EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Fangjie Wang,Lairong Song,Qianqian Xu,Ang Jia,Xiangwei Meng,Hongfei Jiang,Renshuai Zhang
Hypoxia is a common feature of various solid tumors, which reduces the sensitivity of tumor cells to both radiotherapy and chemotherapy. However, hypoxia also presents an opportunity for tumor-selective therapy. The prodrug strategy, leveraging the hypoxic nature of the tumor microenvironment, shows significant potential for clinical application. Here we present CHD-1 , a hypoxia-activated antitumor prodrug that activates in hypoxic environments, effectively inhibiting hypoxic tumor cells while exhibiting no toxicity to normoxic cells. CHD-1 impairs mitochondrial morphology and membrane potential of hypoxic tumor cells, further triggers excessive mitophagy and induces apoptosis. Moreover, prodrug CHD-1 significantly inhibits HeLa xenograft growth in vivo , and shows lower toxicity than parent molecule in an acute toxicity assessment in animal models. This study introduces a promising hypoxia-activated antitumor prodrug with strong potential for further development in hypoxic tumor therapy.
研究领域:
肿瘤学
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药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Lijuan Jia,Xuejin Yang,Kaiqiang Hu,Jiayu Feng,Fang Wang,Kai Li,Xin Sun,Fei Wang,Ping Ning
In this study, we prepared high-performance copper-modified adsorbent (XCu@TiO 2 ) via a simple and low-cost strategy to achieve efficient removal of PH 3 under anaerobic conditions. The effects of copper loading and reaction temperature on the performance of the adsorbent are first investigated, and the experimental results demonstrated that the optimal adsorbent (30Cu@TiO 2 ) had the highest PH 3 breakthrough capacity (135.73 mg(PH 3 )‧g adsorbent -1 ) among all the tested adsorbents. Further characterization analysis confirmed that CuO is the active component of the adsorbent, and the excellent dephosphorization performance is attributed to its abundant alkaline sites, sufficient active oxygen, and developed pore structure. While the consumption of CuO and the accumulation of phosphorus species (H 3 PO 4 , Cu 3 P) on the surface and internal pores of the adsorbent are the main reasons for the deactivation of the adsorbent. Strikingly, the deactivation of the adsorbent converts its active component CuO into the P-type semiconductor Cu 3 P with high added value, implying that the deactivated adsorbent (Cu 3 P/TiO 2 ) is a multifunctional material, and the desulfurization experiments also confirm the reusability of the deactivated adsorbent. Overall, XCu@TiO 2 is a promising and efficient PH 3 adsorbent that can effectively avoid the risk of secondary pollution during the treatment and regeneration of deactivated adsorbents.
研究领域:
环境科学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Physiology
·
2025
·
IF 3.4
Ziqin Wei,Hongfang Mu,Fangfang Qiu,Minghui Zhao,Xiaojing Zhang,Wenbin Li,Hai Jia,Rong Wang
Objective Previous research has demonstrated that the hypoxic environment at high altitudes significantly alters the pharmacokinetics of many drugs, reducing their efficacy and increasing adverse effects. A key factor in this altered drug metabolism is the inhibition of ATP-binding cassette subfamily B member 1 (ABCB1), an efflux transporter protein, in the liver tissues of plateau rats. Rat ABCB1, encoded by the ABCB1A and ABCB1B genes, has two isoforms functionally analogous to human ABCB1. Histone acetylation, an epigenetic mechanism, may regulate ABCB1 transcription in hypoxic conditions by modifying chromatin structure and interacting with signaling pathways. However, its role in ABCB1 transcriptional regulation under hypoxia remains unclear. Based on this, the present study employed the BRL cell line to establish a hypoxia model, aiming to investigate the histone acetylation-mediated regulatory mechanisms of ABCB1 expression under hypoxic conditions, with the ultimate goal of providing novel theoretical foundations for rational drug use in high-altitude regions. Methods Establishment of BRL hypoxia model: BRL cell viability was detected by CCK-8 assay, and HIF-1α expression was measured by RT-qPCR and Western blot. After treating the BRL hypoxia model with HDAC inhibitors, ABCB1 and HDAC5 expression were detected by RT-qPCR, Western blot, and immunofluorescence. Rhodamine 123 accumulation assay was performed to