis is a major cause of poor cancer prognosis. Photothermal therapy (PTT) is a non-invasive, non-oxygen-dependent, and highly spatiotemporally precise treatment that may aid chemotherapy in suppressing tumor growth and metastasis. This article aims to develop and modify a CuS-based nanoplatform linking RGD-Acrk to actively target and internalize doxorubicin (DOX) into tumor cells, resulting in an alternating strategy of synergistic chemo/PTT. The nanoparticle’s shape, spectra, drug encapsulation efficiency, loading content, and controlled release are characterized, and a comparison of 808/980 nm lasers is used to irradiate the nanoplatform. The cell survival rate is used to determine the cytotoxicity of DOX and PTT, and the chemo/PTT is used to treat 4T1-Luc tumor-bearing mice. Simultaneously, bioluminescence and photoacoustic imaging are employed to assess therapy efficacy, as well as tumor size, weight, density, the bodyweight of mice, and survival curves. H&E, immunohistochemistry for HIF-1α, and TUNEL fluorescence staining confirm these findings, suggesting that the nanoplatform has a good active-targeted capacity and perform high-efficiency PTT caused by 980 nm laser irradiation. The synergistic effect is at least 3.53 times higher than chemo/PTT without synergistic effect and tumor liver metastasis is successfully suppressed, showing that it has the potential to be used for cancer treatment and prognosis improvement.
研究领域:
肿瘤学
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纳米技术
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诊疗学
✓ 已验证
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Huang Zhusheng,Huang Shiqian,Song Simin,Ding Yankui,Zhou Hao,Zhang Shaoyin,Weng Lixing,Zhang Ying,Hu Yiqiao,Yuan Ahu,Dai Yunlu,Luo Zhimin,Wang Lianhui
The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T 2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫治疗
·
放射治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Liya Feng,Yuanxin Wang,Xiangyue Wang,Baochan Li,Yifan Liu,Wanying Zhang,Jianbo Ji,Lijun Shao,Xiuli Guo
In the tumor microenvironment (TME), tumor associated macrophages (TAMs) often exhibit a preference for M2-like phenotype, which supports tumor progression under hypoxia. The underlying mechanisms driving the behavior of hypoxic TAMs are highly complex. Recently, exosomal long non-coding RNAs (lncRNAs) derived from non-cancerous cells within TME have attracted more attention from researchers. In the present study, we investigated the function of exosomal lncRNA MIR210HG derived from hypoxic TAMs in triple negative breast cancer (TNBC). Results showed that MIR210HG was significantly upregulated in hypoxic TAMs, their exosomes, and exosomes-treated TNBC cells. When MIR210HG was suppressed, the expression of M2-polarization markers and proteins associated with the PI3K/Akt/mTOR pathway in hypoxic TAMs was notably inhibited. Moreover, the suppression of TAM-derived exosomal MIR210HG effectively inhibited the migration, invasion and vasculogenic mimicry (VM) formation of TNBC cells. Notably, dual inhibition of both exosomal and endogenous MIR210HG in tumor cells synergistically restricted TNBC metastasis of in vivo . Mechanistically, we elucidated that MIR210HG promoted the malignant phenotypes of TNBC by upregulating the expression of HIF-1α protein, which in turn initiated RASSF7 transcription, resulting in the promotion of epithelial-mesenchymal transition (EMT) process. Collectively, our results identified MIR210HG as a key molecule mediating exosome-based communication from hypoxic TAMs to TNBC cells and revealed its pro-metastatic role, Consequently, MIR210HG emerges as a highly promising therapeutic target of TNBC.
