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Molecular engineering of dendrimer nanovectors for siRNA delivery and gene silencing

Frontiers of Chemical Science and Engineering 2017年第4期11卷 663-675页

作者： Cao, Yu Peng, Ling liu, xiaoxuan Aix Marseille Univ CNRS Ctr Interdisciplinaire Nanosci Marseille UMR 7325Equipe Labellisee Ligue Caner F-13288 Marseille France China Pharmaceut Univ State Key Lab Nat Med Ctr Drug Discovery Ctr Adv Pharmaceut & Biomat Nanjing 210009 Peoples R China China Pharmaceut Univ Jiangsu Key Lab Drug Discovery Metab Dis Ctr Drug Discovery Ctr Adv Pharmaceut & Biomat Nanjing 210009 Peoples R China

Small interfering RNA （siRNA） therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with cova- lent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types in vitro and in vivo, including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired struc^rally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self- assembling amphiphilic dendrimers to construct supramo- lecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great pro- mise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.

关键词： gene therapy RNAi therapeutics dendrimer,nanovectors gene silencing

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GRB 210323A:Signature of Long-lasting Lifetime of Supra-massive Magnetar as the Central Engine from the Merger of Binary Neutron Star

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Research in Astronomy and Astrophysics 2024年第8期24卷 32-41页

作者： Yingze Shan xiaoxuan liu Xing Yang Haoyu Yuan Houjun Lü Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China Department of Astronomy School of PhysicsHuazhong University of Science and TechnologyWuhan 430074China

Theoretically,a supra-massive neutron star or magnetar may be formed after the merger of binary neutron ***210323A is a short-duration gamma-ray burst(GRB)with a duration of lasting~1 *** light curve of the prompt emission of GRB 210323A shows a signal-peaked structure and a cutoff power-law model can adequately fit the spectra with E_p=1826±*** interestingly,it has an extremely long-lasting plateau emission in the X-ray afterglow with a duration of~10^(4)s,and then follows a rapid decay with a decay slope~*** temporal feature is challenging by invoking the external shock *** this paper,we suggest that the observed long-lasting X-ray plateau emission is caused by the energy injection of dipole radiation from supra-massive magnetar,and the abrupt decay following the longlasting X-ray plateau emission is explained by supra-massive magnetar collapsing into a black *** is the short GRB(SGRB)with the longest X-ray internal plateau emission powered by a supra-massive neutron *** this is the case,one can estimate the physical parameters of a supra-massive magnetar,and compare with other *** also discuss the possible gravitational-wave emission,which is powered by a supra-massive magnetar and its detectability,and the possible kilonova emission,which is powered by r-process and magnetar spin-down to compare with the observed data.

关键词： (stars)gamma-ray burst general-(stars)gamma-ray burst individual(GRB 210323A)-stars magnetars

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Lipase-activated glycopeptide nano-assemblies as an antibiotic nano-adjuvant to inhibit Pseudomonas aeruginosa biofilm and enhance antibacterial activity

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Science China Chemistry 2022年第12期65卷 2538-2547页

作者： Yifei Song Jingkai Zhang Yue Fei Zhangjian Huang xiaoxuan liu Li-Li Li CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology(NCNST)Beijing100190China College of Life Science and Technology Beijing University of Chemical TechnologyBeijing100029China State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug DiscoveryCenter of Advanced Pharmaceutics and BiomaterialsChina Pharmaceutical UniversityNanjing210009China

Bacterial infections,especially those caused by biofilms,pose a serious threat to public *** this work,we propose a glycopeptide-based antibiotic nano-adjuvant(GalAc-2) that can synergistically enhance the antibacterial activity of antibiotics through its biofilm inhibition *** glycopeptide nanoparticles can be specifically activated by bacterial infection overexpressed lipase and sequentially enlarged by glycosyl exposure on the *** stability and bonding affinity of the nanoparticles were enhanced through the increase in β-sheet *** bacterial growth inhibition rate of the mixture of levofloxacin(LEV) and GalAc-2 at 0.54 μg/m L was over sevenfold higher than that of LEV alone because of the electrostatic and multivalence Lec A interactions that inhibited biofilm formation on the bacterial ***,the mixture of the antibiotic with GalAc-2 significantly inhibited the abscess exposed to skin infection and significantly reduced the infiltration of immune *** believe that GalAc-2 can be further used to enhance broad-spectrum antibiotic sensitization and prolong the lifetime of antibiotics.