examine the effect of HDAC inhibitors on ABCB1 functional activity. HDAC5 was targeted by siRNA technology to detect ABCB1 and H3K9ac expression. CUT&Tag assay was used to measure H3K9ac levels at the ABCB1 promoter region. After SAHA treatment of the BRL hypoxia model, SP1 expression was detected by RT-qPCR and Western blot. Combined treatment with SAHA and siRNA targeting SP1 was performed to detect ABCB1 expression. Co-immunoprecipitation and fluorescence colocalization assays were conducted to examine interactions among SP1, HDAC5, and ABCB1. Results After hypoxic culture for different durations, cell viability decreased while HIF-1α expression increased, indicating the successful establishment of the BRL hypoxia model. In the BRL hypoxia model, ABCB1 and SP1 expression decreased while HDAC5 expression increased. After SAHA treatment, ABCB1 and SP1 expression were upregulated while HDAC5 was downregulated. Rhodamine 123 accumulation assay showed that SAHA could enhance ABCB1 functional activity by inducing its expression. After HDAC5 was knocked down using siRNA, ABCB1 and H3K9ac expression increased, and ABCB1 functional activity was enhanced. CUT&Tag assay demonstrated that H3K9ac levels at the ABCB1B promoter region decreased in the BRL hypoxia model, while HDAC5 inhibition increased H3K9ac levels at this region. After SP1 was knocked down using siRNA, the inductive effect of SAHA on ABCB1 was blocked. Co-immunoprecipitation and fluorescence colocalization showed interactions among SP1, HDAC5, and ABCB1. Conclusion In BRL cells, HDAC5 may be recruited by SP1 to form a complex, reducing free HDAC5, increasing H3K9ac at the ABCB1B promoter, and activating ABCB1 transcription. In the BRL hypoxia model, disruption of the SP1-HDAC5 complex increased free HDAC5, lowered H3K9ac at the ABCB1B promoter, and suppressed ABCB1 transcription. These results suggest that HDAC inhibitors enhance ABCB1 expression in hypoxic environments, indicating that combining HDAC inhibitors with therapeutic agents could mitigate reduced drug efficacy and adverse effects caused by ABCB1 suppression.
研究领域:
药理学
·
分子生物学
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Mengsi Wu,Chao Chen,Zhiyong Liu,Jia Tian,Weian Zhang
Photodynamic therapy (PDT) has attracted considerable attention, since it could effectively kill bacteria and prevent the development of multi-drug resistance. However, PDT currently suffers from oxygen limitation and hypoxia is a prominent feature of pathological states encountered in inflammation, wounds, and bacterial infections. Herein, an oxygen-tunable nanoplatform based on perfluorocarbon-conjugated tetrafluorophenyl bacteriochlorin (FBC-F) was designed for effective antimicrobial therapy . The introduction of fluorine atoms can not only increase the reactive oxygen species (ROS) production capacity of FBC-F by facilitating the intersystem crossing (ISC) process of FBC photosensitizers , but also make FBC-F deliver more oxygen into the treatment sites benefiting from the outstanding oxygen-dissolving capability of perfluorocarbon . As a consequence, the FBC-F nanoplatform was able to efficiently generate singlet oxygens for type II PDT, as well as superoxide anions and hydroxyl radicals for type I PDT, and significantly improve antibacterial efficacy in vitro. In vivo experiments further proved that the FBC-F with a powerful antibacterial capability could well promote wound healing and destroy biofilm . Thus, this FBC-F nanoplatform may open a new path in photodynamic antibacterial therapy . Statement of significance Photodynamic therapy is a promising antibacterial treatment, but its efficacy is severely compromised by hypoxia . To overcome such a limitation, we constructed an oxygen-regulated nanoplatform ( FBC-F ) by attaching perfluorocarbons (PFC) to the NIR photosensitizer ( FBC ). As an analogue of bacteriochlorin , FBC could generate 1 O 2 through energy transfer , as well as O 2 −· and ·OH through electron transfer for synergistic type I and type II photodynamic antibacterial therapy. Benefiting from the oxygen-dissolving capability of PFC, FBC-F could efficiently deliver more oxygen into the treatment site and alleviate the hypoxic environment. As a consequence, FBC-F could effectively generate large amounts of reactive oxygen species to achieve improved antibacterial efficacy and provide a promising approach for eliminating biofilms.
