研究生教育

        教育部长江学者特聘教授、浙江大学求是特聘教授、生物纳米工程中心主任。于91、95年分别获浙江大学理学学士和博士学位，获首届《全国优博论文奖》；02年获加拿大McMaster University工学博士学位。02年起任美国怀俄明大学 （University of Wyoming）助理教授，07年被破格晋升为tenure的副教授，08年受邀回国任浙江大学求是学者教授和生物纳米工程中心主任。主要从事功能高分子合成及其应用于纳米药物的研究。在美国执教期间主持美国国家科学基金等项目10余项, 回国后主持973前期及基金委重大项目课题和重点项目、国家重大科学研究计划项目(首席科学家)等。在Nature Nanotechnology、Nature Biomedical Engineering、J. Am. Chem. Soc.、Angew. Chem. Int. Ed.和Adv. Mater.等国际著名学术期刊上发表SCI论文280余篇，H-因子60，出版RSC和Wiley著作各1部，获10余项中美专利，工作三次被美国Chemical& Engineering News报道。

        兼美国化学会Industrial and Engineering Chemistry Research（IECR）副主编, 中国药学会纳米药物专业委员会副主任委员、中国医药生物技术协会生物纳米技术分会副主任委员及多个期刊编委，入选美国Fellow of American Institute of Biological and Medical Engineering (2018)。2015年起连续入选中国高被引学者材料科学榜。

研究方向

一、用于癌症治疗的纳米药物载体的设计与合成

        研究方向包括新型纳米载体的设计与合成、靶向纳米药物的制备、纳米药物的体外毒性及机理、纳米药物在细胞内的传输过程、纳米药物的体内（裸鼠）的靶向性能和药效（如抗癌性能）、临床实验等。 目前的工作之一是研制能够靶向肿瘤细胞器的纳米药物载体，从而将药物直接输送到它们的作用靶点，使药物同时避开各种抗药机制, 提高药物的药效。本纳米药物的优点是药物直接到达其作用靶点、克服多种抗药机制。

二、高效非病毒基因输送载体的设计

        通过基因疗法 (Gene Therapy), 即将目标基因导入靶细胞的核内以表达所需蛋白从而达到治疗之目的，可以改变癌细胞来降低其包括细胞核内抗药机制在内的各种抗药性。基因疗法的瓶颈是基因的靶向传送。病毒类载体介导的基因传送具有高的转染率和良好的靶向性，但多个临床实验发现病毒类载体容易引起人体复杂的免疫反应而导致病人死亡并会致癌。阳离子型聚合物也可用做基因传送的载体。它具有毒性低，不会引起机体的过度免疫反应的优点，但它的缺点是基因表达效率低。有鉴于此，我们目前的研究工作是研制能够模拟病毒体的聚合物/DNA的自组装体作为DNA的高效输送载体。

三、用于癌症早期诊断的高灵敏性磁共振成像（MRI）造影剂的设计和开发

        肿瘤早期发现是治愈癌症的关键。例如，早期肾癌的五年存活率可达到99％，而二期以上的病人五年存活率只有16％。但是，许多肿瘤在早期并没有症状，因而很难被发现，而被发现时已到晚期或已发生转移。磁共振成像(MRI)在临床中被越来越广泛地用于癌症的诊断，但它的灵敏性还不够高，误诊率比较高且造成许多不必要的组织活切诊断。MRI的灵敏性取决于造影剂。常用MRI造影剂是稀土金属离子Gd3＋的小分子或大分子络合物。研究发现，将Gd3＋络合到大分子载体上，能显著提高MRI的灵敏性，但它们的灵敏性还有待进一步提高。

        我们致力于研制种癌组织靶向和肿瘤特异性激活型造影剂载体，该载体同时还能显著提高核磁共振中肿瘤部位的对比度。已与浙大附属邵逸夫医院放射科的胡红杰主任医师开展合作，以期获得能应用于临床的高灵敏性MRI造影剂，用于肿瘤的早期诊断。

四、树枝状大分子的高效合成

        树枝状大分子因其精确的三维纳米分子结构，被广泛作为纳米技术平台应用于医药领域，如作为药物和基因运输载体。然而，传统的树枝状大分子合成方法复杂，需要保护/去保护及繁琐的纯化过程限制了树枝状大分子的大规模应用。我们发明了一种聚酯树枝状大分子的高效合成方法，即采用在化学反应性上不对称的单体和功能基团之间的点击化学反应，通过“不对称单体对”间的简单交替“粘贴”的方法合成聚酯树枝状大分子。该方法合成步骤简单，目标产物为唯一的大分子，因而纯化过程极为简便，可广泛用于生物可降解聚酯的大规模生产应用，如作为药物传输载体。

五、前药为多功能纳米载体

        大多数抗癌药物在水中的溶解性差，且有些药物分子（如喜树碱的内酯环）在血液中不稳定，极大限制了抗癌药物的临床应用。药物输送技术是解决上述问题的有效途径之一。此外，通过药物载体可延长药物的半衰期，且能通过肿瘤组织的EPR效应提高药物在肿瘤部位的聚集，提高药物的靶向性并降低其毒副作用。然而，目前药物输送体系亟需解决的问题是载药能力太低。如在纳米颗粒载体或脂质体内，载药量一般不超过10%，且载药体系不稳定，在血液中存在突释现象，导致药物的生物利用度低且可能导致系统生物毒性。低载药量也造成治疗时需使用大量的医用载体辅料，对机体产生毒副作用。我们利用药物分子本身的疏水性或亲水性，以药物分子作为疏水或亲水部分，通过与亲水基团或疏水基团的共价结合来制备自乳化药物前药。该前药溶于缓冲液中即形成纳米囊泡或纳米颗粒，且既是原药的载体，又可携带其他药物，并具有肿瘤靶向功能，因此成为多功能的纳米抗癌药物。

