张乐帅
电子邮箱：zhangls@suda.edu.cn
个人简介：
张乐帅博士，苏州大学欧洲杯官网、放射医学与辐射防护国家重点实验室教授、博士生导师。2002年获得华东理工大学生物化学学士学位；后由华东理工大学及中国科学院上海生化细胞所（李林院士组）联合培养，参与Wnt细胞信号转导通路研究，于2005年获得硕士学位。同年赴美学习，于美国北卡州立大学（North Carolina State University）从事纳米材料的皮肤安全性研究，包括其透皮吸收能力、对皮肤角质细胞及免疫细胞的功效及安全性评价等，2010年获博士学位。2010年起，于美国食品药物管理局（US FDA）开展糖尿病药物副作用的机制研究及纳米材料的毒性评估，期间还参加药审培训。2012年于美国堪萨斯州立大学（Kansas State University）纳米技术创新中心聘为研究助理教授，从事纳米材料皮肤毒性与食品添加剂肝毒性研究。2014年受聘苏州大学，从事组织工程（细胞三维培养）、纳米/药物毒理学（临床前安全性）及肿瘤免疫学（树突细胞激活、金属佐剂）研究，以及它们在放疗/影像（放疗协同/金属影像剂）中的交叉应用与融合。
研究方向与成果
本研究小组研究方向为纳米毒理学及放射免疫学研究，方向涉及两大部分。一、放射免疫学——生物矿化方法获得免疫佐剂，并创建细胞背包平台，联合放射线治疗肿瘤，并探索作用机制。二、体外替代方法——利用细胞球、微流体/微流控方法探索放射增敏剂/免疫佐剂与肿瘤的体外免疫作用机制。
至今共发表文章50余篇（引用1700余次），其中SCI一作或通讯作者文章40余篇；部分工作被Science Daily等杂志和网站报道；主编专业书籍1本，参编英文书籍2本。主持国家自然科学基金面上在研项目（#31971319、32171403）、教育部留学回国基金；国家自然科学基金面上项目（#81373950、#31771104）与青年基金（#81401511）已结题。
教学经历
负责苏州大学医学部2013级留学生专业选修课《皮肤毒理学与化学品》全英文课程、学校通识课《日常摄影——留住平凡中的不平凡》。
学术服务与任职
苏州市器械不良反应监测专家库成员（2018- ）、中国毒理学会中药毒理专委会青年委员（2018- ）、中国毒理学会纳米毒理专业委员会委员（2016- ）、中国医疗器械行业协会整形美容外科器材专业委员会委员（2018-至今）、美国毒理协会纳米毒理分会执行委员（2012–2013）、美国毒理协会教育委员会执行委员（2011–2015）、江苏省毒理学会卫生毒理与风险评估专委会委员（2020- ）。Toxicology and Industry Health副主编（2016- ）、Journal of Nanobiotechnology副主编（2020- ），Toxicology Research and Applications编委（2021- ）。Toxicological Sciences、Biomaterials、Nanotoxicology等40余种国际毒理、药理及材料相关杂志审稿人，共计审稿200余次。
工业任职
张乐帅博士是美国资格认证毒理学家（Diplomat of the American Board of Toxicology, DABT，2015-）、英国注册毒理学家（UK Register of Toxicologists, UKRT,2018-）、欧洲注册毒理学家（European Register of Toxicologists，ERT,2018-）、中国毒理学会认证毒理学家(Diplomat of Chinese Society of Toxicology, DCST，2021-）。江苏省创新创业首席专家（2017）、中国毒理学会优秀青年科技奖获得者（2020）、苏州工业园区金鸡湖领军人才（2020）、江苏省科技副总（2021）。熟悉国内外的药械妆开发的法律法规，如药物ICH Q/M系列、医疗器械ISO10993/GB16886系列以及MDR注册、OECD化学品安全指南、欧盟及东盟的化妆品成份安全指南。熟练使用PDE、TTC、Cramer结合QSAR方法，为药物的API杂质、清洁验证提供解决方案；委托开展化妆品的安全性评估（CPSR、CPSA）；也为企业、高校、政府的转化项目提供了诸多的咨询与建议。目前兼任苏州苏大卫生与环境技术研究所有限公司的首席科学家及毒理评估中心主任，致力于医疗器械E&L毒理学评估、生物学评价、注册申报相关的框架建设工作。
社会服务
中国民主建国会成员（2014-）、苏州市民建经工委副主任（2017-）、苏州民建苏州大学基层委副主任（2020-）、民主建国会苏州市委委员（2021-）、苏州市政协委员（2021-）；为国家省市撰写了多个政府建议、社情民意以及调研报告。
发表文章
1) Zhang S, Wu Y, Yu J, Ma C, Wang Y, Wang Y, Li L*, Zhang L*. Gadolinium-Bisphosphonate Nanoparticle-Based Low-Dose Radioimmunotherapy for Osteosarcoma. ACS Biomater Sci Eng. 2022 Dec 12;8(12):5329-5337.
