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刘方雪 博士生导师    

钱锋博士本科、硕士毕业于清华大学材料科学与工程系。 2003年于美国Case Western Reserve University获得生物医学工程博士学位。2003年4月起就职于美国制药企业Bristol-Myers Squibb Company(百时美-施贵宝公司),历任研究员(Research Investigator),资深研究员(Senior Research Investigator),和主任科学家(Principal Scientist),从事药剂学和药物成品的科研,开发,项目管理,和学术界合作等工作。2012年入选中组部千人计划(青年类),加入清华大学医学院药学系(现药学院),从事药物制剂和给药系统研究工作。 在美国工作期间,钱锋博士的工作涉及20多个新药(包括化学和生物药物)的研发,其中包括主持多项一期到三期的新药临床药剂开发,以及多项新药产品的项目管理工作。同时,钱锋博士负责开发和评估新型药剂技术平台,支持新技术在产品上的应用。在新型药物制剂领域,钱锋博士已申请10多项美国/中国专利,成功将多个创新候选药物带入不同阶段的临床试验。钱锋博士已发表~50余篇学术论文,并应邀在众多药剂学国际会议,包括American Association of Pharmaceutical Scientists, American Chemical Society 等会议上做学术报告。钱锋博士是Molecular Pharmaceutics, Journal of Pharmaceutical Science, AAPS PharmSciTech 等期刊的Editorial Advisory Board 成员,中国药学会纳米药物专业委员会委员。


研究方向

1) 针对癌症的药物递送:本实验室致力于设计和评估针对胰腺癌等癌症的新型药物递送体系和技术。我们的主要研究兴趣是针对或者利用癌症的生物学特征(肿瘤微环境、代谢等)进行合理的药物递送体系设计,以期获得具有更好癌症治疗效果,并可临床和工业转化的新型癌症治疗药物,以满足亟待解决的临床需求。


2)物理药剂学及先进制剂技术: 当今进入临床开发的候选新药约一半为小分子化学药物,另一半则为以蛋白为代表的生物药。开发化学小分子新药制剂面临的最主要的难题是,大多数药物(~70%)为难溶性药物,传统制剂手段往往无法获得足够的生物利用度。针对此问题,本课题组围绕新型制剂(特别是非晶药物制剂,纳米晶体制剂等)的物理化学机理,体内外药物制剂的表现,具备全新药学特性的新型制剂技术,等领域进行深入研究。在蛋白药物领域,本课题组的研究兴趣在高浓度蛋白溶液(特别是单抗药物)的粘度和物理稳定性调控,以及辅料-蛋白,蛋白-蛋白之间的相互作用。以上研究的根本目的是为未来的新药产品开发提供理论依据和技术手段。在这些领域,本课题组和包括美国百时美-施贵宝(Bristol-Myers Squibb), 强生(Johnson & Johnson),德国拜耳(Bayer), 等跨国制药企业建立了科研合作关系。 0


代表性论文


癌症药物递送方向


  1. Kong C; Li Y; Liu Z; Ye J; Wang Z; Zhang L; Kong W.; Liu H.; Liu C.; Pang H.; Hu Z.; Gao J.; and Qian, F*, Targeting the Oncogene KRAS Mutant Pancreatic Cancer by Synergistic Blocking of Lysosomal Acidification and Rapid Drug Release, ACS Nano, DOI: 10.1021/acsnano.8b08246, Publication Date (Web): March 26, 2019
  2. Liu H; Sun M; Liu Z; Kong C; Kong W; Ye J; Gong J; Huang D; Qian, F.*, KRAS-enhanced macropinocytosis and reduced FcRn-mediated recycling sensitize pancreatic cancer to albumin-conjugated drugs, Journal of Controlled Release, Vol 296, 28 February 2019, Pages 40-53 
  3. Zhang L, Liu Z, Kong C, Liu C, Yang K, Chen H, Huang J, Qian F*., Improving Drug Delivery of Micellar Paclitaxel against Non‐Small Cell Lung Cancer by Coloading Itraconazole as a Micelle Stabilizer and a Tumor Vascular Manipulator, Small, 2018, 14, 1802112,DOI: 10.1002/smll.201802112
  4. Zhang L, Zhen Chen, Kuan Yang, Chun Liu, Jinming Gao, and Qian, F*.; β-Lapachone and Paclitaxel Combination Micelles with Improved Drug Encapsulation and Therapeutic Synergy as Novel Nanotherapeutics for NQO1-Targeted Cancer Therapy, Mol.Pharmaceutics, 2015, 12 (11), pp 3999–4010