研究项目基金

在美国工作期间获得的资助(2002.11-2008.3)

美国国家科学基金资助项目（NSF-CBET 0352812): 模板-可控活性聚合自组装类高分子, 10/15/2003-03/31/2006, $99,943，负责人

美国国家科学基金资助项目（NSF-CBET 0401982): 抑制抗癌药物抗药性纳米颗粒的设计，06/01/2004-05/30/2007, $317,024, 负责人

美国国家科学基金资助项目（NSF-CBET 0650608): 自组装聚合物的合成与表征, $149,976.00, 06/01/2007-05/31/2009，负责人

美国国家科学基金资助项目（NSF-DMR 0705298): 用于基因传送的可降解聚合物的设计, 07/15/2007-06/14/2010，$375,000, 负责人

美国国家科学基金资助项目（NSF-CBET 0753109): 癌细胞核靶向的纳米颗粒用于癌症化疗的研究，06/01/2008-05/30/2011，$240,138, 负责人

美国癌症协会研究学者基金（RSG-06-118-01-CDD): 向癌细胞内快速药物输送的纳米颗粒用于子宫癌的研究，06/18/06-06/17/09, $ 690,000, 负责人

美国乳腺癌症Concept型基金（DOD Breast Cancer Concept Award BC062422): 癌细胞核靶向药物键合物用于乳腺癌的研究, 09/01/2007-08/30/2008, $107,250, 负责人

美国乳腺癌Idea型基金（DOD Breast Cancer Idea Award BC083821)：癌细胞核靶向的药键合物用于乳腺癌的研究,12/01/2008-11/30/2011，$528,939,负责人

怀俄明州（State of Wyoming）资助项目: CO2分离高分子材料, 负责人

06/01/2004-05/30/2006, $530,000 (direct cost)

06/01/2006-05/30/2008, $388,000 (direct cost)

美国国家科学基金资助项目（NSF-CTS44313): 聚己内酯胶束纳米颗粒的分离，09/15/2006 -08/31/2007, $119,999, 子负责人

美国交通部北方中心（Sun Grant Regional Competitive Grant Program): 新型可回收酶纳米颗粒用于纤维素水解的研究, 07/01/2007-06/30/2011, $483,782, 子负责人  

回国后在浙江大学工作期间获得的资助

1.国家自然科学基金委面上基金20974096：癌细胞核逐级靶向的聚合物－药物键合物作为癌靶向药物载体的研究，2009.1-2011.12，34万RMB，负责人

2.973 计划前期研究专项2009CB526403：利用肿瘤细胞核靶向药物输送克服肿瘤抗药性的研究，2009.4.-2011.4，66万RMB，主持

3.国家自然科学基金委重大项目：课题2：新型拓扑高分子的高效合成21090352，2011.1-2014.12，课题二主持人，260万RMB

4.国家自然科学基金委重大项目：课题1：高分子纳米载体结构与体内药物输送特定过程的相关性研究 51390481，2014.1-2018.12，课题二子负责人，总经费590万，本人负责290万RMB

5.科技部国家重大科学研究计划纳米专项2014CB931900：核酸药物高效纳米载药系统的研究，2014.1-2018.12，首席科学家及课题一负责人，总经费1490万.

6.国家自然科学基金委-广东省联合基金：作用于肿瘤微环境的无毒抗肿瘤高分子的设计，2016.1-2020.12，主持，290万

7.国家自然科学基金委重点项目51833008：酶响应电荷反转聚合物的设计与高疗效抗肿瘤纳米药物的构建，2019.1-2023.12，主持，300万元.

部分同行评审的科技期刊和专著论文 : （*为通讯联系人; Total 298 papers, Total Citations 11,392, H-index 62)

Edited Books and Book Chapters

1)Y.Shen (Editor-in-Chief) Materials Research Series: Biomaterials Engineering, Nature-Springer Publisher (totally 26 volume, 1 volumn in press, 3 volumes to be published in 2019)

2) Y.L. Zhao and Y. Shen (ed): Biomedical Nanomaterials. John Wiley & Sons Ltd (ISBN 978-3-527-33798-9), 2016

3) Y. Shen (Ed): Functional Polymers for Nanomedicine. London: Royal Society of Chemistry Publisher (ISBN 978-1-84973-620-6), 2013.

4) Q.H Sun, M Radosz, Y. Shen*, Chapter 3: Rational design of translational nanocarriers, in Functional Polymers for Nanomedicine. YQ Shen (ed). Royal Society of Chemistry, London, UK, p31-62.

5) B. Zhang, K. Wang, J. Si, M. Sui, Y. Shen, Charge-reversal polymers for biodelivery, in Bioinspired and Biomimetic Polymer Systems for Drug and Gene Delivery Edited by Gu, Zhongwei, (2015), 223-241.