研究领域:
医学
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微生物学
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药理学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Qin Shi,Wen Zhang,Yongjie Zhou,Songjiang Huang,Jiaze Yu,Minjie Yang,Zihan Zhang,Jingqin Ma,Jianjun Luo,Shengxiang Rao,Daru Lu,Shaojun Peng,Yongbin Cao,Lingxiao Liu,Zhiping Yan
In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells . Moreover, a porous microcarrier , approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.
研究领域:
肿瘤学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 25
·67174-67186
·
IF 5.8
He Jing,Chen Sijia,Xu Yulin,Sun Mengxin,Yang Tingting,Liang Li,Xiong Xinyu
Over recent years, much attention has been paid to aging problem of microplastics and adsorption behavior of antibiotic on microplastics. In this study, four microplastics, including polystyrene (PS), polypropylene (PP), polyamide (PA) and polyethylene (PE), were photoaged by UV light in anoxic environment. The surface characteristics of microplastics and adsorption behavior of norfloxacin (NOR) on microplastics were investigated. Results indicated that the specific surface area and crystallinity increased, and hydrophobicity weakened of microplastics after UV aging. The content of C element decreased and the content of O barely changed in the aged microplastics. In addition, the adsorption of NOR on microplastics yielded a better fitness for the pseudo-second-order kinetics, Langmuir and Freundlich models. The adsorption capacities of NOR on PS, PA, PP, and PE at 288 K were 16.01, 15.12, 14.03, and 13.26 mg·g −1 , respectively, while the adsorption capacities of NOR on aged microplastics were reduced to 14.20, 14.19, 11.50, and 10.36 mg·g −1 , respectively, due to decrease of hydrophobicity and increase of crystallinity of microplastics after UV aging. The adsorption of NOR on microplastics decreased with the increase of temperature, implying the adsorption process was exothermic. Adsorption mechanism analysis showed that Van der Waals force was the main influential mechanism of the adsorption of NOR on PP and PE, and hydrogen bond was the main factor affecting the adsorption of NOR on PA, while the π-π interaction was the main mechanism impacting the adsorption of NOR on PS. Aging time and salinity significantly affect the adsorption of NOR on microplastics. With the increase of humic acid concentration and pH, the adsorption of NOR on microplastics first reduced and then rose. This study provides a basis for further clarifying the mechanism of UV aging microplastics and a reference for the study of combined pollution behavior of microplastics and antibiotics.
研究领域:
环境科学
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污染生态学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2023
·Vol. 120
·期 30
·e2302014120
·
IF 11.1
Yu Xia,Juan Li,Yuanzheng Zhang,Yongguang Yin,Bolei Chen,Yong Liang,Guibin Jiang,Richard N. Zare
Spontaneous generation of reactive oxygen species (ROS) in aqueous microdroplets or at a water vapor–silicate interface is a new source of redox chemistry. However, such generation occurs with difficulty in liquid water having a large ionic strength. We report that ROS is spontaneously produced when water vapor contacts hydrogen-bonded hydroxyl groups on a silicate surface. The evolution of hydrogen-bonded species such as hydroxyl groups was investigated by using two-dimensional, time-resolved FT-IR spectroscopy. The participation of water vapor in ROS generation is confirmed by investigating the reaction of D2O vapor and hydroxyl groups on a silicate surface. We propose a reaction pathway for ROS generation based on the change of the hydrogen-bonding network and corresponding electron transfer onto the silicate surface in the water vapor–solid contact process. Our observations suggest that ROS production from water vapor–silicate contact electrification could have contributed to oxidation during the Archean Eon before the Great Oxidation Event.
