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,ZL201810185988.1
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,ZL2015104104733
10、一种组织工程皮肤的制备方法,发明专利,ZL2015104104729
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。