6) J. Green, M Radosz*, and Y. Shen, Chapter 13. Near-critical micellization for nanomedicine: Enhanced drug loading, reduced burst release, in Functional polymers for nanomedicine. YQ Shen (ed). Royal Society of Chemistry, London, UK, p281-301.

7)J.B. Tang, DC Zhu, Y. Shen* (2012). Self-assembly of polymers into soft nanoparticles and nanocapsules in Supramolecular Chemistry: From Molecules to Nanomaterials (ISBN 978-0-470-74640-0), J.W. Steed and P.A. Gale (eds).  John Wiley & Sons Ltd, Chichester, UK, pp 3541-3562.

8)Y.Shen,* H. Tang, and  M. Radosz, E. A. Van Kirk, W. J. Murdoch, pH-responsive nanoparticles for drug delivery. Invited chapter in Drug Delivery Systems- Methods in Molecular Medicine, Kewal Jain (ed), Humana Press, 2008, 437:183-216.

Selected peer-reviewed journal articles

生物医用高分子合成

1) Q. Zhou, S.Q. Shao, J.Q. Wang, C. Xu, J.J. Xiang, Y. Piao, Z.X. Zhou, Q.S. Yu, J.B. Tang, X.R. Liu, Z.H. Gan, Z.     Gu,* and Y.Q. Shen*, Enzyme-Activatable Polymer-Drug Conjugate Augments Tumour Penetration and Treatment Efficacy, Nature Nanotechnology, 2019, 14, 799-809. https://doi.org/10.1038/s41565-019-0485-z.

2) X-C. Jiang, J.-J. Xiang, H. H. Wu, T. Y. Zhang, D. P. Zhang, Q. H. Xu, X.L. Huang, X.L. Kong, J.H. Sun, Y.L. Hu, K. Li, Y. Tabata, Y. Q. Shen*, J. Q. Gao*, Neural Stem Cells Transfected with Reactive Oxygen Species-Responsive Polyplexes for Effective Treatment of Ischemic Stroke, Advanced materials, 10.1002/adma.201807591

3) Q. Zhou, Y. Wang, J.J. Xiang, Y. Piao, Z.X. Zhou*, J.B. Tang, X.R. Liu, Y. Shen*, Stabilized calcium phosphate hybrid nanocomposite using a benzoxaborole-containing polymer for pH-responsive siRNA delivery, Biomaterials Science 2018, 6, 3178-3188

4) X. Sun, G. Wang, H. Zhang, S. Hu, X. Liu, J. Tang, Y. Shen*, The blood clearance kinetics and pathway of polymeric micelles in cancer drug delivery, ACS Nano 2018, 12, 6179-6192.

5) H. Yan, D. Zhu, Z. Zhou, X. Liu, Y. Piao, Z. Zhang, X. Liu, J. Tang, Y. Shen*, Facile synthesis of semi-library of low charge density cationic polyesters from poly(alkylene maleate)s for efficient local gene delivery, Biomaterials 2018, 178, 559-569.

6) N. Qiu, J. Gao, Q. Liu, J. Wang, Y. Shen*, Enzyme-responsive charge-reversal polymer-mediated effective gene therapy for intraperitoneal tumors, Biomacromolecules 2018, 19, 2308-2319.

7) D. Zhu, H. Yan, Z. Zhou, J. Tang, X. Liu, R. Hartmann, W.J. Parak, N. Feliu*, Y. Shen*, Detailed investigation on how the protein corona modulates the physicochemical properties and gene delivery of polyethylenimine (PEI) polyplexes, Biomaterials Science 2018, 6, 1800-1817.

H.P. Jiang, S.J. Wang, X.F. Zhou, L.Y. Wang, L.D. Ye, Z.X. Zhou, J.B. Tang, X.R. Liu, L.S. Teng, Y. Shen, New path to treating pancreatic cancer: TRAIL gene delivery targeting the fibroblast-enriched tumor microenvironment, Journal of Controlled Release 2018, 286, 254-263.

8) Y. Zhou, F. Huang, Y. Yang, P. Wang, Z. Zhang, Y. Tang, Y. Shen, K. Wang, Paraptosis-inducing nanomedicine overcomes cancer drug resistance for a potent cancer therapy, Small 2018, 14, online.

9) Z. Zhang, Y. Zhou, Z. Zhou*, Y. Piao, N. Kalva, X. Liu, J. Tang, Y. Shen*, Synthesis of enzyme-responsive phosphoramidate dendrimers for cancer drug delivery, Polymer Chemistry 2018, 9, 438-449.

10) H. Zhang*, Y. Zhu*, Y. Shen*, Microfluidics for cancer nanomedicine: From fabrication to evaluation, Small 2018, e1800360-e1800360.

11) H. Zhang, C. Fu, Y. Yi, X. Zhou, C. Zhou, G. Ying, Y. Shen*, Y. Zhu*, A magnetic-based SERS approach for highly sensitive and reproducible detection of cancer-related serum microRNAs, Analytical Methods, 2018, 10, 624-633.

12) W. Yu, M. Ye, J. Zhu, Y. Wang, C. Liang, J. Tang, H. Tao, Y. Shen, Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer for the photodynamic therapy of osteosarcoma, Nanomedicine: Nanotechnology, Biology, and Medicine, 14 (2018) 1099-1110.

