Frontiers in Pharmacology
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2021
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IF 5.811
Miao Jiefei,Meng Chi,Wu Hongmei,Shan Wenpei,Wang Haoran,Ling Changchun,Zhang Jinlin,Yang Tao
A novel hybrid CHC was designed and synthesized by conjugating β-carboline with an important active fragment N-hydroxyacrylamide of histone deacetylase (HDAC) inhibitor by an amide linkage to enhance antitumor efficacy/potency or even block drug resistance. CHC displayed high antiproliferative effects against drug-sensitive SUMM-7721, Bel7402, Huh7, and HCT116 cells and drug-resistant Bel7402/5FU cells with IC50 values ranging from 1.84 to 3.27 μM, which were two-to four-fold lower than those of FDA-approved HDAC inhibitor SAHA. However, CHC had relatively weak effect on non-tumor hepatic LO2 cells. Furthermore, CHC exhibited selective HDAC1/6 inhibitory effects and simultaneously augmented the acetylated histone H3/H4 and α-tubulin, which may make a great contribution to their antiproliferative effects. In addition, CHC also electrostatically interacted with CT-DNA, exerted remarkable cellular apoptosis by regulating the expression of apoptosis-related proteins and DNA damage proteins in Bel7402/5FU cells, and significantly accumulated cancer cells at the G2/M phase of the cell cycle by suppressing CDK1 and cyclin B protein with greater potency than SAHA-treated groups. Finally, CHC displayed strong inhibitory potency to drug-resistant hepatic tumors in mice. Our designed and synthetic hybrid CHC could be further developed as a significant and selective anticancer agent to potentially treat drug-resistant hepatocellular carcinoma.
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CATALYSIS LETTERS
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2022
·Vol. 152
·期 12
·3795-3806
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IF 2.936
Tao Wanyi,Bo Longli,Li Mingxin,Liu Jiadong
The modification of cordierite honeycomb (CH) carrier is conducive to improve the catalytic activity of catalyst that applying in the treatment of real VOCs waste gas. A honeycombed calcium aluminum silicate hydrate (C–A–S–H) thin layer was self-assembled successfully by alkaline corrosion with supersaturated Ca(OH) 2 and contacted robustly onto the CH surface (named as CHC) by chemical bond. CuMnCeO x /CHC catalyst was prepared and applied in microwave catalytic combustion of toluene to check the catalytic activity in this work. Compared with CuMnCeO x /CH catalyst, CuMnCeO x /CHC catalyst exhibited a higher catalytic capacity and the removal rate of toluene reached 99%, which was higher than 75% of CuMnCeO x /CH catalyst under same reaction conditions of toluene initial concentration 1000 mg m −3 , air flow 0.12 m 3 h −1 and bed temperature 200 °C. Based on SEM, BET, XRD, XPS, UV-Raman, H 2 -TPR and NH 3 -TPD characterizations, it showed clearly that honeycombed C–A–S–H thin layer made CuMnCeO x active particles with smaller size more uniformly embedded into the pores of itself to hinder effectively the agglomeration of active particles in reaction. The valence reversible conversion of Cu + /Cu 2+ , Mn 2+ /Mn 3+ /Mn 4+ and Ce 3+ /Ce 4+ and total valence increase of CuMnCeO x produced abundant oxygen vacancies on the catalyst surface and simultaneously improved the transformation of surface adsorbed oxygen (O ads ) to lattice oxygen (O latt ). Toluene was oxidized completely by O ads and O latt species onto the active sites and “hot spots” under microwave irradiation that following both L–H mechanism and MvK mechanism. The research work lays down a theoretical basis for the preparation of highly effective catalyst and further application in the treatment of industrial VOCs waste gas. Graphical Abstract
研究领域:
环境科学
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催化材料
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产品关联
DOI
高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Yajing Chi,Chaoqi Song,Qian Jia,Ruili Zhang,Fang Sun,Zheng Li,Yuanyuan Jia,Xian An,Zhongliang Wang,Jianxiong Li