关键词： glycopeptide self-assembly antibiotic nano-adjuvant bacteria biofilm

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Targeted nanoparticles for precise cancer therapy

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Science China(Life Sciences) 2019年第10期62卷 1392-1395页

作者： Jinjin Wang Yongchao Wang Ruifang Wang Shouwen Zhang xiaoxuan liu Xing-Jie Liang CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Chinese Academy of SciencesNational Center for Nanoscience and Technology of ChinaBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Advanced Pharmaceutics and BiomaterialsCenter of Drug DiscoveryInstitute of Pharmaceutical SciencesChina Pharmaceutical University Nanjing 210009China Epilepsy Department Beijing Chaoyang Emergency Medical CenterBeijing 100122China

Cancer has become one of the biggest challenges in the development of modern medical science. In particular, many problems, such as low efficiency, severe side effects, metastasis, and tumor invasion, challenge the development of precise cancer therapy. Continuous advancements in medicine, however, have allowed clear differentiation between tumors and normal tissues that can be exploited for cancer therapeutics. Unlike normal cells, tumor cells have an uncontrollable growth and are infinitely proliferative. These physical, chemical, and biological differences (e.g., metabolic states, high cell density, ability to grow in hypoxic and low pH conditions, and expression of different specific receptors/ ligands) may provide a new perspective for the development of cancer therapeutics. Traditional antitumor drugs have disadvantages, such as poor solubility, insufficient bioavailability in the body, numerous side effects, and development of chemoresistance, all of which greatly limit their therapeutic efficacy.

关键词： medical science cell density

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Amphiphilic Dendrimer Vectors for RNA Delivery:State-of-the-Art and Future

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Accounts of Materials Research 2022年第5期3卷 484-497页

作者： Jiaxuan Chen Dandan Zhu xiaoxuan liu Ling Peng Aix Marseille Université CNRSCenter Interdisciplinaire de Nanoscience de MarseilleCINaM UMR 7325“Equipe Labellisée Ligue Contre le Cancer”13288 MarseilleFrance State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug DiscoveryCenter of Advanced Pharmaceuticals and BiomaterialsChina Pharmaceutical University210009 NanjingP.R.China

Dendrimers,a special family of polymers,are particularly promising materials for various biomedical applications by virtue of their well-defined dendritic structure and cooperative ***,in this Account,we present state-of-the-art amphiphilic dendrimers for nucleic acid *** acid(RNA)molecules are fast becoming an important drug modality,particularly since the recent success of mRNA vaccines against ***,RNA therapeutics offer the unique opportunity to treat diseases at the gene level and address“undruggable”***,RNA therapeutics are not stable and have poor bioavailability,imposing the need for their protection and safe delivery by vectors to the sites-of-action to allow the desired therapeutic ***,the two most advanced nonviral vectors are based on lipids and polymers,with lipid vectors primarily exploiting the membrane-fusion mechanism and polymer vectors mainly endocytosis-mediated ***,only lipid vectors have been advanced through to their clinical use in the delivery of,for example,the first siRNA drug and the first mRNA *** success of lipid vectors for RNA delivery has motivated research for further innovative materials as delivery ***,we have pioneered lipid/dendrimer conjugates,referred to as amphiphilic dendrimers,for siRNA delivery with the view to harnessing the delivery advantages of both lipid and polymer vectors while enjoying the unique structural features of *** amphiphilic dendrimer vectors are lipid/dendrimer hybrids and are thus able to mimic lipid vectors and exploit membranefusion-mediated delivery,while simultaneously retaining the multivalent properties of polymer vectors that allow endocytosis-based *** addition,they have precisely controllable and stable nanosized chemical structures and offer nanotechnology-based *** amphiphilic dendrimer vectors share two important elements:chemical hydrophilic

关键词： breakthrough retaining desired

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Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies

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Acta Pharmaceutica Sinica B 2021年第4期11卷 886-902页

作者： Yongchao Wang Jinjin Wang Dandan Zhu Yufei Wang Guangchao Qing Yuxuan Zhang xiaoxuan liu Xing-Jie Liang State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug DiscoveryCenter of Advanced Pharmaceutics and BiomaterialsChina Pharmaceutical UniversityNanjing 210009China Laboratory of Controllable Nanopharmaceuticals Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Current advances of immunotherapy have greatly changed the way of cancer *** the same time,a great number of nanoparticle-based cancer immunotherapies(NBCIs)have also been explored to elicit potent immune responses against ***,few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of in vivo fate of nanoparticles(NPs)for cancer *** for cancer immunotherapy mainly target the immune organs or immune cells to enable effcient antitumor immune *** physicochemical properties of NPs including size,shape,elasticity and surface properties directly affect their interaction with immune systems as well as their in vivo fate and therapeutic ***,systematic analysis of the physicochemical properties and their effect on in vivo fate is urgently *** this review,we frst recapitulate the fundamentals for the in vivo fate of NBCIs including physio-anatomical features of lymphatic system and strategies to modulate immune ***,we highlight the effect of physicochemical properties on their in vivo fate including lymph nodes(LNs)drainage,cellular uptake and intracellular *** and opportunities for rational design of NPs for cancer immunotherapy are also discussed in detail.

关键词： Physicochemical properties Nanoparticle-based cancer immunotherapies Cancer treatment In vivo fate Immune responses Lymph nodes drainage Cellular uptake Intracellular transfer

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Annual 30-m land use/land cover maps of China for 1980–2015 from the integration of AVHRR, MODIS and Landsat data using the BFAST algorithm

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Science China Earth Sciences 2020年第9期63卷 1390-1407页

作者： Yidi XU Le YU Dailiang PENG Jiyao ZHAO Yuqi CHENG xiaoxuan liu Wei LI Ran MENG Xinliang XU Peng GONG Ministry of Education Key Laboratory for Earth System Modeling Department of Earth System ScienceTsinghua UniversityBeijing 100084China Ministry of Education Ecological Field Station for East Asian Migratory Birds Beijing 100084China Key Laboratory of Digital Earth Science Institute of Remote Sensing and Digital EarthChinese Academy of SciencesBeijing 100094China College of Natural Resources and Environment Huazhong Agricultural UniversityWuhan 430070China State Key Laboratory of Resources and Environmental Information Systems Institute of Geographical Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China

Annual land use land cover(LULC)change information at medium spatial resolution(*** 30 m)is required in numerous subjects,such as biophysical modelling,land management and global change *** LULC information,however,is usually not available at continental or national scale due to reasons such as insufficient remote sensing data coverage or lack of computational *** we integrate high temporal resolution and coarse spatial resolution satellite images(i.e.,Moderate Resolution Imaging Spectroradiometer(MODIS)and Global Inventory Modelling and Mapping Studies(GIMMS)normalized difference vegetation index(NDVI))with high spatial resolution datasets(China’s Land-Use/cover Datasets(CLUDs)derived from 30-meter Landsat TM/ETM+/OLI)to generate reliable annual nominal 30 m LULC maps for the whole of China between 1980 and *** also test the performance of a statistical based change detection algorithm(Breaks for Additive Seasonal and Trend),originally designed for tracking forest change,in classifying all-type LULC *** a result,a nominal 30 m annual land use/land cover datasets(CLUD-A)from 1980 to 2015 was developed for the whole *** mapping results were assessed with a change sample dataset,a regional annual validation sample set and a three-year China sample *** the detected change years,75.61%matched the exact time of conversion within±1 *** mapping results provided a detail process of urbanization,deforestation,afforestation,water and cropland dynamics over the past 36 *** consistent characterization of land change dynamics for China can be further used in scientific research and to support land management for policy-makers.