13) F. Xu, H. Zhong, Y. Chang, D. Li, H. Jin, M. Zhang, H. Wang, C. Jiang, Y. Shen, Y. Huang, Targeting death receptors for drug-resistant cancer therapy: Codelivery of pTRAIL and monensin using dual-targeting and stimuli-responsive self-assembling nanocomposites, Biomaterials 2018, 158, 56-73.

14) J. Xiang, B. Wu, ZX. Zhou*, S. Hu, Y. Piao, Q. Zhou, G. Wang, J. Tang, X. Liu, Y. Shen*, Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy, Science China-Life Sciences 2018, 61, 436-447.

15) Z. Zhang, Y.C. Zhou, Z.X. Zhou*, Y. Piao, K. Kalva, X.R. Liu, J.B. Tang, Y. Shen*, Synthesis of enzyme-responsive phosphoramidate dendrimers for cancer drug delivery. Polymer Chemistry 2018, 9, 438-449.

16) S.Q. Shao. Q. Zhou, J.X. Si, J. Tang, X. Liu, M. Wang, J. Gao, K. Wang, R. Xu, and Y. Shen*, A noncytotoxic dendrimer of innate and potent anticancer and anti-metastatic activities, Nature Biomedical Engineering, 2017, 1, 745–757.

17) Z. Zhou, X. Liu, D. Zhu, Y. Wang, Z. Zhang, X. Zhou, N. Qiu, X. Chen, Y. Shen*, Nonviral cancer gene therapy: delivery cascade and vector nanoproperty integration, Advanced Drug Delivery Reviews, 2017, 115, 115-154.

18) M. Ye, Y. Han, J. Tang*, Y. Piao, X. Liu, Z. Zhou, J. Gao*, J. Rao, Y. Shen, A tumor-specific cascade amplification drug release nanoparticle for overcoming multidrug resistance in cancers,  Advanced Materials (2017), Ahead of Print, online.

19) Q. Sun, Z. Zhou, N. Qiu and Y. Shen*, Rational design of cancer nanomedicine: nanoproperty integration and synchronization, Advanced Materials 2017, 29, 1606628; DOI: 10.1002/adma.201606628

20) D. Zhu, H. Yan, X. Liu, J. Xiang, Z. Zhou, J. Tang, X. Liu and Y. Shen*, Intracellularly disintegratable polysulfoniums for efficient gene delivery, Advanced Functional Materials 2017, 27, 1606826. DOI: 10.1002/adfm.201606826

21) X. Liu, J. Xiang, D. Zhu, L. Jiang, Z. Zhou, J. Tang, X. Liu, Y. Huang and Y. Shen*, Fusogenic reactive oxygen species triggered charge-reversal vector for effective gene delivery, Advanced Materials  2016, 28, 1743-1752.

22) N. Qiu, X. Liu, Y. Zhong, Z. Zhou, Y. Piao, L. Miao, Q. Zhang, J. Tang, L. Huang and Y. Shen*, Esterase-activated charge-reversal polymer for fibroblast-exempt cancer gene therapy, Advanced Materials 2016, 28, 10613-10622..

23) J. Si, S. Shao, Y. Shen* and K. Wang*, Macrophages as active nanocarriers for targeted early and adjuvant cancer chemotherapy, Small  2016, 12, pp. 5108-5119.

24) Q. Sun, X. Ma, B. Zhang, Z. Zhou, E. Jin, Y. Shen*, E.A. Van Kirk, W.J. Murdoch, M. Radosz and W. Sun, Fabrication of dendrimer-releasing lipidic nanoassembly for cancer drug delivery, Biomaterials Science  2016, 4, 958-969.

25) X. Xi, S. Hu, Z. Zhou*, X. Liu, J. Tang and Y. Shen*, Dendrimers with the protocatechuic acid building block for anticancer drug delivery, Journal of Materials Chemistry B  2016, 4, 5236-5245.

26) C.-h. Xu, Q. Zhou, D.-c. Zhu, N.-s. Qiu, S.-q. Shao, X.-r. Liu and Y. Shen*, Esterase-activated self-immolative polymeric vector based on menschutkin reaction for gene delivery, Acta Polymerica Sinica 2017, 937-945.

27) Y.-c. Zhou, Z.-x. Zhou and Y. Shen*, Facile synthesis of poly(hydroxypropylene imine) dendrimer from a single monomer, Acta Polymerica Sinica 2017, 359-366.

28) Z. Zhou, W.J. Murdoch and Y. Shen*, Synthesis of an esterase-sensitive degradable polyester as facile drug carrier for cancer therapy, Journal of Polymer Science Part A-Polymer Chemistry 2016, 54, 507-515.

29) L.-M. Li, M. Han, X.-C. Jiang, X.-Z. Yin, F. Chen, T.-Y. Zhang, H. Ren, J.-W. Zhang, T.-J. Hou, Z. Chen, H.-W. Ou-Yang, Y. Tabata, Y. Shen and J.-Q. Gao*, Peptide-tethered hydrogel scaffold promotes recovery from spinal cord transection via synergism with mesenchymal stem cells, Acs Applied Materials & Interfaces  2017,  9, 3330-3342.

