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Nucleolin targeting AS1411 aptamer modified pH-sensitive micelles for enhanced delivery and antitumor efficacy of paclitaxel

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Nano Research 2015年第1期8卷 201-218页

作者： Jinming Zhang Rule chen Xiefan Fang fengqian chen Yitao Wang Meiwan chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Macao 999078 China Department of Pediatrics College of Medicine University of Florida Gainesville FL 32610 USA

Targeted drug delivery coupled with rapid drug release in cytoplasm is a powerful strategy to enhance efficacy and reduce off-target effects of anti-cancer drugs. Herein, we describe a dual-functional mixed micellar system consisting of a pH-responsive copolymer D-α-tocopheryl polyethylene glycol 1000-block- poly-（β-amino ester）（TPGS-b-PBAE, TP） and AS1411 aptamer （Apt） decorated TPGS polymer （Apt-TPGS）, which recognizes the over-expressed nucleolin on the plasma membrane of cancer cells. The anti-cancer drug paclitaxel （PTX） was encapsulated in the Apt-mixed micelles, and these drug-loaded micelles had a suitable particle size and zeta potential of 116.3 nm ± 12.4 nm and -26.2 mV ±4.2 mV, respectively. PTX/Apt-mixed micelles were stable at pH 7.4, but they dissociated and quickly released the encapsulated PTX in a weakly acidic environment （pH 5.5）. Compared with non-Apt modified mixed micelles, more Apt-modified mixed micelles were internalized in SKOV3 ovarian cancer cells, whereas no significant difference in cellular uptake was observed in normal cells （LO2 cells）. The enhanced transmembrane ability of Apt-modified mixed micelles was achieved through Apt-nucleolin interaction. With a synergistic effect of cancer cell recognition and pH-sensitive drug release, we observed significantly increased cytotoxicity and G2/M phase arrest against SKOV3 cells by PTX/ Apt-mixed micelles. Intravenous administration of PTX/Apt-mixed micelles for 16 days significantly increased tumor accumulation of PTX, inhibited tumor growth, and reduced myelosuppression on tumor-bearing mice compared with free PTX injection. Therefore, this dual-functional Apt-mixed micellar system is a promising drug delivery system for targeted cancer therapy.

关键词： AS1411 aptamer pH-sensitive micelles paclitaxel ovarian cancer

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Glycyrrhetinic Acid-Decorated and Reduction-Sensitive Micelles for Enhancing Bioavailability and Anti-hepatocellular Carcinoma Efficacy of Tanshinone IIA

Glycyrrhetinic Acid-Decorated and Reduction-Sensitive Micell...

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第十四届全国中药和天然药物学术研讨会

作者： fengqian chen Jinming Zhang Meiwan chen Yitao Wang University of Macau

In the present study,we developed a dual-functional biodegradable micellar system named glycyrrhetinic acid-poly（ethylene glycol）-graft-poly（lactic-co-glycolic acid） polymers（GA-PEG-SS-PLGA） to enhancing bioavailability and anti-hepatocellular carcinoma efficacy of Tanshinone IIA（TAN MA）.These micelles was achieved by adding a GA component,which targets liver cells with overexpressed GA receptors,and a redox-sensitive disulfide linkage,which breaks in hepatocellular carcinoma（HCC） cells with elevated intracellular glutathione *** using the solvent evaporation technique,GA-PEG-SS-PLGA micelles with excellent TAN IIA loading capacity were prepared,and the drug encapsulation and loading efficiency were 83.7%and 7.6%,***,after being added to 10 mM dithiothreitol（DTT）for 24 h,the GA-PEG-SS-PLGA micelles exhibited rapid aggregation and faster drug release compared with the redox-insensitive ***,the GA-decorated micelles had high cellular uptake and excellent hepatoma-targeting ability via endocytosis after binding to GA *** and biodistribution studies revealed that TAN IIA-loaded GA-PEG-SS-PLGA micelles significantly prolonged circulation time,improved bioavailability,and increased liver accumulation of TAN *** addition,TAN IIA-loaded GA-PEG-SS-PLGA micelles exhibited enhanced cytotoxicity and pro-apoptotic effects against HepG2 cells,mediated by up-regulation of intracellular ROS level,increased cell cycle arrest at S phase,enhanced necrocytosis,and up-regulation of P38 protein *** together,GA-PEG-SS-PLGA micelles provide a novel strategy to effectively deliver TAN IIA for HCC therapy._______________________________________________________________________

关键词： Micelles Glycyrrhetinic acid Redox-sensitive Tanshinone IIA

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Design and Evaluation of pH-sensitive Micelles for Evodiamine Delivery in Cancer Therapy

Design and Evaluation of pH-sensitive Micelles for Evodiamin...

