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于海军

于海军.png

教育经历

2001.09 –2006.12        中科院长春应用化学研究所,博士,生物医用高分子

1997.09 –2001.07        内蒙古大学化学化工学院,学士,化学


工作经历

1. 2017.01-现在,特聘研究员,烟台药物研究所

2. 2016.10-现在,研究员,中科院上海药物研究所

3. 2012.05~2016.09,中科院上海药物研究所,副研究员

4. 2011.02~2012.04,日本东北大学,博士后(助手)

5. 2009.02~2011.01,美国德州大学西南医学中心癌症中心,博士后

6. 2007.02-2009.01,德国慕尼黑大学药学系,博士后

  

研究方向

抗肿瘤创新药物与智能纳米药物递送系统


专家类别

研究员,优青 


科研成果

近五年来在抗肿瘤创新药物与智能纳米药物递送系统的基础研究与临床转化方面取得了突出成绩:

(1)设计并构建了胞内酸环境和近红外光双重响应纳米载药系统,发现光热效应可降解胞外基质,克服肿瘤生理屏障,显著改善化疗效果;发现胞内酸激活的光动力效应可有效降解溶酶体膜,逃避胞内“离子陷阱”,大幅改善耐药肿瘤化疗效果。上述发现有望为研发更加有效的抗肿瘤纳米药物提供新思路。

(2)利用快速酸响应纳米载药系统证明AmB和siRNA共输送可有效克服“内涵体逃逸”屏障,显著提高siRNA递送效率;构建酸响应长循环siRNA递送系统,发现活体水平阻断MDM2信号通路可有效抑制非小细胞肺癌生长,较早地证实MDM2可作为潜在靶点用于肿瘤RNA分子靶向治疗。上述发现为设计、构建新型高效非病毒基因递送系统奠定了良好基础。

(3)设计并构建快速酸响应siRNA和化疗药物共递送系统,发现阻断NF-kB信号通路可有效抑制癌细胞转移;发现近红外光响应主客体纳米载药系统的光热效应可诱导内涵体降解,促进siRNA胞内转运,实现时空可控药物释放,RAN干扰和化疗协同增效,有效抑制肿瘤生长和转移,有望为下一步发展更加安全高效的抗肿瘤转移纳米载药系统提供有价值参考。

 

获奖及荣誉

1. 2017年,科技部中青年科技创新领军人才

2. 2017年,中国药学会-赛诺菲青年生物药物奖

3. 2016年,国家基金委优秀青年基金

4. 2016年,科技部重点领域创新团队骨干成员

5. 2015年,国家自然科学基金委创新研究群体成员

6. 2015年,中国药学会科学技术奖一等奖(排名第四)

7. 2014年,中国药学会-中恒青年药剂学奖

8. 2013年,赛诺菲-上海生科院优秀青年人才奖

9. 2013年,中科院青年人才促进会

10. 2013年,上海市药学科技一等奖(排名第四)

 

主持国家自然科学基金“优青”、面上项目和科技部 “973”课题等多项国家级科研项目,并作为主要学术骨干参加国家自然科学基金创新研究群体和重点项目。近5年共发表SCI论文60篇,其中第一/通讯作者论文25篇(IF>7的16篇),包括Nano Letters(IF=13.779), ACS Nano(IF=13.334),Adv Funct Mater(IF=11.382),Biomaterials (IF=8.387),Small(IF=8.315),Theranostics(IF=8.854)和Nanoscale(IF=7.760)等国际权威期刊。所发论文他引共1500余次,单篇最高他引90次。申报中国发明专利10项(授权3项)。获得创新药物临床批件1项,完成临床前研究申报临床试验1项。在国内外重要学术会议作邀请或分会报告20余次。

 

代表论著

1.    Dangge Wang, Tingting Wang, Jianping Liu, Haijun Yu,* Shi Jiao, Bing Feng, Fangyuan Zhou, Yuanlei Fu, Qi Yin, Pengcheng Zhang, Zhiwen Zhang, Zhaocai Zhou, Yaping Li,* Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade-Enhanced Cancer Photodynamic Immunotherapy. Nano Letters 2016, 16, 5503-5513.

2.      Tingting Wang, Dangge Wang, Haijun Yu*, Mingwei Wang, Jianping Liu, Bing Feng, Fangyuan Zhou, Qi Yin, Zhiwen Zhang, Yaping Li* Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/ Chemotherapy of the Drug Resistant Tumor. ACS Nano 2016, 10, 3496-3508.