30) Y. Li, H. Wang, K. Wang, Q. Hu, Q. Yao, Y. Shen, G. Yu and G. Tang*, Targeted co-delivery of ptx and tr3 sirna by ptp peptide modified dendrimer for the treatment of pancreatic cancer, Small 2017, 13, 1602697.

31) X. Liu, Q. Huang, C. Yang, Q. Zhang, W. Chen, Y. Shen and M. Sui*, A multi-stimuli responsive nanoparticulate SN38 prodrug for cancer chemotherapy, Journal of Materials Chemistry B  2017, 5, 661-670.

32) B. Pelaz, C. Alexiou, R.A. Alvarez -Puebla, F. Alves, A.M. Andrews, S. Ashraf, L.P. Balogh, L. Ballerini, A. Bestetti, C. Brendel, S. Bosi, M. Carril, W.C.W. Chan, C. Chen, X. Chen, X. Chen, Z. Cheng, D. Cui, J. Du, C. Dullin, A. Escudero, N. Feliu, M. Gao, M. George, Y. Gogotsi, A. Grunweller, Z. Gu, N.J. Halas, N. Hampp, R.K. Hartmann, M.C. Hersam, P. Hunziker, J. Jian, X. Jiang, P. Jungebluth, P. Kadhiresan, K. Kataoka, A. Khademhosseini, J. Kopecek, N.A. Kotov, H.F. Krug, D.S. Lee, C.-M. Lehr, K.W. Leong, X.-J. Liang, M.L. Lim, L.M. Liz-Marzan, X. Ma, P. Macchiarini, H. Meng, H. Mohwald, P. Mulvaney, A.E. Nel, S. Nie, P. Nordlander, T. Okano, J. Oliveira, T.H. Park, R.M. Penner, M. Prato, V. Puntes, V.M. Rotello, A. Samarakoon, R.E. Schaak, Y. Shen, et. al, Diverse applications of nanomedicine, Acs Nano 2017, 11,  2313-2381.

33) J. Tan, H. Wang, F. Xu, Y. Chen, M. Zhang, H. Peng, X. Sun, Y. Shen and Y. Huang*, Poly-gamma-glutamic acid-based ggt-targeting and surface camouflage strategy for improving cervical cancer gene therapy, Journal of Materials Chemistry B  2017,  5, 1315-1327.

34) H. Wang, Y. Li, M. Zhang, D. Wu, Y. Shen, G. Tang and Y. Ping*, Redox-activatable atp-depleting micelles with dual modulation characteristics for multidrug-resistant cancer therapy, Advanced Healthcare Materials  2017, 6, 1601293. DOI: 10.1002/adhm.201601293

35) Y. Han, Y. Qian, X. Zhou, H. Hu, X. Liu, Z. Zhou, J. Tang* and Y. Shen, Facile synthesis of zwitterionic polyglycerol dendrimers with a beta-cyclodextrin core as MRI contrast agent carriers, Polymer Chemistry  2016, 7, 6354-6362.

36) H. Hu, Y. Sheng, M. Ye, Y. Qian, J. Tang* and Y. Shen, A porphyrin-based magnetic and fluorescent dual-modal nanoprobe for tumor imaging, Polymer 2016, 88, 94-101.

37) X. Liu, M. Wu, Q. Hu, H. Bai, S. Zhang, Y. Shen, G. Tang* and Y. Ping*, Redox-activated light-up nanomicelle for precise imaging-guided cancer therapy and real-time pharmacokinetic monitoring, Acs Nano 2016, 10, 11385-11396.

38) Y. Lu, L. Miao, Y. Wang, Z. Xu, Y. Zhao, Y. Shen, G. Xiang and L. Huang*, Curcumin micelles remodel tumor microenvironment and enhance vaccine activity in an advanced melanoma model, Molecular Therapy 2016, 24, 364-374.

39) X. Mao, J. Si, Q. Huang, X. Sun, Q. Zhang, Y. Shen, J. Tang, X. Liu and M. Sui*, Self-assembling doxorubicin prodrug forming nanoparticles and effectively reversing drug resistance in vitro and in vivo, Advanced Healthcare Materials 2016, 5, 2517-2527.

40) M. Ye, X. Wang, J. Tang*, Z. Guo, Y. Shen, H. Tian and W.-H. Zhu*, Dual-channel nir activatable theranostic prodrug for in vivo spatiotemporal tracking thiol-triggered chemotherapy, Chemical Science  2016, 7, 4958-4965.

41) B.-w. Zhao, Z. Zhou and Y. Shen*, Effects of chirality on gene delivery efficiency of polylysine, Chinese Journal of Polymer Science 2016, 34, pp. 94-103.

X. Zhou, X. Liu, B. Zhao, X. Liu*, D. Zhu, N. Qiu, Q. Zhou, Y. Piao, Z. Zhou, J. Tang and Y. Shen, Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDKI inhibitor RO-3306, Journal of Controlled Release 2016, 234, 90-97.

42) Z. Chen, L. Zhang*, Y. He, Y. Shen and Y. Li, Enhanced shRNA delivery and ABCG2 silencing by charge-reversible layered nanocarriers, Small 2015, 11, 952-962.

43) S. Hu, E. Lee, C. Wang, J. Wang, Z. Zhou, Y. Li, X. Li, J. Tang, D.H. Lee, X. Liu and Y. Shen*, Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy, Journal of Controlled Release 2015, 220, 175-179.

