一、简介
本团队致力于多糖类生物活性大分子与蛋白质之间相互作用的研究,并围绕(1)功能性多糖制备;(2)多糖-蛋白质医用材料;(3)多糖药物传递系统,在癌症、心脑血管疾病的治疗,以及免疫疗法开展工作。
a)化学/酶法合成结构确定的糖胺聚糖:糖胺聚糖的特殊生物活性与其化学结构有关,为了获得结构可调,活性功能明确可控的多糖,利用硫酸基修饰的硫酸基转移酶、调节分子量用的肝素裂解酶等工具酶对肝素、硫酸软骨素等糖胺聚糖进行结构,开发一系列结构确定的单糖或多糖。此外,利用化学方法将单糖或多糖共价嫁接到生物相容性优异的高分子上,制备一系列具有多价效应(multivalency)的含糖高分子。
b)糖胺聚糖的构效关系研究与药物开发:通过细胞和动物实验从(b)中的一系列单糖、多糖或含糖高分子中分别筛选出具有显著免疫活性、抗炎症活性、抗肿瘤转移、抗组织纤维化的活性物质,并研究其特殊结构与靶标受体间的作用关系,进而开发基于糖胺聚糖的新型制药。
c)糖胺聚糖基药物传递系统:糖胺聚糖能与多种蛋白或活性因子特异结合,譬如肝素和抗凝血酶、硫酸类肝素与纤维母细胞生长因子等。因此,这一部分工作,我们将深入开发能与特定肿瘤环境中蛋白结合的糖胺聚糖功能片段,利用这些片段制备或修饰药物载体,并考察多糖结构改变对给药系统载药等制剂学性质影响,继而通过细胞和动物实验评价药物载体的诊疗效率。
d)基于糖胺聚糖的仿生医用材料:糖胺聚糖是细胞外基质主要成分,具有极为优良的生物相容性、生物可降解性和生物学活性,譬如透明质酸具有较强的吸水性,能维持未分化脑细胞之间的水和状态,从而有利于神经细胞的迁移。因此,利用糖胺聚糖的这些特性可制备系列生物医用材料,例如生物支架、三维细胞水凝胶等,并评价其在软骨修复、血管再生、神经修复等领域的应用性能。
本团队拥有先进的实验室设施和配套的功能实验室,并拥有能满足开展教学与科研工作所需的仪器设备。研究室现有教授2名,副教授6名。近年来,主持或参与包括973、国家自然科学基金、省部级科技项目以及企业委托项目15项,在国内外发表研究论文130余篇,申请国际/国家发明专利40余项,其中授权14项。
二、研究室成员
教授:陈敬华;张燕
副教授:陈荆晓;周娟;邱立朋;许淑琴;张慧杰;杨漾;高敏
秘书:王睿
三、科研成果
近五年发表的代表性SCI论文
1. Zhi Cai, Yishu Yan, Juan Zhou, Yang Yang, Yan Zhang,* and Jinghua Chen*. Multifunctionalized Brush-Like Glycopolymers with High Affinity to P‑Selectin and Antitumor Metastasis Activity. Biomacromolecules, 2021, 22, 1177-1185.
2. Han Cui, Qimeng Wang, Ye Zhang, Mihail Barboiu,* Yan Zhang* and Jinghua Chen*. Double-network Heparin Dynamic Hydrogels:Dynagels as Antibacterial 3D Cell Culture Scaffolds. Chemistry - A European Journal, DOI: 10.1002/chem.202005376.
3. Juan Zhou, Yanzhe Wu, Xihe Zhang, Jiahui Lai, Yuanli Li, Jian Xing, Liping Teng,* and Jinghua Chen*. Enzyme Catalyzed Hydrogel as Versatile Bioadhesive for Tissue Wound Hemostasis, Bonding, and Continuous Repair, Biomacromolecules, 2021, DOI: 10.1021/acs.biomac.0c01329.
4. Mingyu Wang, Li Zhang, Yanfei Cai, Yang Yang, Lipeng Qiu, Yiting Shen, Jian Jin, Juan Zhou*, Jinghua Chen*. Bioengineered Human Serum Albumin Fusion Protein as Target/Enzyme/pH Three-Stage Propulsive Drug Vehicle for Tumor Therapy, ACS Nano, 2020, 14, 17405-17418.
5. Juan Zhou, Yuning Han, Yang Yang, Li Zhang, Hong Wang, Yiting Shen, Jiahui Lai, and Jinghua Chen*. Phospholipid-Decorated Glycogen Nanoparticles for Stimuli-Responsive Drug Release and Synergetic Chemophotothermal Therapy of Hepatocellular Carcinoma. ACS Applied Materials & Interfaces, 2020, 12, 23311-23322.