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“好医生杯”中药制剂创新与发展论坛

作者： fengqian chen Jinming Zhang Shengpeng Wang Lu Wang Meiwan chen Yitao Wang State Key Laboratory of Quality Research in Chinese Medicine(University of Macau) Institute of Chinese Medical SciencesUniversity of Macau

To deliver anticancer agents better in cancer chemotherapy,we designed amphiphilic polymers TPGS-PBAE(TBAE)as micelle carriers not only to improve poor water solubility of natural compounds,but also benefit to control drug release by acidic micro-environment trigger in tumor *** this present study,TBAE were synthesized and identified byH NMR ***,Evodiamine(EVO)was loaded in pH-sensitive TBAE nanomicelles by solvent evaporation *** characterization of these micelles was investigated by dynamic laser light scattering,transmission electron microscope,and atomicforce microscope *** entrapment efficiency and loading efficiency of EVO-TBAE micelles were 71.3±0.5%and3.52±0.03%by *** particle size,PDI and zeta potential were 82.17±0.50 nm,0.17±0.03 and-36.9±0.13 mV respectively,showing homogeneous size distribution and low *** physical status and drug release in vitro were compared in different pH *** pH 7.4,EVO-TBAE micelles was stable and showed sustained drug release in72h,while EVO-TBAE micelles showed a bigger size,unstable state and fast drug release in ***,Cytotoxicity for MCF-7 cells in different pH values from 24h to 72h was evaluated by MTT *** the enhanced cytotoxicity of nanomicelles had observed compared to free EVO drugs,the ICvalues of EVO-TBAE micelles in pH 6.4 were much lower than that inpH 7.4 at each time *** a word,these results suggest that our pH-sensitive micelles would be a potential delivery platform for anticancer compounds in cancer chemotherapy.

关键词： TPGS-PBAE micelles evodiamine PH-sensitive anticancer.

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Andrographolide Loaded PLGA-PEG-PLGA Nanoparticles for Breast Cancer Chemotherapy

Andrographolide Loaded PLGA-PEG-PLGA Nanoparticles for Breas...

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“好医生杯”中药制剂创新与发展论坛

作者： Jinming Zhang Shengpeng Wang fengqian chen Lu Wang Meiwan chen Yitao Wang State Key Laboratory of Quality Research in Chinese Medicine(University of Macau) Institute of Chinese Medical SciencesUniversity of Macau

Andrographolide(ADG),a main component in herb Andrographis paniculata,has been identified as one of the most promising anti-tumor ***,high hydrophobicity greatlyrestricts its efficacy and application in cancer *** the present study,PLGA-PEG-PLGA amphipathic copolymers were synthesized by gentle chemical grafting methods to formulate nanoparticles(NPs)for ADG *** NPs with a high encapsulation and loading efficiency about 92%and 9%were obtained by *** as inerratic nanospheres in nano solution,the average size,zeta potential and critical micelle concentration of ADG NPs were about 124nm,-13mV and 1.98×10g/mL,*** comparison to free ADG,ADG NPs exhibita sustained drug release profilein *** importantly,the enhanced cytotoxic effectsof ADG NPson breast cancer MAD-MB-231 cells were revealed in vitro,after co-incubation with drugs for *** stronger cell cycle arrest effects at G1 phase and pro-apoptosis effectswere observed in the correspondingconcentration of ADG(15μM)to investigateits potential *** is also shown that the internalization of NPs could be observed in cytoplasm by laser confocal *** quantitative results of in vitro cellular uptake showed that after co-incubation for4h,theinternalization amounts of NPs would significantly more about 2.3 times than that of free agents,which would contribute to its enhanced *** a word,these results demonstrated ADG encapsulated in PLGA-PEG-PLGANPs may be a new drug delivery strategy for improving efficacy in cancer therapy.

