张小宁

张小宁，男，副研究员，1971年10月生。1989～1993年西安交通大学本科；1994～2000年北京理工大学硕士、博士；2000～2002年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；2002～2004年清华大学生物科学与技术系二站博士后；2004年至今清华大学医学院任药剂学研究室负责人。SFDA国家药品审评专家；国家发改委药品价格审评专家；重大新药创制项目审评专家；国家自然科学基金项目审评专家；中国药学会高级会员。

科研领域

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。

研究方向

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学作用的药物（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。

承担项目

“重大新药创制”，“973计划”子课题，“863计划”，NSFC，企业横向等课题。

发表论文

1. Keyang Huang, Huili Ma, Juan Liu, Shuaidong Huo, Anil Kumar, Tuo Wei, Xu Zhang, Shubin Jin, Yaling Gan, Paul C. Wang, Shengtai He*, Xiaoning Zhang*, and Xing-Jie Liang*. Size-Dependent Localization and Penetration of Ultrasmall Gold Nanoparticles in Cancer Cells, Multicellular Spheroids, and Tumors in vivo ACS NANO, 6(5), pp 4483-4493, 2012.

2. 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.

3. 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 西妥昔单抗, 脱氧核糖核酸 and activated PAMAM dendrimers, In J Nanomedicine 7, pp 4625-4635, 2012.

4. 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.

5. 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-压强 homogenizing method. Drug Development and Industrial Pharmacy, 2012 (in press, doi:10.3109/03639045.2011.652636)

6. Xue Xue, Song You, Qiang Zhang, Yan Wu, Guo-zhang Zou, Paul C. Wang, Yu-liang Zhao, Yan Xu, Lee Jia, Xiaoning Zhang, Xing-Jie Liang*.Mitaplatin Increases Sensitivity of Tumor Cells to Cisplatin by Inducing Mitochondrial Dys函数 Molecular Pharmaceutics, 2012, 9(3), 634−644

7. Xiaowei Ma, Yanyang Wu, Shubin Jin, Yuan Tian, Xiaoning Zhang, Yuliang Zhao, Li Yu, Xingjie Liang*. Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. ACS NANO, 2011, 5(11):8629-8639

8. Feng-Yun J. Huang, Te-Wei Lee, Chih-Hao K. Kao, Chih-Hsien Chang, Xiaoning Zhang, Wan-Yu Lee, Wan-Jou Chen, Shu-Chi Wang, and Jem-Mau Lo. Imaging, Autoradiography, and Biodistribution of 188Re-Labeled PEGylated Nanoliposome in Orthotopic Glioma Bearing Rat Model.Cancer Biotherapy \u0026 Radiopharmaceuticals. 2011, 26(6): 717-725.

9. Mi Wang, Yue Yuan, Yang Gao, Hongmei Ma, Hongtao Xu，Xiaoning Zhang, Weisan pan*. Preparation and characterization of 5- fluorouracil pHsensitive niosome and its tumor targeted evaluation: in vitro and in vivo Drug Development and Industrial Pharmacy, 38(9), pp 1134-1141, 2012.

10. Hongtao Xu, Ling He, Shu fangNie, Jin Guan, XiaoningZhang, Xing gangYang, Weisan pan*. Optimized preparation of vinpocetine proliposomes by a novel method and in vivo evaluation of its pharmacokinetics in New Zealand rabbits. J. Controlled Release, 2009, Nov 16; 140(1):61-8.

11. Wei Wei, Sanjun Shi, Jie Liu, Xun Sun, Ke Ren, Dong Zhao, Xiaoning Zhang, Zhirong Zhang, Tao Gong. Lipid nanoparticles loaded with 10-hydroxycamptothecin-phospholipid complex developed for clinical application. J. Drug Targeting 2010,18(7):557-566.

12. Xiaoyu Chen, Xun Sun, Ke Ren, Xiaoning Zhang*, Zhirong Zhang, Tao Gong*. Enhanced aqueous solubility and bioavailability of capsaicin by the preparation of inclusion complex. Arzneimittel-Forschung (Drug Research)2010,60 (9): 571-574

13. Xuan Qin, Yang Yang, Tingting Fan, Tao Gong, Xiaoning Zhang, Yuan Huang*. Preparation, characterization and in vivo evaluation of bergenin phospholipids complex. ACTA Pharmac奥林匹克里昂女子足球队 Sin. 2010, 31(1):127-136.

14. Chun-Yang 壮族; Ning Li; Mi Wang; XiaoNing Zhang; Wei-San pan; Jun-Jie Peng; Yu-Sheng Pan; Xin Tang. Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. International Journal of Phamarceutics, 2010, 394(1-2):179-185.

15. Fang Fang, Changyang Gong, Zhiyong Qian, Xiaoning Zhang, Maling Gou, Chao you, Liangxue Zhou, Jiagang Liu, Yu Zhang, Gang Guo, Yingchun Gu, Feng Luo, Lijuan Chen, Xia Zhao, Yuquan Wei*. Honokiol Nanoparticles in Thermosensitive Hydrogel: Therapeutic Effects on Malignant Pleural Effusion. ACS-NANO 2009, 3 (12):4080-4088

16. Shaozhi Fu, Gang Guo, Changyang Gong, Shi Zeng, Hang Liang, Feng Luo, Xiaoning Zhang, Xia Zhao, Yuquan Wei, Zhiyong Qian*. Injectable Biodegradable Thermosensitive Hydrogel Composite for Orthopedic Tissue Engineering. 1. Preparation and Characterization of Nanohydroxyapatite/Poly(ethyleneglycol)-Poly(ε-caprolactone)-Poly(乙烯 glycol) Hydrogel Nanocomposites. J. Phys. Chem. B. 2009, 113 (52):16518–16525

17.Huiming Lai, Feng Zhu, Wenmin Yuan, Na He, Zhirong Zhang, Xiaoning Zhang, Qin He. Development of multipleunit colon-targeted drug delivery system by using alginate: in vitro and in vivo evaluation. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 37(11), pp 1347-1356, 2011/11.

18. Xuanmiao Zhang, Xun Sun, Jilong Li, Xiaoning Zhang, Tao Gong, Zhirong Zhang. Lipid nanoemulsions loaded with doxorubicin-oleic acid ionic complex: characterization, in vitro and in vivo studies. PHARMAZIE, 66(7), pp 496-505, 2011/7.

19. 孙敏敏，郝艳丽，文，刘楠，马茗舒，殷哲，聂尚海，张小宁*. 白蛋白紫杉醇聚合物胶束抑瘤效果研究. 中国药学杂志, 2011, 46(3):55-59

20. 郝艳丽，王兰，马茗舒，刘楠，殷哲，张小宁*. 油纳米乳剂对急性高脂血症小鼠血脂的影响。中国农业科技导报，2011,13(1):94-97

21. 王兰，郝艳丽，刘楠，马茗舒，张小宁. 星点设计效应面法优化普伦斯特磷脂复合物的制备. 中国医药工业杂志, 2011, 42(11):815-818

22. 邰文，孙敏敏，刘楠，黄志起，聂尚海，郝艳丽*,张小宁*. 应用动物活体生物发光技术观察紫杉醇混合胶束的抑瘤效果. 药学学报, 2010, .45(4): 530-534

参考资料

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