6. Yan Zhang, Mihail Barboiu*, Olof Ramström*, Jinghua Chen*. Surface-Directed Selection of Dynamic Constitutional Frameworks as an Optimized Microenvironment for Controlled Enzyme Activation, ACS Catalysis, 2020, 10: 1423-1427.
7. JunLing Song, ZhaoQian Huang, Jing Mao, WeiJun Chen, Bin Wang, FuWei Yang, ShenHuan Liu, HuiJie Zhang, LiPeng Qiu*, JingHua Chen*. A facile synthesis of uniform hollow MIL-125 titanium-based nanoplatform for endosomal esacpe and intracellular drug delivery, Chemical Engineering Journal, 2020, 396: 125246.
8. Yan Zhang, Ye Zhang, Han Cui, Mihail Barboiu*, Jinghua Chen*. Dynameric Collagen Self-healing Membranes with High MechanicalStrength for Effective Cell Grow Applications, Chemistry-A European Journal, DOI: 10.1002/chem.202003269.
9. Xihe Zhang, Juan Zhou*, Huiyan Ying, Yuting Zhou, Jiahui Lai, Jinghua Chen*. Glycogen as a Cross-Linking Agent of Collagen and Nanohydroxyapatite To Form Hydrogels for bMSC Differentiation, ACS Sustainable Chemistry & Engineering, 2020, 8: 2106-2114.
10. Yi Liu, Rui Wang, Shayang Chen, Zhujie Xu, Qiqi Wang, Peng Yuan, Yiyi Zhou, Yan Zhang, Jinghua Chen*. Heparan sulfate loaded polycaprolactone-hydroxyapatite scaffolds with 3D printing for bone defect repair, International Journal of Biological Macromolecules, 2020, 148: 153-162.
11. Yuning Han, Bin Hu, Mingyu Wang, Yang Yang, Li Zhang, Juan Zhou*, Jinghua Chen*. pH-Sensitive Tumor-Targeted Hyperbranched System Based on Glycogen Nanoparticles for Liver Cancer Therapy, Applied Materials Today, 2020, 18, 100521.
12. Zhujie Xu, Qiqi Wang, Yuyu Jiang, Rui Wang, Shayang Chen, Jingyu Zhu, Yan Zhang*, Jinghua Chen*. Selective regulation of RANKL/RANK/OPG pathway by heparan sulfate through the binding with estrogen receptor β in MC3T3-E1 cells, International Journal of Biological Macromolecules, 2020, 161: 1526-1534.
13. Huiyan Ying, Juan Zhou*, Mingyu Wang, Dandan Su, Qiaoqiao Ma, Guozhong Lv, Jinghua Chen*. In situ formed collagen-hyaluronic acid hydrogel as biomimetic dressing for promoting spontaneous wound healing. Materials science & engineering C. 2019, 101:487-498.
14. Kamel S. Ahmed, Xiaotian Shan, Jing Mao, Lipeng Qiu*, Jinghua Chen*. Derma roller microneedles-mediated transdermal delivery of doxorubicin and celecoxib co-loaded liposomes for enhancing the anticancer effect. Materials science & engineering C. 2019, 99: 1448-1458.
15. Lipeng Qiu, Xiaotian Shan, Miaomiao Long, Kamel S. Ahmed, Li Zhao, Jing Mao, Huijie Zhang, Changling Sun, Chongzhao You, Guozhong Lv, Jinghua Chen*. Elucidation of cellular uptake and intracellular trafficking of heparosan polysaccharide-based micelles in various cancer cells. International Journal of Biological Macromolecules. 2019, 130:755-764.
16. Dandan Su, Juan Zhou*, Kamel S. Ahmed, Qiaoqiao Ma, Guozhong Lv, Jinghua Chen*. Fabrication and characterization of collagen-heparin-polypyrrole composite conductive film for neural scaffold. International Journal of Biological Macromolecules. 2019, 129:895-903.
17. Zhou, Juan; Ying, Huiyan; Wang, Mingyu; Su, Dandan; Lu, Guozhong; Chen, Jinghua*. Dual layer collagen-GAG conduit that mimic vascular scaffold and promote blood vessel cells adhesion, proliferation and elongation. Materials science & engineering C. 2018, 92:447-452.
18. Juan Zhou, Mingyu Wang, Huiyan Ying, Dandan Su, Huijie Zhang, Guozhong Lu, Jinghua Chen*. Extracellular Matrix Component Shelled Nanoparticles as Dual Enzyme-Responsive Drug Delivery Vehicles for Cancer Therapy. ACS Biomaterials Science & Engineering. 2018, 4:2404-2411.