44) Y. Shen*, Elastin-like polypeptide fusion for precision design of protein-polymer conjugates with improved pharmacology, Science China-Materials 2015, 58, 767-768.

45)J. Wang, W. Mao, L.L. Lock, J. Tang*, M. Sui, W. Sun, H. Cui, D. Xu and Y. Shen, The role of micelle size in tumor accumulation, penetration, and treatment, Acs Nano 2015, 9, 7195-7206.

46) T.-Y. Zhang, B. Huang, H.-B. Wu, J.-H. Wu, L.-M. Li, Y.-X. Li, Y.-L. Hu, M. Han, Y. Shen, Y. Tabata and J.-Q. Gao*, Synergistic effects of co-administration of suicide gene expressing mesenchymal stem cells and prodrug-encapsulated liposome on aggressive lung melanoma metastases in mice, Journal of Controlled Release 2015, 209, 260-271.

47) Z. Zhou, W.J. Murdoch and Y. Shen*, A linear polyethylenimine (LPEI) drug conjugate with reversible charge to overcome multidrug resistance in cancer cells, Polymer 2015, 76, 150-158.

48) Z. Zhou, J. Tang, Q. Sun, W.J. Murdoch and Y. Shen*, A multifunctional PEG-PLL drug conjugate forming redox-responsive nanoparticles for intracellular drug delivery, Journal of Materials Chemistry B  2015, 3, 7594-7603.

49) M. Cao, X. Liu, T. Tang, M. Sui and Y. Shen*, Facile synthesis of size-tunable stable nanoparticles via click reaction for cancer drug delivery, Science China-Chemistry 2014, 57, 633-644.

50) Y. He, Y. Nie, G. Cheng, L. Xie, Y. Shen and Z. Gu*, Viral mimicking ternary polyplexes: a reduction-controlled hierarchical unpacking vector for gene delivery, Advanced Materials 2014, 26, 1534-1540.

51) K. Luo, B. He, Y. Wu, Y. Shen and Z. Gu*, Functional and biodegradable dendritic macromolecules with controlled architectures as nontoxic and efficient nanoscale gene vectors, Biotechnology Advances 2014, 32, 818-830.

52) U. Maddalena, A. Trachsel, P. Fankhauser, D.L. Berthier, D. Benczedi, W. Wang, X. Xi, Y. Shen and A. Herrmann*, Thioether profragrances: parameters influencing the performance of precursor-based fragrance delivery in functional perfumery, Chemistry & Biodiversity  2014, 11, 1700-1733.

53) L.-H. Peng, J. Niu, C.-Z. Zhang, W. Yu, J.-H. Wu, Y.-H. Shan, X.-R. Wang, Y. Shen, Z.-W. Mao, W.-Q. Liang and J.-Q. Gao*, TAT conjugated cationic noble metal nanoparticles for gene delivery to epidermal stem cells, Biomaterials 2014, 35, pp. 5605-5618.

54) G.-X. Ruan, Y.-Z. Chen, X.-L. Yao, A. Du, G.-P. Tang, Y.-Q. Shen, Y. Tabata and J.-Q. Gao*, Macrophage mannose receptor-specific gene delivery vehicle for macrophage engineering, Acta Biomaterialia 2014, 10, pp. 1847-1855.

55) G.-X. Ruan, T.-Y. Zhang, L.-M. Li, X.-G. Zhang, Y.-Q. Shen, Y. Tabata and J.-Q. Gao*, Hepatic-targeted gene delivery using cationic mannan vehicle, Molecular Pharmaceutics 2014, 11, 3322-3329.

56) S. Shao, J. Si, J. Tang, M. Sui and Y. Shen*, Jellyfish-shaped amphiphilic dendrimers: synthesis and formation of extremely uniform aggregates, Macromolecules 2014, 47, 916-921.

57) Q. Sun, X. Sun, X. Ma, Z. Zhou, E. Jin, B. Zhang, Y. Shen*, E.A. Van Kirk, W.J. Murdoch, J.R. Lott, T.P. Lodge, M. Radosz and Y.L. Zhao*, Integration of nanoassembly functions for an effective delivery cascade for cancer drugs, Advanced Materials 2014, 26, 7615-7621.

58) X.-J. Tang, M. Han, B. Yang, Y. Shen, Z.-G. He, D.-H. Xu and J.-Q. Gao*, Nanocarrier improves the bioavailability, stability and antitumor activity of camptothecin, International Journal of Pharmaceutics 2014, 477, 536-545.

59) X. Wu, X. Sun, Z. Guo, J. Tang*, Y. Shen, T.D. James, H. Tian and W. Zhu*, In Vivo and in situ tracking cancer chemotherapy by highly photostable nir fluorescent theranostic prodrug, Journal of the American Chemical Society 2014, 136, 3579-3588.

60) Z.X. Zhou, X.P. Ma, C.J. Murphy, E.L Jin, Q.H. Sun, Y. Shen*, E.A. Van Kirk, W.J. Murdoch: Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy. Angewandte Chemie-International Edition 2014, 53(41), 10949-10955.