研究领域:
地球化学
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环境科学
·
氧化还原反应机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Energy
·
2025
·Vol. 10
·期 5
·630-640
·
IF 60.1
Wu Tong,Chen Shuo,Su Zhenghua,Wang Zi,Luo Ping,Zheng Zhuanghao,Luo Jingting,Ma Hongli,Zhang Xianghua,Liang Guangxing
Sulfide kesterite Cu 2 ZnSnS 4 (CZTS) is a competitive photovoltaic material, especially for multijunction solar cells. However, the device power conversion efficiency has remained stagnant for years. Deep-level defects, such as sulfur vacancies (V S ), cause serious non-radiative recombination of charge carriers. Here we propose a passivation strategy for V S through the heat treatment of the CdS/CZTS heterojunction in an oxygen-rich environment. In this process, V S are occupied by oxygen atoms, suppressing V S defects. In addition, the diffusion of Cd ions to the CZTS absorber layer, and the formation of positive Na–O and Sn–O complexes can passivate related defects. These effects led to a reduced charge recombination and favourable band alignment. We demonstrate a certified efficiency of 11.51% for air-solution-processed CZTS solar cells (bandgap of 1.5 eV) without any extrinsic cation alloying. The study offers insights into defect passivation and performance improvement mechanism of kesterite solar cells.
研究领域:
材料科学
·
太阳能电池研究
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Junzhe Fu,Weijiang Yu,Yixian Mu,Xuedan Qian,Xinyi Li,Ke Sun,Youxiang Wang,Jian Ji
Hypertrophic scars (HS) result from aberrant wound healing, often leading to disfigurement and functional impairment. Hypoxia is a prominent feature of HS; however, its impact on therapeutic efficacy remains unexplored, presenting a potential pathway for advancing HS treatments. Here, hypoxia is identified as a limiting factor in the efficacy of 5-fluorouracil (5-Fu), a widely used clinical drug for HS. At the gene expression level, 5-Fu response genes associated with the mitotic cell cycle, such as BUB1 and SPAG5, fail to be downregulated under hypoxia in human HS fibroblasts, contributing to the altered cytotoxic response. To address this limitation, an oxygen-popping microneedle (MN) system is developed to alleviate hypoxia in HS and enhance 5-Fu-based therapy. Inspired by the gas-release mechanism of Pop Rocks candy, high-pressure oxygen-trapping particles (HOTP) are formulated and integrated into a core–shell MN platform, enabling localized co-delivery of oxygen and 5-Fu. The popping release of oxygen also facilitates 5-Fu penetration into dense HS tissue. In vivo studies provide strong evidence that the MN system effectively mitigates hypoxia, significantly enhancing the therapeutic efficacy of 5-Fu. This research presents an innovative strategy for optimizing HS therapy by alleviating hypoxia, with the potential to inform future advancements in HS treatment.