研究领域:
癌症生物学
·
分子生物学
·
免疫学
·
细胞生物学
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遗传学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 32
·期 42
·425101
·
IF 3.874
Qing Zhang,Lian Wu,Shaozheng Liu,Qingjie Chen,Lingpeng Zeng,Xuezhong Chen,Qing Zhang
Photodynamic therapy (PDT) and immunotherapy have been often adopted for ovarian cancer therapy, yet their application is limited by the high recurrence rate and toxic side effects. Intriguingly, nanoparticles contribute to enhancing the performance of PDT. Here, we investigated the synthesis of HER-2-Nanobody (Nb)-conjugated human serum albumin (HSA) incorporated with chlorin (Ce6) and catalase (CAT) (Nb@HCC), and analyzed the synergic effect of Nb@HCC-mediated PDT and immunotherapy for SK-OV-3 tumors. The Ce6 and CAT were incorporated into HSA to construct the HCC nanoparticles. HER-2-Nanobody was the purified bacterial crude extract, and conjugated with HCC to prepare Nb@HCC via heterodisulfide. The effects of Nb@HCC with near infrared ray (NIR) irradiation on moderating hypoxia and hypoxia inducible factor-1α (HIF-1α) expression were evaluated in the SK-OV-3 cells and tumor tissues. A SK-OV-3 tumor-bearing model was developed, where the synergistic effect of Nb@HCC-mediated PDT and anti-CTLA-4 therapy was investigated. Nb@HCC with a 660 nm laser irradiation could induce massive reactive oxygen species and trigger apoptosis in SK-OV-3 cells. Nb@HCC and PDT promoted danger-associated molecular patterns (DAMPs), which indicated immunogenic cell death and maturation of dendritic cells in the SK-OV-3 cells. Irradiated by NIR, Nb@HCC alleviated the hypoxia and decreased the expression of HIF-1α. The Nb@HCC-mediated PDT and anti-CTLA-4 therapy synergically inhibited the progression of distant tumor, and induced T cell infiltration. Biosafety tests suggested that Nb@HCC would not cause damage to the major organs with less toxicity and side effects. To conclude, a combination of Nb@HCC-mediated PDT and anti-CTLA-4 therapy could inhibit the progression of distant tumor to attain remarkable therapeutic outcomes.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
药学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Zhi-Hang He,Han-Xiao Tang,Yan-Zheng Pan,Min Cen,Zhi-Juan Zhang
The oxygen consumption during chemodynamic therapy (CDT) can lead to severe cellular hypoxia, resulting in an increase in the hypoxia inducible factor-1α (HIF-1α) level, which hinders the effectiveness of CDT and induces tumor metastasis. Here, we propose a strategy of synergistic therapy between CDT and the HIF-1α inhibitor to avoid the limitations of CDT and reduce the risk of metastasis. Herein, based on the coordination between Fe3+ and apigenin (API, HIF-1α inhibitor), we constructed a hyaluronic acid (HA)-modified API-Fe nanoparticles (AF@HA NPs) for synergetic chemotherapy and glutathione (GSH)-activated self-enhancing CDT. AF@HA NPs have high drug loading capacity, stability, and biocompatibility. Furthermore, the overexpressed GSH in cancer cells can reduce Fe3+ to Fe2+, weakened the coordination between API and Fe, and promoted the release of API for chemotherapy. Fe2+ could react with endogenous H2O2 to generate hydroxyl groups for CDT. In addition, the released API could inhibit the expression of HIF-1α and increase the sensitivity of cells to reactive oxygen species (ROS), thereby achieving a synergistic effect between self-enhancing CDT and chemotherapy. The results of in vitro and in vivo experiments indicated that AF@HA NPs could effectively inhibit tumor growth and suppress the lung metastasis of tumor cells.
研究领域:
纳米技术
·
癌症治疗
·
药理学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today
·
2024
·
IF 21.1
Yao Yang,Xiaotong Liang,Qimanguli Saiding,Jiachan Lin,Jinyuan Li,Wenyan Wang,Ping Huang,Li Huang,Wenfeng Zeng,Jinhai Huang,Hongzhong Chen,Wei Tao,Xiaowei Zeng
Photodynamic therapy (PDT) can enhance immune checkpoint blockade (ICB) antitumor immunity. However, PDT can significantly exacerbate the hypoxic tumor microenvironment and stimulate tumor neovascularization, promoting tumor invasion and metastasis. Camptothecin can inhibit angiogenesis by down-regulating hypoxia-inducible factor 1α (HIF-1α). Therefore, this study proposed to combine camptothecin with PDT for the first time to alleviate the disadvantage of PDT, and play its dual role of chemotherapy and antiangiogenesis. Here, a light-activated nanocarrier crosslinked the anti-PD-L1, photosensitizer, and camptothecin prodrug mildly with a thioketal bond for checkpoint blockade immunoregulation was designed. Firstly, photosensitizer-induced PDT and immunogenic cell death effect significantly increase T cell infiltration (33.3 % CD8 + increase), enhancing ICB antitumor immunity. Secondly, the antiangiogenic effect of camptothecin was beneficial for alleviating hypoxic tumor microenvironment exacerbated by PDT (HIF-1α expression decreased in tumor cells). Thirdly, light-activated release facilitates tumor accumulation (3.22 times) and controlled drug release. Thus, the immune checkpoint blockade combined with PDT and an antiangiogenic therapy of camptothecin creates a positive feedback co-delivery platform that exemplifies cascaded synergistic tumor therapy by checkpoint blockade immunoregulation. Besides, it also introduces a new strategy for combining small molecule drugs with macromolecules like proteins to treat various diseases.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Min Chen,Tao Liu,Wenqiang Li,Yingting Li,Puxin Zhong,Huanchen Yan,Jingyin Kong,Weixiang Liang
Background Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.Methods A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.Results A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.Conclusion The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.
研究领域:
生物医学工程
·
纳米技术
·
组织工程
·
再生医学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）