61) J.Q. Wang, X.R. Sun, W.W. Mao, J.B. Tang, M.H. Sui, Y. Shen*, ZW Gu*: Prodrug nanocapsules responsive to tumor redox heterogeneity for cancer chemotherapy. Advanced Materials, 2013, 25(27), 3670-3676

62) E.L. Jin, B. Zhang, X.R. Sun, Z.X. Zhou, X.P. Ma, Q.H. Sun, J.B. Tang, Y. Shen*, EA Van Kirk, WJ Murdoch, M Radosz, Acid active cell-penetrating peptides for in vivo tumor-targeted drug delivery. Journal of the American Chemical Society  2013 Jan 16;135(2):933-40.

63) Z.X. Zhou, X.P. Ma, E.L. Jin, .JB. Tang, M.H. Sui, Y. Shen*, EA Van Kirk, WJ Murdoch, M Radosz. Linear-dendritic drug conjugates forming long-circulating nanorods for cancer-drug delivery. Biomaterials 2013, 34(22):5722-35.

64) M.Z. Ye, Y. Qian, J.B. Tang, H.J. Hu, M.H. Sui, Y. Shen. Targeted biodegradable dendritic MRI contrast agent for enhanced tumor imaging. Journal Controlled Release 2013, 169(3):239-45.

65) H.F. Zhang, J.Q. Wang, W.W. Mao, J. Huang, X.G. Wu, Y. Shen, M.H. Sui*, Novel SN38 conjugate-forming nanoparticles as anticancer prodrug: In vitro and in vivo studies, Journal of Controlled Release 2013 Mar 10;166(2):147-58.

66) B. Zhang, X.P. Ma, W.J. Murdoch, M. Radosz, Y. Shen*: Bioreducible poly(amido amine)s with different branching degrees as gene delivery vectors. Biotechnology and Bioengineering 2013, 110(3):990-8.

67) J.B. Tang, Y.Q. Sheng, H.J. Hu, Y. Shen*: Macromolecular MRI contrast agents: structures, properties and applications. Progress in Polymer Science  2013, 38(3–4), 462–502.

68) X.P. Ma, J.B. Tang, Z.X. Zhou, E.L. Jin, Q.H. Sun, B. Zhang, Y. Shen *, Facile synthesis of polyester dendrimers as drug delivery carriers. Macromolecules 2013, 46 (1),  37–42.

69) P.F. Gou,  W.W. Liu, W.W. Mao,  J.B. Tang,  Y. Shen and MH Sui* Self-assembling doxorubicin prodrug forming nanoparticles for cancer chemotherapy: synthesis and anticancer study in vitro and in vivo, Journal of Materials Chemistry B, 2013, 1, 284-292.

70) X.P. Ma, Q.H. Sun, Z.X. Zhou, E.L. Jin, J.B. Tang, E.V. Kirk, W.J. Murdoch and Y. Shen*, Synthesis of degradable bifunctional dendritic polymers as versatile drug carriers, Polymer Chemistry 2013, 4:812-819.

71) Q.H. Sun, M. Radosz, Y. Shen *, Challenges in design of translational nanocarriers, Journal of Controlled Release  2012, 164(2) 156-169.

72) M.H. Sui, H.F. Zhang, X. Di, J. Chang, Y. Shen, W.M. Fan*, G2 checkpoint abrogator abates the antagonistic interaction between antimicrotubule drugs and radiation therapy Radiotherapy and Oncology  2012, 104(2), 243-248.

73) M.Z. Ye, Y. Qian, Y. Shen, H.J. Hu, M.H. Sui, JB Tang*, Facile synthesis and in vivo evaluation of biodegradable dendritic MRI contrast agents. Journal of Materials Chemistry 2012, 22(29):14369-14377.

74) J. Yang, X.R. Sun, W.W. Mao, M.H. Sui, J.B. Tang*, Y. Shen*: Conjugate of Pt(IV)-histone deacetylase inhibitor as a prodrug for cancer chemotherapy. Molecular Pharmaceutics  2012, 9(10):2793-2800.

75) Z. Tyrrell, Y. Shen*, M. Radosz*: Multilayered nanoparticles for controlled release of paclitaxel formed by near-critical micellization of triblock copolymers. Macromolecules 2012, 45(11):4809-4817.

76) K.D. Lu, M.Z. Cao, W.W. Mao, X.R. Sun, J.B. Tang, Y. Shen*, M. Sui*: Targeted acid-labile conjugates of norcantharidin for cancer chemotherapy. Journal of Materials Chemistry   2012, 22(31):15804-15811.

77) Z.X. Zhou, Y. Shen*, J.B. Tang, E.L. Jin, X.P. Ma, Q.H. Sun, B. Zhang, E.A. Van Kirk, W.J. Murdoch, Linear polyethyleneimine-based charge-reversal nanoparticles for nuclear-targeted drug delivery. Journal of Materials Chemistry 2011, 21(47):19114-19123.

78) J. Yang, W.W. Liu, M.H. Sui*, J.B. Tang, Y. Shen*, Platinum (IV)-coordinate polymers as intracellular reduction-responsive backbone-type conjugates for cancer drug delivery. Biomaterials 2011, 32(34):9136-9143.

79)Z. Tyrrell, Y. Shen*, M. Radosz*, Near-critical fluid micellization for high and efficient drug loading: Encapsulation of paclitaxel into PEG-b-PCL micelles. Journal of Physical Chemistry C 2011, 115(24):11951-11956.