3.      Bing Feng, Fangyuan Zhou, Zhiai Xu, Tingting Wang, Dangge Wang, Jianping Liu, Qi Yin, Zhiwen Zhang, Haijun Yu*, Yaping Li*. Versatile Prodrug Nanoparticles for Acid-Triggered Precise Imaging and Organelle-Specific Combination Cancer Therapy. Adv. Funct. Mater. 2016, 26, 7431-7442.

4.      Haijun Yu*, Zhirui Cui, Pengcheng Yu, Chengyue Guo, Bing Feng, Tongying Jiang, Siling Wang, Qi Yin, Dafang Zhong, Xiangliang Yang, Zhiwen Zhang, Yaping Li*. pH and near-infrared light-responsive micelles with hyperthermia-triggered tumor penetration and cytoplasm drug release reverse doxorubicin resistance in breast cancer. Adv. Funct. Mater. (Front Cover) 2015, 25, 2489-2500.

5.      Haijun Yu, Yonglong Zou, Yiguang Wang, Xiaonan Huang, Gang Huang, Baran D. Sumer, David A. Boothman, Jinming Gao*. Overcoming Endosomal Barrier by Amphotericin B-loaded Dual pH-Responsive PDMA-b-PDPA Micelleplexes for siRNA Delivery. ACS Nano 2011, 5, 9246-9255.

6.      Haijun Yu, Junqiang Wang*, Xuetao Shi, Dmitri V. Louzguine-Luzgin, Hongkai Wu*, John H. Perepezko* Ductile Biodegradable Mg-based Metallic Glasses with Excellent Biocompatibility. Adv. Funct. Mater. 2013, 23, 4793-4800.

7.      Qiang Feng, Jianping Liu, Xuanyu Li, Jiashu Sun,* Xinghua Shi, Haijun Yu,* Yaping Li, and Xingyu Jiang* One-Step Microfluidic Synthesis of Nanocomplex with Tunable Rigidity and Acid-Switchable Surface Charge for Overcoming Drug Resistance. Small 2017, DOI:10.1002/smll.201603109.

8.      Fangyuan Zhou, Bing Feng, Haijun Yu*, Dangge Wang, Tingting Wang, Jianping Liu, Qingshuo Meng, Siling Wang,*, Pengcheng Zhang, Zhiwen Zhang, Yaping Li*, Cisplatin Prodrug-Conjugated Gold Nanocluster: A Theranostic Platform for Treatment of Metastatic Breast Cancer. Theranostics 2016, 6, 679-687.

9.      Dangge Wang#, Tingting Wang#, Zhiai Xu, Haijun Yu*, Bing Feng, Junying Zhang, Chengyue Guo, Qi Yin, Zhiwen Zhang, Yaping Li* Cooperative Treatment of Metastatic Breast Cancer Using Host-Guest Nanoplatform Loading Docetaxel and siRNA. Small 2016, 12, 488-498.

10.   Haijun Yu*, Chengyue Guo, Xianzhi Chen, Bing Feng, Jianping Liu, Tingting Wang, Dangge Wang, Zhirui Cui, Qi Yin, Zhiwen Zhang, Yaping Li* Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer. Theranostics 2016, 6, 14-27.

11.   Chongsheng Guo, Haijun Yu*, Bing Feng, Weidong Gao, Mei Yan, Zhiwen Zhang, Yaping Li*, Shaoqing Liu*. Highly efficient ablation of metastatic breast cancer using ammonium-tungsten-bronze nanocube as a novel 1064 nm-laser-driven photothermal agent. Biomaterials 2015, 52, 407-416.

12.  Dangge Wang, Zhiai Xu, Haijun Yu*, Xianzhi Chen, Bing Feng, Zhirui Cui, Bin Lin,Qi Yin, Zhiwen Zhang, Chunying Chen, Jun Wang, Wen Zhang, Yaping Li. Treatment of metastatic breast cancer by combination of chemotherapy and photothermal ablation using doxorubicin-loaded DNA wrapped gold nanorods. Biomaterials 2014, 35, 8374-8384. (2014年7-9月最高下载量TOP25)

13.   Haijun Yu, Yonglong Zou, Lei Jiang, Qi Yin, Xinyu He, Lingli Chen, Zhiwen Zhang,Wangwen Gu, Yaping Li*. Induction of Apoptosis in Non-Small Cell Lung Cancer by Downregulation of MDM2 Using pH-Responsive PMPC-b-PDPA/siRNA Complex Nanoparticles. Biomaterials 2013, 34, 2738-2747.