2) Xia YN, Zu H, Guo H, Jiang T, Yang S, Yu H, Zhang S, Ding H, Li X, Wang Y, Wang Y*, Zhang L*. Preclinical safety and hepatotoxicity evaluation of biomineralized copper sulfide nanoagents. 2022. International Journal of Nanobiotechnology. 2022 Apr 12;20(1):185.
3) Yu H, Guo H, Ding H, Lin S, Wang Y, Zhang L*. Yong Wang*. Therapeutic Dendritic Cell Vaccines Engineered with Antigen-biomineralized Bi2S3 Nanoparticles for Personalized Tumor Radioimmunotherapy. 2022. Aggregate 3(5), e194.
4) Pang G, Liu Y, Wang Y, Wang Y, Wang F, Zhao J, Zhang L*. Endotoxin contamination in ovalbumin as viewed from a nano-immunotherapy perspective. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021; 10:e1747.
5) Jiang T, Guo H, Xia YN, Liu Y, Chen D, Pang G, Feng Y, Yu H, Wu Y, Zhang S, Wang Y, Wang Y, Wen H, Zhang L*. Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method. Nanomedicine (Lond). 2021;16(17):1487-1504.
6) Wang Q, Zhang QH, Wen HR, Guo HX, Zhang L*, Ma SC. 2020. Study on potential hepatotoxicity of main monomers of Polygonum multiflorum based on liver micro-tissue. Zhongguo Zhong Yao Za Zhi 45(12):2954-2959.
7) Zhang X, Jiang T, Chen D, Wang Q*, Zhang L*. 2020. Three-dimensional liver models: state of the art and their application for hepatotoxicity evaluation. Crit Rev Toxicol 50(4):279-309.
8) Pang G, Chen C, Liu Y, Jiang T, Yu H, Wu Y, Wang Y, Wang FJ*, Liu Z*, Zhang L*. 2019. Bioactive Polysaccharide Nanoparticles Improve Radiation-Induced Abscopal Effect through Manipulation of Dendritic Cells. ACS Appl Mater Interfaces 11(45):42661-42670.
9) Yu H, Yang Y, Jiang T, Zhang X, Zhao Y, Pang G, Feng Y, Zhang S, Wang F, Wang Y, Wang Y, Zhang L*. 2019. Effective Radiotherapy in Tumor Assisted by Ganoderma lucidum Polysaccharide-Conjugated Bismuth Sulfide Nanoparticles through Radiosensitization and Dendritic Cell Activation. ACS Appl Mater Interfaces. 11(31):27536-27547.
10) Cao Y, Huang H, Chen L, Du H, Cui J, Zhang L*, Lee B, Cao Q*. 2019. Enhanced Lysosomal Escape of pH-Responsive PEI-Betaine Functionalized Carbon Nanotube for the Co-delivery of Survivin siRNA and Doxorubicin. ACS Applied Materials & Interfaces 11(10):9763-9776.
11) Pang G, Zhang S, Yu H, Wu Y, Jiang T, Wang F*, Wang Y*, Zhang L*. 2019. Immunoactive Astragalus Polysaccharide Functionalized Gold Nanocomposites Promote Dendritic Cell Stimulation and Anti-tumor Effect with Elicited Memory T-cell Responses. Nanomedicine 14(10):1291-1306.
12) Zhang S, Pang G, Chen C, Qin J, Yu H, Liu Y, Zhang X, Song G, Zhao J, Wang F*, Wang Y*, Zhang L*. 2019. Effective Cancer Immunotherapy by Ganoderma Lucidum Polysaccharide-Gold Nanocomposites through Dendritic Cell Activation and Memory T cell Response. Carbohydrate Polymer 205:192-202.
13) Zhang L*, Monteiro-Riviere NA Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes. 2018. Cutaneous and Ocular Toxicology. 2018 Sep 28:1-29.
14) Song ZT, Zhang L, Fan LQ, Kong JW, Mao JH, Zhao J, Wang FJ. 2018. Enhanced anticancer effect of MAP30-S3 by cyclosproin A through endosomal escape. Anti-cancer Drugs 29(8):736-747.
15) Pan G, Wang F*, Zhang L*. 2018. Direct Killing or Immunoregulatory Effects of Natural Polysaccharides in Cancer Treatment. Carbohydrate Polymer 195: 243–256.
16) Liu Y, Yu H, Zhang X, Wang Y, Zhao J, Shi H, Li R, Wang Y*, Zhang L*. 2018. The Protective Role of Autophagy in Nephrotoxicity Induced by Bismuth Nanoparticles Through AMPK/mTOR Pathway. Nanotoxicology 6:1-16.
17) Zhang X, Yang L, Liu Y, Song Z, Zhao J, Chen D, Yu Huan, Li R, Wang Y, Yang K, Chen Y, Xia M, Zhang L*. 2018. Detection of Nanocarrier Potentiation on Drug Induced Phospholipidosis in Cultured Cells and Primary Hepatocyte Spheroids by High Content Imaging and Analysis. Toxicology and Applied Pharmacology 348: 54–66.