Background: Chemodynamic therapy (CDT) has become increasingly important as a tumor treatment strategy, which relies on intracellular acid and hydrogen peroxide to kill tumor cells by generating hydroxyl radicals (·OH) through Fenton/Fenton-like reactions. However, the weakly alkaline intracellular environment considerably caused by the efflux of lactate and H + from glioblastoma cells is not conducive to CDT performance. Intracellular acidification induced by inhibiting the transmembrane monocarboxylate transporter 4 (MCT4) can enhance the therapeutic efficacy of CDT. Existing approaches suffer from insufficient MCT4 inhibition, involve complex drug synthesis, and have many unsatisfactory side effects. Methods: In this study, we constructed an anti-tumor nanoparticle formed by self-assembly driven by the coordination interaction of Fe 3+ and α-cyano-4-hydroxycinnamate (CHC) to avoid safety issues posed by excessive modification. Fe-CHC nanoparticles were designed to decrease intracellular pH through inhibition of MCT4, which transports lactate/H + to the extracellular space. The resulting intracellular accumulation of lactate and H + led to fatal acidosis and promoted ·OH generated by Fenton/Fenton-like reactions with the presence of the Fe 3+ , thus enhancing CDT-induced tumor cell death. Results: In vitro and in vivo results revealed that Fe-CHC exerted a significant synergistic anti-tumor effect by re-establishing acidosis and enhancing CDT in glioblastoma. Furthermore, the decreased H + outside the cells caused by the inhibition of lactate/H + efflux hindered extracellular matrix degradation, thereby inhibiting tumor metastasis. Conclusion: Fe-CHC is an effective anti-cancer agent against glioblastoma. This study provides valuable insights for developing acid-modulating anti-tumor nanoparticles, as well as enriching and optimizing the application of CDT in tumor therapy. Statement of Significance Our study pioneers the Fe-CHC nanoparticle, a metal-coordination polymer that targets MCT4 in glioblastoma cells to restore intracellular acidity and synergize with Fe 3+ to boost chemodynamic therapy (CDT). Unlike other studies, Fe 3+ and CHC work together to maximize the therapeutic potential and safety of Fe-CHC with minimal complexity. This innovative approach not only increased the production of reactive oxygen species within tumor cells, but also hindered tumor metastasis. Our work has important scientific implications for tumor microenvironment regulation and the application of CDT, and will provide a promising pathway for the treatment of aggressive cancers and attract a wide audience through its scientific implications.
研究领域:
肿瘤学
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纳米医学
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生物化学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2020
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IF 7.182
Juanjuan Fu,Yinglian Zhu,Fansheng Cheng,Shuangling Zhang,Tiantian Xiu,Yue Hu,Shuo Yang
For preparing stable water-in-oil-in-water emulsion, the role of nanoparticles in stabilizing the interface is very important. In this study, chitosan hydrochloride-carboxymethyl chitosan (CHC-CMC) nanoparticles were prepared considering electrostatic interactions; then the emulsion was prepared and the stability characteristics in presence of NaCl (0–200 mmol/L) and 30 d storage were studied. CHC-CMC nanoparticles (261 nm) were obtained when the CHC: CMC ratio was 1:2. CHC-CMC formation was verified by FT-IR when a new peak appeared at 1580 cm −1 ; W 2 contained 2 wt % CHC-CMC and W 1 contained 1 wt % sodium alginate , the creaming index (81.6 %) was higher for the emulsions than Tween 80 (67.4 %) after 30 d. Confocal laser scanning microscopy confirmed the double microstructures, in contrast to the collapse with Tween 80, because the CHC-CMC nanoparticles were densely adsorbing on the oil-water interface. This indicates that CHC-CMC has a stronger ability to stabilize W 1 /O/W 2 emulsion than Tween 80.
研究领域:
材料科学
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胶体与表面化学
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纳米技术
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食品科学
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DOI
高影响因子
危险品化学品经营许可证（带存储）