关键词： nanoparticles andrographolide anticancer PLGA-PEG-PLGA copolymer

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Preparation of Evodiamine-loaded PH-sensitive TBAE Micelles and Studies on Anticancer

Preparation of Evodiamine-loaded PH-sensitive TBAE Micelles ...

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“好医生杯”中药制剂创新与发展论坛

Evodiamine(EVO),a kind of traditional Chinese medicine monomer which has good anti-cancer *** synthesised an amphiphilic polymer TBAE to improve poor water solubility which also can respond acidic environment in tumor *** the present study,EVO loaded PH-sensitive TBAE micelles were prepared by solvent evaporation *** usedHNMR to analysis polymer TBAE and characterisation of the micelles was investigated by dynamic laser light scattering,transmission electron microscope and atomicforce *** entrapment efficiency and loading efficiency of EVO-TBAE micelles were 71.3±0.5%and 3.52±0.03%by *** particle size,PDI and zeta potential of EVO-TBAE micelles were 82.17±0.50nm,0.17±0.03 and-36.9±0.13mV,micelles has a monomodal nanoparticle size distribution and low *** of micelles and change of micelle sizes in different PH were measured,*** PH=7.4,EVO-TBAE micelles was stable and sustained release in 72h;In PH=6.4,size of EVO-TBAE micelles was changeable and fast *** was evaluated by MTT assay in MCF-7 *** study showed that the IC50 values of EVO-TBAE micelles in PH=6.4 were much lower than that of PH=7.4 at each time ***,these results suggest that PH-sensitive micelles can be used as a potential delivery formulation for Evodiamine to enhance anticancer activity.

关键词： micelles evodiamine PH-sensitive anticancer

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中药合天保康注射液治疗椎—基底动脉供血不足性眩晕74例

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浙江中医药大学学报 2006年第6期30卷 633-634页

作者：陈丰钱浙江省诸暨市马剑镇医院诸暨311803

[目的]探讨中药伍用天保康注射液治疗椎—基底动脉供血不足性眩晕的疗效。[方法]对椎基底动脉供血不足性眩晕74例,以益气、活血、通络作用的方药伍用静滴天保康注射液治疗。[结果]中药伍用天保康注射液治疗,总有效率达93·24%。[结论]... 详细信息

[目的]探讨中药伍用天保康注射液治疗椎—基底动脉供血不足性眩晕的疗效。[方法]对椎基底动脉供血不足性眩晕74例,以益气、活血、通络作用的方药伍用静滴天保康注射液治疗。[结果]中药伍用天保康注射液治疗,总有效率达93·24%。[结论]中药伍用天保康注射液治疗椎—基底动脉供血不足性眩晕是一疗效显著的方法。

关键词：眩晕天保康注射液椎基底动脉供血不足中医药治疗

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Profile of *** chen

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Science China(Life Sciences) 2024年第10期67卷 2062-2063页

作者： chen, Songlin Yellow Sea Fisheries Res Inst Qingdao Peoples R China

For decades,*** has been engaged in fish germplasm preservation,sex control and research focusing on molecular breeding for disease *** discovered the first sex-specific molecular marker of fish(chen et al.,2007),deciphered the first fish genome(Chinese tongue sole)in China,revealed the sex determination mechanism in fish(chen et al.,2014),and created molecular sex control *** also discovered the molecular mechanism of metamorphosis in flatfish(Shao et al.,2017)and developed China's first fish disease-resistant breeding gene chip,“YUXIN No.1”.