18) Chen D, Yang L, Chen X, Zhang X, Liu Y, Guo Z*, Zhang L*. 2018. Automated contour analysis of multi-cellular spheroids spreading through high content imaging. Physical Biology 24: 15:026006
19) Liu Y, Shen C, Zhang X, Yu H, Wang F, Wang Y*, Zhang L*. 2018. Exposure and Nephrotoxicity Concern of Bismuth with the Occurrence of Autophagy. Toxicology and Industrial Health 34:188–199
20) Li J, He X, Zou Y, Chen D, Yang L, Rao J, Chen H, Chan M CW, Guo Z*, Zhang L*, Chen C. 2017. Mitochondria-Targeted Platinum(II) Complex: Dual Inhibitory Activities on Tumor Cell Proliferation and Migration/Invasion via Intracellular Trafficking of β-catenin. Metallomics 9:726-733.
21) Liu Y, Zhuang J, Zhang X, Le C, Zhu N, Yang L, Wang Y, Chen T, Wang Y*, Zhang L* 2017. Autophagy Associated Cytotoxicity and Cellular Uptake Mechanisms of Bismuth Nanoparticles in Human Kidney Cells. Toxicology Letters 275: 39-48.
22) Chen D, Monteiro-Riviere NA, Zhang L*. 2017. Intracellular imaging of quantum dots, gold, and iron oxide nanoparticles with associated endocytic pathways. WIREs Nanomedicine and Nanobiotechnology 9(2).
23) Yang L, Zhong X, Li Q, Zhang X, Wang Y, Yang K, Zhang L*. 2017. From the Cover: Potentiation of Drug-Induced Phospholipidosis In Vitro through PEGlyated Graphene Oxide as the Nanocarrier. Toxicological Sciences 156:39–53.
24) Wang Y, Liu Y, Wu Y, Shen J, Lv L, Li L, Yang L, Zeng J, Wang Y, Zhang L*, Li Z*, Gao M*, Chai Z. 2016. BSA-Mediated Synthesis of Bismuth Sulfide Nanotheranostic Agents for Tumor Multimodal Imaging and Thermoradiotherapy. Advanced Functional Materials 26: 5335–5344.
25) Zhu N, Lv X, Wang Y, Li J, Liu Y, Lu W, Yang L, Zhao J, Wang F, Zhang L*. 2016. Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendritic cells. International Journal of Biological Macromolecules 93:940–951.
26) Wang Y*, Zhu L, Wang Y, Li L, Lu Y, Shen L*, Zhang L*. 2016. Ultrasensitive GSH-Responsive Ditelluride-Containing Poly(ether-urethane) Nanoparticles for Controlled Drug Release. ACS Applied Materials & Interfaces 8: 35106–35113.
27) Lv X, Chen D, Yang L, Zhu N, Li J, Zhao J, Hu Z, Wang F*, Zhang L*. 2016. Comparative Studies on the Immunoregulatory Effects of Three Polysaccharides Using High Content Imaging System. International Journal of Biological Macromolecules 86:28–42.
28) Zhang L, Koci J, Brett J, Riviere JE, Monteiro-Riviere NA. 2015. Safety Assessment of Potential Food Ingredients in Canine Hepatocytes. Food and Chemical Toxicology 78:105–15.
29) Zhang L, Shea KI, Xu L, Stewart S, Zhang J, Rouse RL. 2014. Autophagy in pancreatic acinar cells in caerulein treated mice: Immunolocalization of related proteins and their potential as markers of pancreatitis. Toxicologic Pathology 42, 435–457.
30) Zhang L, Monteiro-Riviere NA. 2013. Use of confocal microscopy for nanoparticle drug delivery through skin. Journal of Biomedical Optics. 18(6):061214
31) Zhang L, McMahon Tobin GA, Rouse RL. 2012. Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line. Toxicology and Applied Pharmacology 264: 274–283.
32) Zhang L, Bäumer W, Monteiro-Riviere NA. 2011. Cellular uptake mechanisms and toxicity of quantum dots in dendritic cells. Nanomedicine. 6: 777–791.
33) Zhang L, Monteiro-Riviere NA. 2010. Lectins modulate multi-walled carbon nanotubes cellular uptake in human epidermal keratinocytes. Toxicology In Vitro 24: 546–555.
34) Zhang L, Yang J, Barron AR, Monteiro-Riviere NA. 2009. Endocytic mechanisms and toxicity of a functionalized fullerene in human cells. Toxicology Letters 191: 149–157.
35) Zhang L, Monteiro-Riviere NA. 2009. Mechanisms of quantum dot nanoparticle cellular uptake. Toxicological Sciences. 110: 138–155.
36) Zhang L, Monteiro-Riviere NA. 2008. Assessment of quantum dot penetration into intact, tape-stripped, abraded and flexed rat skin. Skin Pharmacology and Physiology 21:166 –180.
37) Zhang L, Yu WW, Colvin VL, Monteiro-Riviere NA. 2008. Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes. Toxicology and Applied Pharmacology 228:200–211.
38) Zhang L, Zeng L, Barron AR, Monteiro-Riviere NA. 2007. Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes. International Journal of Toxicology 26:103–113.
（更新于2023年3月31日）