张小宁 - 清华大学

个人简介

2014-2016 “十二五”863计划“基因治疗药物靶向递送关键技术及成药性”课题首席 2012-2016 国家发改委药品价格审评专家 2012年至今 CFDA国家医疗器械审评专家 2011年至今 CFDA国家药品审评专家 2008年至今中国药学会高级会员 2004.7至今清华大学医学院药剂学研究室负责人 2002.7-2004.7 清华大学生物科学与技术系二站博士后 2000.8-2002.7 清华大学物理系原子分子纳米科学教育部重点实验室博士后 1997.9-2000.7 北京理工大学工学博士 1994.9-1997.7 北京理工大学理学硕士 1989.9-1993.7 西安交通大学工学学士

研究领域

纳米生物医药技术及其新药成药性。研究基于肿瘤微环境的、具有靶向给药+联合用药+程序杀伤性能特征的纳米给药系统，以期实现：①靶向递送药物至肿瘤组织部位—②进入肿瘤细胞微环境定量共同释放药物—③药物协同作用并诱导细胞程序性凋亡。将该技术应用于难溶性药物肿瘤靶向纳米给药系统，基因治疗药物纳米给药系统，抗肿瘤多药耐药纳米给药系统，并进行相关新药的成药性及生物学效应研究 1. 难溶性药物肿瘤靶向纳米给药系统：将被动靶向与主动靶向相结合：a）采用新型纳米胶束载药技术和新型药用辅料，解决难溶性药物给药困难问题，并通过控制载药纳米粒尺寸大小，利用EPR被动靶向效应使载药纳米粒在肿瘤部位絮集； b）利用细胞表面肿瘤特异性受体，将其配体接枝修饰于载药纳米粒表面，增加药物特异性主动靶向递送转运，以实现提高药效和降低毒性作用目的。 2. 小核酸药物纳米递送系统：采用新型高分子材料载体和自组装技术，设计构建小核酸药物纳米递送系统，解决核酸药物体内的高效靶向递送、高效转染与胞内功能表达等关键难题，促进小核酸等基因治疗药物技术的发展与应用。 3. 抗肿瘤多药耐药靶向联合用药纳米给药系统：基于肿瘤靶向纳米给药技术，研究将具有抗肿瘤多药耐药和抗肿瘤作用的两种不同药理作用的药物（化药或核酸药物）制成复方纳米给药系统制剂进行联合用药，靶向递送复方药物至肿瘤微环境，使其按确定比例在肿瘤细胞胞内微环境内同时释放并发生药理协同作用，实现显著逆转肿瘤多药耐药性，增加药物敏感性和有效性。

近期论文

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1.Jun Li, Jing Liu, Nana Guo, Xiaoning Zhang*. Reversal of multidrug resistance in breast cancer MCF-7/ADR cells by h-R3-siMDR1-PAMAM complexes. International Journal of Pharmaceutics. 2016, 511(1): 436-445. 2.Jun Li, Lei Chen, Nan Liu, Shengnan Li, Yanli Hao, Xiaoning Zhang *. EGF-coated nano-dendriplexes for tumor-targeted nucleic acid delivery in vivo. Drug Delivery. 3(5), 1718-1725, 2016. 3.Jun Li, Jing Liu, Shengnan Li, Yanli Hao, Lei Chen, Xiaoning Zhang*. Antibody h-R3 mediated siRNA has excellent endosomal escape and tumor targeted delivery ability, and represents efficient siPLK1 silencing and inhibition of cell proliferation, migration and invasion. Oncotarget. 2016, 7 (12): 13782-13796. 4.Jun Li, Shengnan Li, Songyun Xia, Jinfeng Feng, Yanli Hao, Lei Chen, Xiaoning Zhang*. Enhanced transfection efficiency and targeted delivery of self-assembling h-R3-dendriplexes in EGFR-overexpressing tumor cells. Oncotarget. 2015; 6: 26177-91. SCI, IF=6.359 (2014) 5.Yanli Hao*, Lan Wang, Jun Li, Nan Liu, Jinfeng Feng, Mojiao Zhao, Xiaoning Zhang*. Enhancement of solubility, transport across MDCK monolayer and oral absorption of pranlukast by preparing pranlukast-phospholipid complex. J. Biomedical Nanotechnology. 11(3), pp 469-477, 2015/3. SCI, IF=5.338 (2014) 6.Xiang Gao, Shimin Wang, BiLan Wang, Senyi Deng, Xiaoxiao Liu, XiaoNing Zhang, LinLi Luo, RangRang Fan, MingLi Xiang, Chao You, YuQuan Wei, ZhiYong Qian, Gang Guo.* Improving the anti-ovarian cancer activity of docetaxel with biodegradable self-assembly micelles through various evaluations. Biomaterials 53 (2015) 646-658. SCI, IF=8.557 (2014) 7.Cheng, Qiang; *Huang, Yuanyu; Zheng, Hua; Wei, Tuo; Zheng, Shuquan; Huo, Shuaidong; Wang, Xiaoxia; Du, Quan; Zhang, Xiaoning; Zhang, Hong-Yan; Liang, Xing-Jie; Wang, Chun; Tang, Rupei; Liang, Zicai*. The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA . BIOMATERIALS, 34(12), pp 3120-3131, 2013/4. SCI,IF=8.557 (2014) 8.Mingshu Ma, Yanli Hao*, Nan Liu, Zhe Yin, Lan Wang, Xing-Jie Liang, Xiaoning Zhang*. A novel lipid-based nano-micelle of docetaxel: evaluated antitumor efficiency and biodistribution with optical imaging in vivo. In J Nanomedicine ,7, pp 3389-3398, 2012. 9.Zhe Yin, Nan Liu, Mingshu Ma, Lan Wang, Xing-Jie Liang, Yanli Hao*, Xiaoning Zhang*. A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA and activated PAMAM dendrimers, In J Nanomedicine 7, pp 4625-4635, 2012. 10.Nan Liu, Yanli Hao*, Zhe Yin, Mingshu Ma, Lan Wang, Xiaoning Zhang*. Self-Assembled Human Serum Albumin-Coated Complexes for Gene Delivery with Improved Transfection. Die Pharmazie, 67(2), pp 174-181, 2012/2. 11.Lan Wang, Yanli Hao*, Nan Liu, Zhe Yin, Mingshu Ma, Xiaoning Zhang*. Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method. Drug Development and Industrial Pharmacy, 2012, 38(11):1381-1389