Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains unsatisfactory.Here,we aimed to identify promising targeted agents that synergize wi...Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains unsatisfactory.Here,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in TNBC.By using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive TNBC.The combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,respectively.Furthermore,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and MK-8776.This HA-modified nanosystem managed targeted activation via pH/glutathione responsiveness.HMnE&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a carrier.Collectively,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.展开更多
目的:构建基于聚乳酸—羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量...目的:构建基于聚乳酸—羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量聚合物分散性指数、Zeta电位、纳米粒径和载药率,进行纳米粒表征;以荧光标记法观察心肌细胞对纳米粒子的摄取情况。体外建立心肌细胞缺氧模型,体内建立小鼠急性心肌缺血损伤模型,检测不同浓度E-P-NPs对细胞活力、细胞凋亡、心肌肌钙蛋白I(cTn-I)水平及Bcl-2、Caspase9、Bax表达的影响。结果:E-P-NPs呈圆球形,多分散性指数(PDI)为0.285,平均粒径193.5 nm,电位-28.7 m V,载药率9.23%,可被心肌细胞摄取。体内、外实验研究均表明,E-P-NPs可剂量依赖性地增强心肌细胞活力,降低c Tn-I水平,降低凋亡率,上调Bcl-2蛋白表达,下调Caspase9、Bax蛋白表达,抑制细胞凋亡;E-P-NPs对缺血心肌的保护作用优于EGCG。结论:E-P-NPs粒径分布较集中,均一性较好,可通过抑制凋亡减轻心肌缺血损伤,且能使EGCG更好地发挥药效。展开更多
Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or in...Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.展开更多
基金supported by the Key INTERNATIONAL COOPERATION of the National Natural Science Foundation of China(No.81920108029,China)the Key Foundation for Social Development Project of the Jiangsu Province,China(No.BE2021741,China).
文摘Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains unsatisfactory.Here,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in TNBC.By using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive TNBC.The combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,respectively.Furthermore,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and MK-8776.This HA-modified nanosystem managed targeted activation via pH/glutathione responsiveness.HMnE&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a carrier.Collectively,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.
文摘目的:构建基于聚乳酸—羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量聚合物分散性指数、Zeta电位、纳米粒径和载药率,进行纳米粒表征;以荧光标记法观察心肌细胞对纳米粒子的摄取情况。体外建立心肌细胞缺氧模型,体内建立小鼠急性心肌缺血损伤模型,检测不同浓度E-P-NPs对细胞活力、细胞凋亡、心肌肌钙蛋白I(cTn-I)水平及Bcl-2、Caspase9、Bax表达的影响。结果:E-P-NPs呈圆球形,多分散性指数(PDI)为0.285,平均粒径193.5 nm,电位-28.7 m V,载药率9.23%,可被心肌细胞摄取。体内、外实验研究均表明,E-P-NPs可剂量依赖性地增强心肌细胞活力,降低c Tn-I水平,降低凋亡率,上调Bcl-2蛋白表达,下调Caspase9、Bax蛋白表达,抑制细胞凋亡;E-P-NPs对缺血心肌的保护作用优于EGCG。结论:E-P-NPs粒径分布较集中,均一性较好,可通过抑制凋亡减轻心肌缺血损伤,且能使EGCG更好地发挥药效。
基金supported by the National Natural Science Foundation of China(Grant No.51677146)Project of Independent Innovative Experiment for Postgraduates in Medicine in Xi’an Jiaotong University(Grant No.JSCX-2018-014)the Special Scientific Research Project Funds of Shaanxi Province(Grant No.18JK1102).
文摘Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.