关键词： Land use land cover(LULC) Breaks for Additive Seasonal and Trend(BFAST) Change detection Annual China

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Synthesis of Biodegradable Block Copolymer Acyl-Imine with Catalyst of Zinc Powder

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Wuhan University Journal of Natural Sciences 2008年第2期13卷 217-220页

作者： ZHONG Min BAI Yu LI Wei liu xiaoxuan QU Fanqi College of Chemistry and Molecular Sciences WuhanUniversity Wuhan 430072 Hubei China College of Xinyang Profession Technology Xinyang464000 Henan China

This paper reported about a polymer of acyl imine synthesized by 3-morpholinone（M） and e-caprolactone（CL） with zinc powder as catalyst. The influence of reaction temperature, reaction time and monomer ratio on the copolymerization reaction was studied. Investigation of monomer reaction ratio and differential scanning calorimeter （DSC） indicated that the copolymer poly（3-morpholinone-e-caprolactone） was a block copolymer, solubility in water, degradation characteristics in vitro and controlled release of 5-FU was also studied. The results showed the hydrophilicity of the copolymer increased with the increasing of M content in the copolymer. With the enhancement of hydrophilicity its degradation rate and drug releasing rate increased as well.

关键词： catalyst 3-morpholinone ε-caprolactone block copolymer degradation controlled release

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Fabrication and Excellent Antibacterial Activity of Well-defined CuO/Graphdiyne Nanostructure

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Chemical Research in Chinese Universities 2021年第6期37卷 1341-1347页

作者： PAN Chuanqi liu xiaoxuan ZHANG Xiang MAO Feihong XU Peiyan ZHU Yuhua DENG Hongtao LUO Zhu SUN Hongwei ZHANG Lizhi GUO Yanbing Key Laboratory of Pesticide&Chemical Biology Ministry of EducationInstitute of Environmental and Applied ChemistryCollege of ChemistryCentral China Normal UniversityWuhan430079P.R.China

Copper oxide(CuO),due to its low cost,good chemical and physical stability,has recently been given special attention as a potential candidate for antibacterial ***,developing novel CuO nanocomposites with improved antibacterial property and unraveling the interface promotion mechanism has been a fundamental challenge for ***,well-defined CuO/graphdiyne(CuO/GDY)nanostructures with uniformly anchored CuO nanoparticles(ca.4.5 nm)have been *** CuO/GDY nanostructure exhibited superior *** inactivation efficiency,which is nearly 19 times and 7.9 times higher than the bare GDY and commercial CuO,*** improved *** inactivation performance was mainly due to the increased reactive·O_(2)−species generated by the activation of molecular O2 over CuO/GDY *** findings demonstrate the efficient antibacterial activity of well-defined CuO/GDY nanostructures and provide insights on the development of efficient GDY-based antibacterial materials.

关键词： Graphdiyne CuO/GDY nanocomposite Escherichia coli Antibacterial Superoxide radical

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促进企业创新的治理机制

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经济与管理研究 2021年第12期42卷 77-92页

作者：刘小玄南京财经大学南京210003 中国社会科学院经济研究所北京100101

企业的全要素生产率决定于企业创新产生的价值增值,而创新则来源于企业家对于投入要素的最佳配置和要素最大潜力的释放。企业家的控制权是推动企业创新的主导力量。相对于所有权而言,企业家的控制权更为重要,因为这种主导权有助于人力... 详细信息

企业的全要素生产率决定于企业创新产生的价值增值,而创新则来源于企业家对于投入要素的最佳配置和要素最大潜力的释放。企业家的控制权是推动企业创新的主导力量。相对于所有权而言,企业家的控制权更为重要,因为这种主导权有助于人力资本把握使企业变得更有价值的机会,赋予企业创造关键资源的创新能力,即获得专业化人力资本的能力,这是一种隐形投资,其效果往往在事后表现出来。明智的选择应当是善于在事先就发现和运用这个主导力量来推动企业创新,在面临不确定性市场的情况下,赋予企业家过程决策和事后决策的自由裁量权。企业的多元产权要素形成的共担风险模式,要求以无法直接定价的人力资本与可直接定价的其他投入要素地有机结合与合理配置。这种隐性人力资本投入得越有效或越多,则创新的潜力越大,因而越需要受到激励。

关键词：创新企业家控制权人力资本公司治理

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