研究领域:
医学
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生物材料学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF THE AMERICAN CERAMIC SOCIETY
·
2024
·Vol. 108
·期 1
·e20141
·
IF 3.5
Fang He,Yejie Cao,Yongsheng Liu,Jingxin Li,Jing Wang,Binghui Zhang,Ning Dong
SiC f /SiC composites have emerged as one of the most promising materials for aero-engine hot-end structures. However, their performance is limited by their susceptibility to oxidation and corrosion reactions with oxygen and water vapor. To overcome this challenge, antioxidant-modified phases are introduced into matrices of SiC f /SiC composites which improve their water and oxygen resistance. In this study, the resistance of SiC f /SiC composites modified by yttrium silicate matrix (SiC f /SiC-YS composites) to air at 1000–1400°C and water-oxygen environments at 1200°C was investigated. The diffusion paths of oxygen in SiC f /SiC-YS composites and the antioxidant behavior of the yttrium silicate matrix were discussed. Additionally, the differences in oxygen and water-oxygen corrosion resistance of SiC f /SiC-YS composites at the same temperature were compared. The strength retention of SiC f/ SiC-YS composites after oxidation and water-oxygen corrosion at 1200°C were 138.6% and 108.8%, respectively. This indicates that the addition of water vapor accelerated the degradation of SiC f /SiC-YS composites. By comparing with SiC f /SiC composites, it can be concluded that the modification of the yttrium silicate matrix considerably improved the oxidation resistance of SiC f /SiC composites.
研究领域:
材料科学
·
航空航天工程
✓ 已验证
产品关联
DOI
高影响因子
Surfaces and Interfaces
·
2025
·
IF 6.3
Xianjiao Tang,Xiaojing Yang,Yuhan Wang,Liping Chen,Pengwei Chen,Mei-Xia Zhao
The development of near-infrared (NIR) multifunctional phototherapy agents is important for expanding the application of photodynamic therapy (PDT)/photothermal therapy (PTT) for tumor diagnosis and treatment. Here, we constructed a phototherapeutic agent, CYPT nanoparticles (NPs), based on a cyanine dye (Cy7) for synergistic NIR image-guided tumor-specific PDT/PTT. CYPT NPs produced large amounts of type I O 2 •− and type II 1 O 2 under 808-nm laser irradiation with a high photothermal conversion efficiency (33.5%). Moreover, CYPT NPs targeted the lysosomes of cancer cells and reduced GSH, contributing to the high efficiency of PDT. CYPT NPs had similar inhibitory effects on 4T1 cells under hypoxic and normoxic conditions. Experiments in tumor-bearing mice confirmed that CYPT NPs can be enriched in tumor tissues, have good NIR fluorescence imaging performance, and exhibit efficient synergistic PDT/PTT, thus providing an attractive method for accurate tumor targeting and efficient treatment.
研究领域:
肿瘤学
·
生物医学工程
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Guijie Wei,Jianhua Chen,Ziqi Jing,Yanyi Li,Zhihui Li,Wei Zheng,Xiurui Sun,Wenwen Zhao,Zhe Zhang,Xue Wang,Hongcui Han,Chu Li,Yujie Zhang,Pengkai Ma
Mitochondria are appealing targets in cancer therapy for providing a suitable microenvironment and energy supply. Herein, we constructed a glycosylated poly(amido amine)/celastrol (PAMAM/Cel) complex for hypoxia-activated mitochondria-specific drug delivery and chemothermal therapy to inhibit tumor growth and metastasis. The complex was characterized by high photothermal conversion efficiency, hypoxia-sensitive polyethylene glycol (PEG) outer layer detachment, and alkaline-sensitive drug release. The complex showed specific cellular uptake in glucose transporter 1 (GLUT1)-overexpressing tumor cells and mitochondrial accumulation in a hypoxic environment. Combined with near-infrared (NIR) laser irradiation, the complex exhibited higher cytotoxicity, apoptosis induction, and metastasis inhibition rates due to the synergistic chemothermal effect. Similarly, the complex also targeted tumors and accumulated in mitochondria in tumor-bearing nude mice, resulting in superior inhibitory effects on tumor growth and metastasis as well as low systematic toxicity. Further mechanistic studies discovered that the complex impaired the mitochondrial membrane, reduced adenosine triphosphate (ATP) content, and regulated metastasis-related protein expression. Thus, the present study provides a promising nanomedicine for tumor therapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 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）