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Tumor acid microenvironment-activated self-targeting&splitting gold nanoassembly for tumor chemo-radiotherapy

Bioactive Materials 2022年第1期7卷 377-388页

作者： Xiaomin Li Licheng Yu chuangnian zhang Xiaoyan Niu Mengjie Sun Zichao Yan Wei Wang Zhi Yuan Key Laboratory of Functional Polymer Materials of Ministry of Education College of ChemistryNankai UniversityTianjin300071China Tianjin Key Laboratory of Biomaterial Research Biomedical Barriers Research CenterInstitute of Biomedical EngineeringChinese Academy of Medical Science&Peking Union Medical CollegeTianjin300192China Collaborative Innovation Center of Chemical Science and Engineering Nankai UniversityTianjin300071China

Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic ***,a pH-responsive gold nanoassembly is designed to overcome these *** glycol linked raltitrexed(RTX,target ligand and chemotherapy drug)and two tertiary amine molecules(1-(2-aminoethyl)pyrrolidine and N,N-dibutylethylenediamine)are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX).The Au-NNP(RTX)nanoassembly could remain at about 160 nm at the blood circulation(pH 7.4),while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH(pH 6.8).This pH-responsive disassembly behavior endows Au-NNP(RTX)better tumor tissue permeability through the better diffusion brought by the size ***,after disassembly,more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake *** importantly,the results show that Au-NNP(RTX)possesses of high tumor accumulation and effective tumor penetration,thereby enhancing the tumor chemo-radiotherapy efficiency.

关键词： Gold nanoassembly Disassemble Penetration Self-target Chemo-radiotherapy

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Glycyrrhetinic acid-modified nanoparticles for drug delivery: Preparation and characterization

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Chinese Science Bulletin 2009年第10期54卷 3121-3126页

作者： TIAN Qin WANG Wei HE XiaoTing ZHU XiaoCui HUANG Wei zhang chuangnian YUAN Zhi CHEN XueSi Key Laboratory of Functional Polymer Materials Ministry of Education Institute of Polymer Chemistry Nankai University Tianjin 300071 China State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of SciencesChangchun 130022 China

In this work, glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) used as liver targeted carrier for drug delivery, was prepared via hemisuccinate as a bridged group. The structure of the product was confirmed by IR and NMR methods and the degree of substitution (DS) of glycyrrhetinic acid groups was estimated via elemental analysis. Nanoparticles were formed by ionic gelation methold. The drug-loading and release behavior of the nanoparticles were investigated using BSA as the model drug. The results indicated that the carrier with a highest DS of 5.19% could be got and the DS was controlled by changing reaction temperature or feed ratio. BSA could be entrapped into the nanoparticles with the drug-loading ratio of 26.3% and the encapsulation efficiency of 81.5%. A sustained release over an 11-day period was observed in pH 7.4 in vitro.

关键词：药物输送纳米粒子甘草次酸酸改性表征制备核磁共振方法牛血清白蛋白

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Titanium alloy composited with dual-cytokine releasing polysaccharide hydrogel to enhance osseointegration via osteogenic and macrophage polarization signaling pathways

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Regenerative Biomaterials 2022年第1期9卷 372-388页

作者： Yaping Wang Zujian Feng Xiang Liu Chunfang Yang Rui Gao Wenshuai Liu Wenbin Ou-Yang Anjie Dong chuangnian zhang Pingsheng Huang Weiwei Wang Department of Polymer Science and Engineering Key Laboratory of Systems Bioengineering(Ministry of Education)School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China Key Laboratory of Innovative Cardiovascular Devices Chinese Academy of Medical SciencesBeijing 100037China Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China Structural Heart Disease Center National Center for Cardiovascular DiseaseChina and Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Titanium alloy has been widely used in orthopedic surgeries as bone defect ***,the regeneration of high-quality new bones is limited due to the pro-inflammatory microenvironment around implants,resulting in a high occurrence rate of implant loosening or failure in osteological *** this study,extracellular matrix-mimetic polysaccharide hydrogel co-delivering BMP-2 and interleukin(IL)-4 was composited with 3D printed titanium alloy to promote the osseointegration and regulate macrophage response to create a pro-healing microenvironment in bone ***,it is discovered from the bioinformatics data that IL-4 and BMP-2 could affect each other through multiple signal pathways to achieve a synergistic effect toward *** composite scaffold significantly promoted the osteoblast differentiation and proliferation of human bone marrow mesenchyme stem cells(hBMSCs).The repair of large-scale femur defect in rat indicated that the dual-cytokinedelivered composite scaffold could manipulate a lower inflammatory level in situ by polarizing macrophages to M2 phenotype,resulting in superior efficacy of mature new bone regeneration over the treatment of native titanium alloy or that with an individual ***,this work highlights the importance of M2-type macrophages-enriched immune-environment in bone *** biomimetic hydrogel–metal implant composite is a versatile and advanced scaffold for accelerating in vivo bone regeneration,holding great promise in treating orthopedic diseases.