19. Huijie Zhang, Ting Cheng, Li Lai, Shuhao Deng, Ruixi Yu, Lipeng Qiu, Juan Zhou, Guozhong Lu, Chunyi Zhi, Jinghua Chen*. BN nanospheres functionalized with mesoporous silica for enhancing CpG oligodeoxynucleotide-mediated cancer. Nanoscale. 2018,10: 14516-14524.
20. Huijie Zhang, Mengxia Peng, Ting Cheng, Peng Zhao, Lipeng Qiu, Juan Zhou, Guozhong Lu, Jinghua Chen*. Silver nanoparticles-doped collagen–alginate antimicrobial biocomposite as potential wound dressing. Journal of Materials Science. 2018,53:14944-14952.
21. Jing Wu, Jiayi Yuan, Baotong Ye, Yaling Wu, Zheng Xu, Jinghua Chen*, Jingxiao Chen*. Dual-Responsive Core Crosslinking Glycopolymer-Drug Conjugates Nanoparticles for Precise Hepatocarcinoma Therapy. Frontiers in Pharmacology. 2018,9:663(1-12).
22. Ye Baotong; Cai Zhi; Wu Jing; Lin Xin; Chen Jingxiao*; Chen Jinghua*, Preparation of Sulfonated Galactose-based Glycopolymers and Interactions with Lectins. Acta Polymerica Sinica, 2018,4:490-498.
23. Qiu lipeng, Gelu, Long miaomiao, Wang Qian, Zhang Yan, Shan xiaotian, Chen jingxiao, Zhang Huijie, Li xiaomei, Lv guozhong,Chen jinghua*. Designing heparan sulfate-based biocompatible polymers and their application for intracellular stimuli-sensitive drug. Materials science & engineering C. 2018,94:465-476.
24. Yishu Yan, Yuan Lu, Xiaoni Liu, Yan Zhang, Jinghua Chen*. pH-driven precise control of hybridization reaction kinetics for rapid DNA assay. Chemistry Select. 2018,3: 10646-10650.
25. Jing-Xiao Chen, Jing Yuan, Ya-Ling Wu, Ping Wang, Peng Zhao, Guo-Zhong Lv, Jinghua Chen*. Fabrication of tough poly(ethylene glycol)/collagen double network hydrogels for tissue engineering. Journal of Biomedical Materials Research Part A. 2018,106A: 192-200.
26. Kamel S. Ahmed, Saied A. Hussein, Abdelmoneim H. Ali, Sameh A. Korma, Qiu Lipeng, Chen Jinghua*, Liposome: composition, characterisation, preparation, and recent innovation in clinical applications. Journal of Drug Targeting. 2018,15:1-20.
27. Haitian Fu, Chao Deng, Liping Teng, Zhi Cai, JinghuaChen*, GuozhongLv. Effect of heparan sulfate mimetics from Escherichia coli K5 polysaccharide on SDF-1/CXCL12-induced endothelial. International Journal of Biological Macromolecules. 2017, 107: 2492-2500.
28. Lipeng Qiu, Mengqin Zhu, Kai Gong, Jinghua Chen*. pH-Sensitive degradable polymeric micelles for bio-triggered targeted anti-tumor drug delivery. Journal of Controlled Release. 2017, 259:5-195.
29. Chao Deng, Haitain Fu, Jingying Shang, Jinghua Chen*, Xin Xu. Dectin-1 mediates the immunoenhancement effect of the polysaccharide from dictyophora indusiata. International journal of biological macromolecules. 2017,109:369-374.
30. Huijie Zhang, Wei Chen, Kai Gong, Jinghua Chen*. Nanoscale zeolitic imidazolate framework-8 as efficient vehicles for enhanced delivery of CpG Oligodeoxynucleotides. Applied materials & interfaces, 2017, 9:31519-31525.
31. Shuqin Xu, Xuanyue Zhang, Bo Duan, Jinghua Chen*. An engineering platform based on chitin-affinity immobilization for producing low molecular weight heparin. Carbohydrate polymers, 2017, 177:297-305.
32. Shuqin Xu, Meiling Qiu, Xuanyue Zhang, Jinghua Chen*. Expression and characterization of an enhanced recombinant heparinase I with chitin binding domain. International journal of biological macromolecules, 2017:105:1250-1258.
33. Lipeng Qiu, Mengqin Zhu, Kai Gong, Huanhuan Peng, Lu Ge, Li Zhao, Jinghua Chen*. PH-triggered degradable polymeric micelles for targeted anti-tumor drug delivery. Materials Science and Engineering C, 2017, 78: 912-922.