关键词： technology breeding

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Effect of Reclamation on the Groundwater-Lake Water Interaction in chen Lake

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Journal of Earth Science 2024年第3期35卷 1083-1086页

作者： Kun Lei Teng Ma Liuzhu chen Zhenxing Li Yu chen School of Environmental Studies State Key Laboratory of Biogeology and Environmental GeologyChina University of GeosciencesWuhan 430078China

0 INTRODUCTION To relieve the short supply of suitable land for residing,cultivating,and commerce,it is accepted to reclaim land from lakes,river estuaries,and coastal regions in many countries(Mancini et al.,2020).The large-scale reclamation activities have an irreversible effect on the mico-geomorphology and hydrodynamic system of seasonally flooded areas(Zhang et al.,2019;Yu et al.,2018).For example,coastal regions reclaimed extended the groundwater flow paths,as well as created groundwater level rise,resulting in water-logging in the reclaimed area(Hu et al.,2008).Similar changes in groundwater flow systems may alter groundwater-lake water interactions,and it can ultimately affect the water cycle in the lake ***,such detailed studies are presently *** addition,natural exchanges between the lake and groundwater systems can be strongly affected by physical hydrological processes(Javadzadeh et al.,2020),chemical properties(Kamtchueng et al.,2015),and bioto behavior(Hancock et al.,2005).

关键词： groundwater coastal logging

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Meridional deflection of global eddy propagation derived from tandem altimetry: Mechanism and implication

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Science China Earth Sciences 2024年第3期67卷 811-825页

作者： Ge chen Xiaoyan chen Frontiers Science Center for Deep Ocean Multispheres and Earth System School of Marine TechnologyOcean University of ChinaQindao 266100China Laboratory for Regional Oceanography and Numerical Modeling Laoshan LaboratoryQindao 266237China

A common view on meridional deflection of eddy propagation is poleward for cyclones and equatorward for anticyclones. This widely accepted polarity-sensitive pattern has been increasingly undermined given that it is systematically violated on both zonal and regional scales as recently reported. Here, we approach the problem by exploring these violations in terms of eddy effects of spatiotemporal geostrophy, thermal fading, and flow dragging, yielding the following main conclusions.(1) The polarity-dependent deflection discrepancy is a pseudo feature resulting from a biased fit to the normalized eddy tracks which are spatially asymmetric(though azimuthally symmetric) between the two signs;Instead, the primary pattern of eddy deflection appears to be geographically correlated and polarity independent.(2) Geostrophic adjustment plays a critical role in defining the meridional movement of an eddy. Specifically, a consistent poleward(equatorward) trajectory bending of spatially(temporally) ageostrophic eddies is observed irrespective of their polarity.(3) The mechanism of eddy deflection is also determined by its zonal propagation direction. Westward propagating eddies are substantially affected by thermal fading, while opposite ones by flow dragging. A realistic and comprehensive understanding of eddy deflection mechanisms serves as a significant contribution to the prediction of eddy trajectory, and the protection of ocean environment.

关键词： Mesoscale eddies Eddy propagation Eddy meridional deflection Satellite observation Geostrophic adjustment

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A refined representation method of the particle size distribution curve based on grading entropy

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Particuology 2024年第5期88卷 302-311页

作者： Xing Li Qun chen Zhaozhao Liu cheng Zhou chen Wang chen chen State Key Laboratory of Hydraulics and Mountain River Engineering College of Water Resource and HydropowerSichuan UniversityChengdu610065China

The particle size distribution(PSD)curve is an important expression of the basic properties of the *** characteristic parameters such as median particle size D_(50),effective particle size D_(10),and some combinations of characteristic parameters can only represent some points of the PSD curve,failing to represent all information of the PSD *** this paper,a fraction characteristic parameter F that could reflect the fraction size variation of the PSD curve was introduced based on grading *** a new presentation method of the A-B-F three parameters was proposed for a refined representation of the PSD *** was found that the newly constructed model not only better represents the differences in the width of PSD curves but also has a higher sensitivity than the A-B two-parameter model proposed by Lő*** PSD curves with similar distributions,the new presentation method has a higher degree of discrimination than that of the D_(50)-C_(u)-C_(c) three-parameter or the four-parameter combination G_(c) proposed by ***,the application of this new method in describing the spatial nonuniformity distribution of depositions and predicting the soil hydraulic conductivity was *** research results can provide a reference for the refined representation of PSD curves.

关键词： Grading entropy Particle size distribution curve Refined representation

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