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Co-delivery of Andrographolide and Notch1-targeted siRNA to Macrophages with Polymer-based Nanocarrier for Enhanced Anti-inflammation

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Chinese Journal of Polymer Science 2018年第12期36卷 1312-1320页

作者： Teng Wu Min Tan Heng-Ye Gong Yong Wang xin-tao shuai PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-Sen University Guangzhou 510275 China Center of Biomedical Engineering Zhongshan School of Medicine Sun Yat-sen University Guangzhou 510080 China

Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly（ethylene glycol）-block-poly（L-aspartic acid） grafted with diethylenetriamine, lysine and cholic acid （PEG-PAsp（DETA）-Lys-CA2） polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide （LPS）-activated interleukin-6 （IL-6） and monocytes chemotactic protein 1 （MCP-1） expression as well as blocked nuclear factor-rd3 （NF-rd3） signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 （IL-10） and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.

关键词： Macrophages Anti-inflamatory Andrographolide Notchl siRNA

Co-delivery of Doxorubicin and Afatinib with pH-responsive Polymeric Nanovesicle for Enhanced Lung Cancer Therapy

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Chinese Journal of Polymer Science 2019年第12期37卷 1224-1233,I0006页

作者： Heng-Ye Gong Yan-Gui Chen xing-Su Yu Hong Xiao Jin-Peng Xiao Yong Wang xin-tao shuai PCFM Lab of Ministry of Education School of Materials Science and EngineeringSun Yat-Sen UniversityGuangzhou 510275China HEC Pharma Co. Ltd.Dongguan 523871China Reproductive Center Guangdong Women’s Health Care CenterGuangzhou 511400China

Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.

关键词： Nanovesicle Polymeric vector Combination therapy pH-responsive

Multifunctional Nanoplatform Based on pH-responsive Micelle Coated with Discontinuous Gold Shell for Cancer Photothermo-chemotherapy and Photoacoustic Tomography

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Chinese Journal of Polymer Science 2018年第10期36卷 1139-1149页

作者： Yi Huang Xiao-Xia Li Lu Zhang Xiao-Yan Chen Cheng-Bo Liu Jing-Qin Chen Yong Wang xin-tao shuai PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-Sen University Research Laboratory for Biomedical Optics and Molecular Imaging Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences

Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly（aspartic acid-butanediamine）-poly（2- （diisopropylamino）ethyl methacrylate）（PAsp（DAB）-PDPA） was synthesized and self-assembled into doxorubicin-loaded micelle, which was further used as a template to form a gold nanoshell. After fitrther modification with poly（ethylene glycol）, the resulting nanoplatform provided good biocompatibility and desirable photo-thermal conversion efficiency to facilitate photothermal therapy. Meanwhile the nanoparticle also exhibited pH sensitivity, which prevented drug loss while circulating in the blood but enabled rapid drug release after endocytosis. An improved effect was achieved with the combination of photothermal therapy and chemotherapy. In addition, systemic delivery of the nanoplatform could be monitored by photoacoustic tomography. Thereby, this multifunctional nanoplatform would be highly potential for the diagnosis and therapy of cancer.

关键词： Gold nanoshell Photoacoustic tomography Photothermo-chemotherapy pH-sensitive micelle

A Dual Ligand Targeted Nanoprobe with High MRI Sensitivity for Diagnosis of Breast Cancer

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Chinese Journal of Polymer Science 2014年第3期32卷 321-332页

作者： Fa-ming Gong Zuo-quan Zhang Xiao-dong Chen Lu Zhang xing-su Yu Qi-hua Yang xin-tao shuai 梁碧玲程度 PCFM Lab of Ministry of Education School of Chemistry and Chemical EngineeringSun Yat-sen University Department of Radiology Sun Yat-sen Memorial HospitalSun Yat-sen University Department of Radiology The Fifth Affiliated HospitalSun Yat-sen University Center of Biomedical Engineering Zhongshan School of MedicineSun Yat-Sen University

Antibody targeted delivery is an effective strategy to improve the diagnostic imaging outcome of nanoscale imaging agents in the focal areas. Dual targeting micelles encapsulating superparamagnetic iron oxide were prepared from the amphiphilic block copolymer poly（ethylene glycol）-poly（e-caprolactone）（PEG-b-PCL） with different targeting ligands cRGD and scFv-ErbB single chain antibody conjugated to the distal ends of PEG block. The breast cancer animal model was established by subcutaneous injecting the BT474 cells into the BALB/c-nu female nude mice and then employed to assess the potential of the dual ligand targeted magnetic micelles as a novel MRI contrast agent on a 1.5 T clinical MR/scanner. The T2 signal intensity of the tumor in animals receiving the dual ligand targeted magnetic micelles via tail vein decreased more significantly than the single ligand targeted and nontargeted magnetic micelles. These results indicate that the dual ligand targeted magnetic micelles, cRGD/scFv-ErbB-PEG-PCL-SPION, have great potential to act as a new type of effective nanoscale MRI contrast agent for early diagnosis of breast cancer.

关键词： Block copolymer micelle Superparamagnetic iron oxide （SPI0） Breast cancer Magnetic resonance imaging（MRI） Herceptin c（Arg-Gly-Asp-d-Phe-Lys）（cRGDfK）.