关键词： hydrogel composite scaffold bone regeneration cytokine delivery macrophage polarization

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甘草次酸修饰海藻酸钠纳米给药系统的肝靶向性评估

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高分子学报 2011年第8期21卷 817-823页

作者：张闯年王平赖全勇张倩张玥吴玉昆刘通王蔚袁直南开大学高分子化学研究所功能高分子材料教育部重点实验室天津300071 苏州大学材料与化学化工学部苏州215123

通过EDC/NHS偶联反应将疏水性肝靶向小分子甘草次酸(GA)连接到天然多糖海藻酸钠(ALG)上,制备了具有双亲性肝靶向药物载体材料(GA-ALG).采用乳化法对广谱抗癌药物阿霉素(DOX)进行包载,得到肝靶向载药纳米粒子(DOX/GA-ALG NPs).利用单光... 详细信息

通过EDC/NHS偶联反应将疏水性肝靶向小分子甘草次酸(GA)连接到天然多糖海藻酸钠(ALG)上,制备了具有双亲性肝靶向药物载体材料(GA-ALG).采用乳化法对广谱抗癌药物阿霉素(DOX)进行包载,得到肝靶向载药纳米粒子(DOX/GA-ALG NPs).利用单光子发射型计算机断层成像技术(SPECT)和药物体内分布实验对DOX/GA-ALG NPs的肝靶向性进行了评估.SPECT成像显示,99mTc标记空白纳米粒子(99mTc-GA-ALG NPs)主要集中在Wistar大鼠的肝脏部位,富集率达40.2%.药物体内组织分布结果显示,尾静脉注射3 h后,DOX/GA-ALG NPs组小鼠肝脏中阿霉素浓度达到67.7μg/g,是***组的4.7倍.相对摄取率(re)、靶向效率(te)和加权平均靶向效率(te*)数据同样表明DOX/GA-ALG NPs具有显著肝靶向能力.研究表明甘草次酸修饰海藻酸钠纳米给药系统具有良好的肝靶向性.

关键词：甘草次酸海藻酸盐纳米给药系统靶向效率

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新型完全生物可吸收封堵器经导管封堵膜周部室间隔缺损:一项多中心前瞻性随机对照研究

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Science Bulletin 2023年第10期68卷 1051-1059,M0004页

作者：王首正李泽夫王云兵赵天力莫绪明范太兵李建华尤涛邓润迪欧阳文斌王伟伟张闯年 Gianfranco Butera Ziyad MHijazi 逄坤静朱达蒋世良张戈军胡晓鹏谢涌泉张凤文房芳孙静平李萍陈娟骆志玲潘湘斌 Department of Structural Heart Disease Fuwai Hospital&National Center for Cardiovascular DiseaseKey Laboratory of Innovative Cardiovascular DevicesChinese Academy of Medical Sciences&Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing 100037China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China Department of Cardiovascular Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China Department of Cardiovascular Surgery Children’s Hospital of Nanjing Medical UniversityNanjing 210008China Department of Cardiovascular Surgery Fuwai Central China Cardiovascular HospitalZhengzhou 451464China Department of Cardiovascular Surgery The Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiovascular Surgery Gansu Province HospitalLanzhou 730000China Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Science&Peking Union Medical CollegeTianjin 300192China Department of Pediatric and Adult Congenital Heart Disease Evelina London Children’s HospitalGuy’s and St Thomas’NHS Foundation TrustLondon SE19RTUK Department of Pediatrics Sidra Heart CenterSidra Medical&Research CenterDoha 999043Qatar Department of Echocardiography Fuwai Hospital&National Center for Cardiovascular DiseaseChinese Academy of Medical Sciences&Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing 100037China Department of Structural Heart Disease Fuwai Yunnan Cardiovascular HospitalKunming 650102China Cardiology Department The Clinic Cleveland FoundationCleveland 44195USA Cardiology Department Fuwai Hospital&National Center for Cardiovascular DiseaseChinese Academy of Medical Sciences&Peking Union Medical College

生物可吸收封堵器的应用有望降低传统金属封堵器并发症的风险.之前研制的生物可吸收封堵器存在不完全降解的局限性并导致新的并发症,因此目前尚未有相关产品获批上市.本研究使用了一种新型完全可吸收封堵器,旨在探索完全可吸收封堵器治... 详细信息

生物可吸收封堵器的应用有望降低传统金属封堵器并发症的风险.之前研制的生物可吸收封堵器存在不完全降解的局限性并导致新的并发症,因此目前尚未有相关产品获批上市.本研究使用了一种新型完全可吸收封堵器,旨在探索完全可吸收封堵器治疗室间隔缺损的疗效和安全性.从2019年4月到2020年1月,本研究在七个医学中心入组125名膜周部室间隔缺损患者,经筛查后108名患者被纳入研究并随机分为植入生物可吸收封堵器实验组和金属封堵器组.所有受试者均成功植入封堵器并完成24个月的随访.生物可吸收封堵器组患者经胸超声心动图显示高亮回声在24个月内逐渐消失,说明可吸收封堵器在体内实现完全降解.对比金属封堵器,实验组器械相关心律失常发生率(5.56%vs.14.81%,P=0.112)和持续传导阻滞发生率(0/54 vs.6/54,P=0.036)显著降低.本研究提示新型完全可吸收封堵器可以在单纯超声引导下实现成功植入,同时降低术后永久性心律失常的发生率.

关键词： Ventricular septal defect Transcatheter closure Bioabsorbable Degradation Echocardiography

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