34. Haitian Fu, Liping Teng, Ruizhen Bai, Jinghua Chen*. Application of acellular intima from porcine thoracic aorta in full-thickness skin wound healing in a rat model. Materials Science and Engineering C, 2017, 71: 1135-1144.
35. Jingxiao Chen, Yuan Jing, Yaling Wu, Ping Wang, Peng Zhao, Guozhong Lv, Jinghua Chen*. Fabrication of tough poly (ethylene glycol)/collagen double network hydrogels for tissue engineering. Journal of biomedical materials research Part A, 2017, 43:89-93.
36. Li Yu, Xiaojuan Xu, Juan Zhou, Jinghua Chen*. Chain conformation and rheological behavior of exopolysaccharide from Bacillus mucilaginosus SM-01. Food Hydrocolloid, 2017, 65: 165-174.
37. Jingxiao Chen, Yu Shi, Yirang Zhang, Liping Teng, Jinghua Chen*. One-pot construction of boronate ester based pH-responsive micelle for combined cancer therapy. Colloids Surf B Biointerfaces, 2016, 143: 285-292.
38. Jingxiao Chen, Lujuan Cao, Yu Shi, Ping Wang, Jinghua Chen*. In situ supramolecular hydrogel based on hyaluronic acid and dextran derivatives as cell scaffold. Journal of biomedical materials research Part A, 2016, 104A: 2263-2270.
39. Lingpeng Qiu, Mengqin Zhu, Yan Huang, Kai Gong and Jinghua Chen*. Mechanisms of cellular uptake with hyaluronic acid-octadecylamine micelles as drug delivery nanocarriers. RSC Advances, 2016, 6(46):39896-39902.
40. Li Yu, Shuqin Xu, Chao Deng, Jinghua Chen*. Preparation and partial structural characterization of the exopolysaccharide from Bacillus mucilaginosus SM-01. Carbohydrate polymers, 2016, 146:217-223.
41. Chao Deng, Jingying Shang, Haitian Fu, Jinghua Chen*. Mechanism of the immunostimulatory activity by a polysaccharide from Dictyophora indusiata. International journal of biological macromolecules, 2016, 91:752-759.
42. Chao Deng, Yuanyuan Sun, Haitian Fu, Jinghua Chen*. Antioxidant and immunostimulatory activities of polysaccharides extracted from Tremella aurantialba mycelia. Molecular Medicine Reports, 2016, 14(5): 4857-4864.
授权专利
1、Enzymatic synthesis of sulfated polysaccharides. 国际专利, US201213417641 20120312; US20080920319 20081209; WO2006US18778 20060512; US20050680392P 20050512.
2、Enzymatic synthesis of sulfated polysaccharides without iduronic acid residues. 国际专利, US20080178434 20080723; US20070961716P 20070723.
3、Purified and isolated heparan sulfate 3-O-sulfotransferase isoform 5 nucleic acids and polypeptides and therapeutic and screening methods using SAME. 国际专利, WO2003US21094 20030707; US20020394199P 20020705; US20050520341 20051020.
4、一种硫酸化肝素二糖接枝聚甲基丙烯酰乙醇胺及其制备方法,发明专利,ZL 2018103998592
5、硫酸化肝素二糖接枝聚甲基丙烯酰乙醇胺的用途,发明专利,ZL 2018103991663
6、一种生物粘合剂及其制备方法,发明专利,ZL 2012104644704
7、一种注射用多功能复合型水凝胶及其制备方法,发明专利,ZL 201810185988.1
8、一种以胶原纺丝和透明质酸为基材的粘附性仿生凝胶,发明专利,ZL201910046995.8
9、一种人工异种抗菌皮肤的制备方法,发明专利,ZL 2015104104733
10、一种组织工程皮肤的制备方法,发明专利,ZL 2015104104729
11、一种猪胸主动脉中提取水不溶性胶原蛋白的方法,发明专利,ZL2015102378014
12、一种具有自抗炎功能的胶原基海绵伤口敷料的制备方法. ZL201310123232.1
13、一种多通道微流装置制备纤维素微球的方法,发明专利,ZL 2013101028936
14、一种制备肝素修饰的金纳米粒子的方法. ZL200910024843.4, 2013
四、科研成果(省部级以上科研及人才项目)
国家自然科学基金11项;省部级人才支持计划1项,教育部博士点基金1项;江苏省自然科学基金4项;江苏省产学研研究项目1项。江苏省特聘教授1位,江苏省双创博士3位。