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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 ***-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these *** 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 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)*** 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 *** 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).

Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery

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Chinese Journal of Polymer Science 2022年第9期40卷 1071-1079页

作者： Rong-Ze Wang Si Huang Qiao-Yun Zhang xing-Su Yu Ke-Ze Hong Jian-Rong Cao Hong Xiao Yong Wang xin-tao shuai College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China Nanomedicine Research Center The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of Reproductive Medical Center Guangdong Women and Children HospitalGuangzhou 511400China

RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer ***,an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical ***,we constructed a polymeric vector labeled with superparamagnetic iron oxide(SPIO)for magnetic resonance imaging(MRI)visible siRNA *** antibody was also modified to the surface of nanodrug to enhance the delivery *** results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious ***,both in vitro and in vivo studies evidenced the vector could effectively deliver siRNA into tumor cells,exert highly interfering effect,and show potent MR imaging *** study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.

关键词： Polymeric vector siRNA delivery Magnetic resonance imaging visible Tumor targeting

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 researeh 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.

OBJECTIVE 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. METHODS 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 down-regulation 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. RESULTS 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）% after siRNA-CD44v6 was inhibited. CONCLUSION 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 e. ciency, less cytotoxicit

关键词： siRNA PEI-PEG transfection efficiency cytotoxicity CD44v6 gene gastric cancer cell

Gradient maturation experiment on hairs implies taphonomic changes in fossil hairs

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Science China Earth Sciences 2025年第1期68卷 62-73页

作者： xin LI Yibo ZHOU tao ZHAO xingjian HE Yanhong PAN State Key Laboratory for Mineral Deposits Research Center for Critical Earth Material Cycling Centre for Research and Education on Biological Evolution and Environment and Frontiers Science School of Earth Sciences and Engineering Nanjing University Institute of Palaeontology Yunnan Key Laboratory of Earth System Science Yunnan Key Laboratory for PalaeobiologyYunnan University

Mammalian hair, as a key feature related to endothermy, physical protection, and camouflage, has a long geohistorical record that dates back even to the Mesozoic. However, the limited information on the taphonomy of hair hinders the understanding of its evolutionary significance in deep time. To address this, we conducted taphonomic experiments to simulate the transformation process of black hair. The changes in the morphological structure, microscopic characteristics, and chemical composition of hair during the simulated fossilization process were documented by scanning electron microscopy, Fourier transform infrared(FTIR) spectroscopy, and Raman spectroscopy. Our results revealed that damage to the morphology of hair began at a mild temperature(150–175°C), and hair transformed into a fluid-like mass at a relatively high temperature(200°C). In addition, the morphological structure of melanosomes had relatively greater preservation potential than keratins did, and the microscopic features of melanosomes were persistently stable. The Raman and FTIR spectra indicated that the characteristic melanin and keratin peaks changed as the temperature increased. Although the chemical signals were not lost completely, the variations in the characteristic amide bands in the FTIR spectra indicate that the keratins severely degraded at high temperatures(>200°C), whereas the characteristic melanin bands in the Raman spectra suggested that melanin signals were still recognizable, even at high temperatures(>200°C). These results were confirmed by principal component analysis(PCA) and principal component analysis linear discriminant analysis(PCA–LDA). In addition, the Raman signals of all the samples in the simulated experiments were distinguished from the signals of common geological carbonaceous materials(humic acid), which suggested that Raman spectroscopy can be used to detect melanin in fossils.

关键词： Mammalian hair Melanin Keratin Fossilization Experimental taphonomy

磁共振对比剂标记的聚合物传输siRNA抑制基因表达

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高分子学报 2015年第4期25卷 484-492页

作者：王卫娟肖洪程度帅心涛中山大学化学与化学工程学院聚合物复合材料及功能材料教育部重点实验室广州510275 中山大学中山医学院生物医学工程研究中心广州510275

二乙烯三胺(DETA)修饰生物可降解的聚乙二醇(PEG)-聚天冬氨酸(PAsp)两嵌段聚合物PEGPAsp,并通过配体交换将PEG-PAsp(DETA)修饰到磁共振(MR)对比剂SPIO表面,阳离子嵌段PAsp(DETA)可负载核酸分子siRNA,从而获得兼具MR显像和核酸传输功能... 详细信息

二乙烯三胺(DETA)修饰生物可降解的聚乙二醇(PEG)-聚天冬氨酸(PAsp)两嵌段聚合物PEGPAsp,并通过配体交换将PEG-PAsp(DETA)修饰到磁共振(MR)对比剂SPIO表面,阳离子嵌段PAsp(DETA)可负载核酸分子siRNA,从而获得兼具MR显像和核酸传输功能的生物可降解载体.细胞毒性研究证实该载体聚合物具有较好的生物安全性,可被肿瘤细胞高效吸收,且使转基因细胞株A549-Luc(恒定表达萤火虫荧光素酶)中荧光素酶的活性下调60%.MR成像也证实,SPIO经载体负载后,其横场弛豫率比游离的水溶性SPIO(WSPIO)提高了3倍以上,达到147 Fe(mmol/L)-1s-1,显著提高了磁共振的显像效果.

关键词：核酸传输载体联合输送 siRNA 磁共振对比剂

Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： xintian Ding Chun Chen Heng Zhao Bin Dai Lei Ye tao Song shuai Huang Jia Wang tao You Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2