提高难溶药物的口服生物利用度


  1. Chen H.; Zhang X.; Cheng Y.; Qian,F*, Preparation of smectic itraconazole nanoparticles with tunable periodic order using microfluidics based anti-solvent precipitation, CrystEngComm, 2019, 21, 2362-2372
  2. Chen, Y.; Pui, Y.; Chen, H.; Wang, S; Serno, P.; Tonnis, W.; Chen, L.; Qian F.*, Polymer mediated drug supersaturation controlled by drug-polymer interactions persisting in aqueous environment, Mol. Pharmaceutics, 2019, 16 (1), pp 205–213
  3. Wang S,; Liu C,; Chen Y.; Zhu A.; Qian F*, Aggregation of Hydroxypropyl Methylcellulose Acetate Succinate under Its Dissolving pH and the Impact on Drug Supersaturation, Mol. Pharmaceutics, 2018, 15, 4643−4653
  4. Chen Z., Yang K., Huang C., Zhu A., Yu L., Qian F.*, Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions, Pharmaceutical Research (2018) 35: 38. https://doi.org/10.1007/s11095-018-2345-1
  5. Chen, Z.; Liu, CY.; Zhang, L.; Qian, F.*; Dissolution Characteristics of Fast-Crystallizing β-Lapachone within Different Semicrystalline Microstructures of Polyethylene Glycol or Poly(ethylene oxide)–Poly(propylene oxide)–Poly(ethylene oxide) Triblock Copolymer, Cryst. Growth Des., 2016, 16, 5367-5376
  6. Chen YJ.; Wang S; Wang S.; Liu C.; Su, C.; Hageman, M.; Hussain, M.; Haskell. R.; Stefanski K.;  Qian, F*.; Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction, Pharmaceutical Research, 2016, 33(10), 2445-2458.
  7. Liu C, Chen Z, ChenYJ.; Lu J’; Li Y.; Wang S.; Wu G.; Qian F* Improving Oral Bioavailability of Sorafenib by Optimizing the “Spring” and “Parachute” Based on Molecular Interaction Mechanisms, Mol. Pharmaceutic, 2016, 13 (2), pp 599–608
  8. Chen, Z.; Liu,ZS.; Qian, F.*; Crystallization of Bifonazole and Acetaminophen within the Matrix of Semicrystalline, PEO-PPO-PEO Triblock Copolymers, Mol. Pharmaceutics, 2015 Feb 21;12(2):590-9.
  9. Chen YJ.; Liu CY.; Chen.Z.; Su, C.; Hageman, M.; Hussain, M.; Haskell. R.; Stefanski K.; Qian, F*.; Drug-polymer-water Interaction and its Implication to the Dissolution Performance of Amorphous Solid Dispersions, Mol. Pharmaceutics, 2015 Feb 12;12(2):576-89.


高浓度蛋白溶液


  1. Wang S, Zhang X, Wu G, Tian Z, Qian F.*; Optimization of high-concentration endostatin formulation: Harmonization of excipients' contributions on colloidal and conformational stabilities., Int J Pharm. 2017 Sep 15;530(1-2):173-186. doi: 10.1016/j.ijpharm.2017.07.057. Epub 2017 Jul 26.
  2. Wu G, Wang Co-First S, Tian Z, Zhang N, Sheng H, Dai W, Qian F.*, Elucidating the Weak Protein-Protein Interaction Mechanisms behind the Liquid-Liquid Phase Separation of a mAb Solution by Different Types of Additives. Eur J. Pharm. Biopharm. 2017 Jul 25. pii: S0939-6411(17)30571-4. doi: 10.1016/j.ejpb.2017.07.012.
  3. Wang, S.; Wu, G.; Zhang, X.; Tian, Z.; Zhang, N.; Hu, T.; Dai.; W.; Qian F*, Stabilizing two IgG1 monoclonal antibodies by surfactants: Balance between aggregation prevention and structure perturbation, Euro. J. Pharm. Biopharm., Volume 114, May 2017, Pages 263–277
  4. Wang S, Zhang N, Hu T, Dai W, Feng X, Zhang X, and Qian F*.; Viscosity-Lowering Effect of Amino Acids and Salts on Highly Concentrated Solutions of Two IgG1 Monoclonal Antibodies, Mol. Pharmaceutics, 2015, 12 (12), pp 4478–4487