SYNTHESIS OF NOVEL BLOCK COPOLYMERS OF POLY(3-HYDROXYBUTYRIC ACID)WITH POLY(ETHYLENE GLYCOL)THROUGH ANIONIC POLYMERISATION

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Chinese Journal of Polymer Science 2000年第1期18卷 19-23页

作者： xin-tao shuai Zbigniew Jedlinski Qiang Luo Nozirow Farhod Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China Institute of Polymer Chemistry, Polish Academy of Sciences, 41-800 Zabrze, Poland Institute of Synthetic Fibre, Chinese Academy of Textile Sciences, Beijing 100025, China 中科院化学所北京波兰科学院高分子化学所波兰纺织科学研究院北京 100025

A novel kind of copolymer with ABA-type block structure was synthesized by anionic ring-opening polymerization of beta-butyrolactone (beta-BL) in the presence of a PEG-based dicarboxylates as macroinitiators which were prepared by the esterification of aliphatic cyclic anhydride and poly(ethylene glycol) (PEG) oligomers (M-n = 2000, 4000 and 6000) and conversion of potassium dicarboxylates. The resultant copolymers as well as the intermediates were characterized by IR, H-1-NMR and GPC.

关键词： block copolymer poly(ethylene glycol) poly(3-hydroxybutyric acid)

PEI-PEG as a siRNA Genetic Vector Demonstrating Interference in the Expression of CD44v6 Protein in Gastric Cancer Cells

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Clinical oncology and cancer resexreh 2010年第3期7卷 187-192页

作者： Kai-hong HUANG Ying WU Yin-ting CHEN Hui DENG Guo-da LIAN xin-tao shuai Department of Gastroenterology 2nd Affiliated Hospital Sun Yat-Sen University Guangzhou 510120 Guangdong Province China. School of Chemistry and Chemical Engineering Sun Yat-Sen University Guangzhou 510275 Guangdong Province China.

To investigate the effect of polyethylene imine glycol (PEI-PEG)/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay (mononuclear cell direct cytotoxicity assay), and the downregulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was (80.4 ± 5.6)% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to (59.7 ± 3.0)% aft er siRNA-CD44v6 was inhibited. PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection efficiency, less cytotoxicity and an easily alterable vector structure.

关键词： siRNA 胃癌细胞聚乙二醇 RNA干扰蛋白基因表达载体纳米复合材料转染效率

Photoinduced copper-catalyzed alkoxyl radical-triggered ring-expansion/aminocarbonylation cascade

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Chinese Chemical Letters 2024年第6期35卷 331-336页

作者： Jing-Qi tao shuai Liu Tian-Yu Zhang Hong xin Xu Yang xin-Hua Duan Li-Na Guo Department of Chemistry School of ChemistryXi’an Key Laboratory of Sustainable Energy Material Chemistry and Engineering Research Center of Energy Storage Materials and DevicesMinistry of EducationXi’an Jiaotong UniversityXi’an 710049China School of Electrical Engineering Xi’an Jiaotong UniversityXi’an 710049China State Key Laboratory of Applied Organic Chemistry Lanzhou UniversityLanzhou 730000China

A photoinduced copper-catalyzed alkoxyl triggered C-C bond cleavage/aminocarbonylation cascade is presented.Through adjusting the structure of alkoxyl radical precursors,functionalized lactones and ketoamides were synthesized with good yields and excellent functional group tolerance under redox-neutral conditions.Notably,this protocol enables the integration of lactone fragments with many amine drugs and drug fragments.

关键词： Copper catalysis Ring-expansion Aminocarbonylatioin Macrolactones Keto-amides

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis

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World Journal of Gastroenterology 2024年第12期30卷 1764-1776页

作者： tao Zhang shuai Zhu Geng-Wen Huang Department of General Surgery Xiangya HospitalCentral South UniversityChangsha 410005HunanChina. National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410005HunanChina.

BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.

关键词： Acute pancreatitis Autophagy ZKSCAN3 N6-methyladenosine ALKBH5

Electrochemical anodic oxidation assisted fabrication of memristors

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International Journal of Extreme Manufacturing 2024年第3期6卷 250-272页

作者： shuai-Bin Hua Tian Jin xin Guo School of Materials Science and Engineering State Key Laboratory of Material Processing and Die&Mould TechnologyHuazhong University of Science and TechnologyWuhan 430074People’s Republic of China

Owing to the advantages of simple structure,low power consumption and high-density integration,memristors or memristive devices are attracting increasing attention in the fields such as next generation non-volatile memories,neuromorphic computation and data encryption.However,the deposition of memristive films often requires expensive equipment,strict vacuum conditions,high energy consumption,and extended processing times.In contrast,electrochemical anodizing can produce metal oxide films quickly(e.g.10 s) under ambient conditions.By means of the anodizing technique,oxide films,oxide nanotubes,nanowires and nanodots can be fabricated to prepare memristors.Oxide film thickness,nanostructures,defect concentrations,etc,can be varied to regulate device performances by adjusting oxidation parameters such as voltage,current and time.Thus memristors fabricated by the anodic oxidation technique can achieve high device consistency,low variation,and ultrahigh yield rate.This article provides a comprehensive review of the research progress in the field of anodic oxidation assisted fabrication of memristors.Firstly,the principle of anodic oxidation is introduced;then,different types of memristors produced by anodic oxidation and their applications are presented;finally,features and challenges of anodic oxidation for memristor production are elaborated.

关键词： anodic oxidation anodized aluminium oxide memristor resistive switching electrical properties