14.   Lijuan Zeng#, Lili Zou#, Haijun Yu#, Xinyu He, Haiqiang Cao, Zhiwen Zhang, * Qi Yin, Pengcheng Zhang, Wangwen Gu, Lingli Chen, and Yaping Li. Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration. Adv. Funct. Mater. 2016, 26, 4201-4212.

15.   Xinyu He#, Haijun Yu#, Xiaoyue Bao, Haiqiang Cao, Qi Yin, Zhiwen Zhang*, Yaping Li*. pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer. Adv. Healthcare Mater. 2016, 5,439-448.

16.   Bing Feng, Zhiai Xu, Fangyuan Zhou, Haijun Yu*, Qianqian Sun, Dangge Wang, Zhaohui Tang, Haiyang Yu, Qi Yin, Zhiwen Zhang, Yaping Li,* Polypeptide-Wrapped Gold Nanorods as a Dual-modal Nanoplatform for Combinational Photothermal and Chemo-therapy of Metastatic Breast Cancer. Nanoscale 2015, 7, 14854-14864 (2015 Hot Papers in Nanoscale).

17.   Pengcheng Yu, Haijun Yu*, Chengyue Guo, Zhirui Cui, Xianzhi Chen, Qi Yin, Zhiwen Zhang, Xiangliang Yang, Yaping Li*. Reversal of Doxorubicin Resistance in Breast Cancer by Mitochondria-Targeted pH-Responsive Micelles. Acta Biomater 2015,14,115-124.

18.   Haijun Yu, Zhiai Xu, Xianzhi Chen, Qi Yin, Zhiwen Zhang, Yaping Li,* Reversing Lung Cancer Multidrug Resistance Via Dual pH-Responsive Micelleplexes Mediated siRNA and Paclitaxel Co-Delivery. Macromol. Biosci. 2013, 14, 100-109. (Most Accessed article in 9/2013)

19.   Bing Feng, Fangyuan Zhou, Dangge Wang, Haijun Yu*, Yaping Li. Gold Nanomaterials for Treatment of Metastatic Cancer (review article). Sci. China Chem. 2016, 59, 984-990.

20.   Haijun Yu, Zhiai Xu, Dangge Wang, Xianzhi Chen, Zhiwen Zhang, Yaping Li,*Intracellular pH-Activatable PEG-b-PDPA Wormlike Micelles for Hydrophobic Drug Delivery. Polym. Chem., 2013, 4, 5052-5055.

21.   Chongshen Guo, Shu Yin*, Haijun Yu*, Shaoqin Liu*, Qiang Dong, Takehiro Goto, Zhiwen Zhang, Yaping Li*, Tsugio Sato. Photothermal Ablation Cancer Therapy using Homogeneous CsxWO3 Nanorods with Broad Near-Infra-Red Absorption. Nanoscale 2013, 5, 6469-6478.

22.   Zhiwen Zhang, Zeying Liu, Li Ma, Shijun Jiang, Yixin Wang, Haijun Yu*, Qi Yin, Jingbin Cui, Yaping Li*. Reversal of Multidrug Resistance by Mitochondrial Targeted Self-assembled Nanocarrier based on Stearylamine. Molecular Pharmaceutics, 2013, 10, 2426-2434.

23.   Haijun Yu*, Yu Nie, Christian Dohmen, Yunqiu Li, Ernst Wagner. Epidermal Growth Factor–PEG Functionalized PAMAM-Pentaethylenehexamine Dendron for Targeted Gene Delivery Produced by Click Chemistry. Biomacromol. 2011, 12, 2039-2047.

24.   Jianping Liu, Tingting Wang, Dangge Wang, Anjie Dong*, Yaping Li, Haijun Yu*, Smart Nanoparticles for Therapy of the Drug-Resistant Tumors by Overcoming the Pathophysiological Barriers. Acta Pharmacologica Sinica. 2017, 38,1-8.

25.   Haijun Yu, Chao Deng, Huayu Tian, Tiancheng Lu, Xuesi Chen, Xiabin Jing*. Chemo-Physical and Biological Evaluation of Poly(L-lysine) Grafted Chitosan Copolymers Used for Highly Efficient Gene Delivery. Macromol. Biosci. 2011, 10. 352-361.


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