80)M.H. Sui, W.W. Liu, Y. Shen*, Nuclear drug delivery for cancer chemotherapy. Journal of Controlled Release  2011, 155(2): 227-236.

81)Y. Shen*, X.P. Ma, B. Zhang, Z.X.Zhou, Q.H. Sun, E.L. Jin, M.H. Sui, J.B. Tang, J.Q. Wang, M.H. Fan, Degradable dual pH- and temperature-responsive photoluminescent dendrimers. Chemistry-A European Journal 2011, 17(19): 5319-5326.

82)Z.C. Chen, J.B. Tang, Y. Shen*, X.P. Wang*, Click synthesis of topological macromolecules, Science China 2011, 41(2): 281-303.

83)H.D. Tang, C. Murphy, B. Zhang, Y. Shen*, EA Van Kirk, W J Murdoch, Curcumin polymers for cancer drug delivery, Biomaterials   2010, 31(27): 7139-7149.

84)Y. Shen*, Z.X. Zhou, P.S. Xu, E.A. Van kirk, W. J. Murdoch, Charge-reversal PAMAM dendrimer for nuclear drug delivery, Nanomedicine (UK)  2010, 5(8): 1205-1217.

85)H.D. Tang, C. Murphy, B. Zhang, Y. Shen*, E.A. Van Kirk, W.J. Murdoch, Amphiphilic curcumin conjugate forming nanoparticles: In vitro and In vivo anticancer activity, Nanomedicine (UK) 2010, 5(6): 855-865

86)Z. Tyrrell, Y. Shen, M. Radosz*, Fabrication of micellar nanoparticles for drug delivery through the Self-assembly of block copolymers. Progress in Polymer Science 2010, 35(9): 1128-1143.

87)H. Ma, K. Jones, R. Guo, P.S. Xu, Y. Shen and J Ren*, Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: Role of endoplasmic reticulum stress, Clinical and Experimental Pharmacology and Physiology 2010, 37: 460–465.

88)Y. Shen*, EL Jin, B Zhang, C Murphy, MH Sui, HD Tang, MH Fan, EA Van Kirk, WJ Murdoch, Prodrug lipid forming high drug loading multifunctional nanocapsules for cancer intracellular drug delivery, Journal of the American Chemical Society 2010, 132:4259-4265.

89)X. Ma, J. Tang, Y. Shen*, M. Fan, H. Tang and M. Radosz, Facile synthesis of dendrimers from sequential click coupling of asymmetrical monomers, Journal of American Chemical Society, 2009, 131:14795–14803.

90)Z. Zhou, Y. Shen *, J. Tang, M. Fan, E. A Van Kirk , W. J Murdoch, M. Radosz, Targeted charge-reversal polymer drug conjugate for nuclear drug delivery, Advanced Functional Materials, 2009, 19:3580 - 3589.

91)Y. Shen,* Y. Zhan, H. Tang, P. A. Johnson, E. A. Van Kirk, W. Murdoch, Degradable poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery, Nanomedicine: Nanotechnology, Biology and Medicine, 2009, 5:192-201.

92)S. Turdi,; P. Xu, Q. Li, Y. Shen*, P. Kerram, J. Ren*, Amidization of doxorubicin alleviates doxorubicin-induced contractile dysfunction and decreased survival in murine cardiomyocytes, Toxicology Letters 2008, 178:197-201.

93)Y. Shen,* Y. Zhan, J. Tang, P. A. Johnson, M. Radosz, E. A. Van Kirk, W. Murdoch, Multifunctioning pH-responsive nanoparticles from hierarchical self-assembly of polymer brush for cancer chemotherapy, AIChE Journal 2008, 54:2979-2989.

94)P. Xu, S. Li, J. Ren*, W. J. Murdoch, M. Radosz, Y. Shen*, Virion-mimicking nanoparticles for gene delivery,  Angewandte Chemie International Edition 2008, 47:1260-1264.

95)W.J. Murdoch, E.A. Van Kirk, D.D. Isaak, Y. Shen: Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts. Gynecologic Oncology 2008, 110:251-255.

96)P. Xu, E. A. Van Kirk, Y. Zhan, W. J. Murdoch, M. Radosz, Y. Shen,* Targeted charge-reversal nanoparticles for nuclear drug delivery, Angewandte Chemie International Edition, 2007, 46:4999-5002. Highlighted http://www.nanowerk.com/spotlight/spotid=2113.php

97)N. Wang, A. Dong, M. Radosz, Y Shen,* Degradable thermoresponsive polyethylene glycol analog, Journal of Biomedical Materials Research A, 2007, 84A:148 - 157.

98)N. Wang, A. Dong, E. A. Van Kirk, H. Tang, W. Murdoch, M. Radosz, Y Shen,* Degradable polyethylene glycol analog as versatile drug delivery carriers, Macromolecular Bioscience, 2007, 7: 1187-1198.

99)W. Jin, Y. Zhan, E. A. Van Kirk, L. Liu, P. Xu, W. Murdoch, M. Radosz, Y. Shen,* Degradable cisplatin-releasing core-shell nanogels from zwitterionic poly(beta-aminoester)-graft-PEG for cancer chemotherapy, Drug Delivery 2007,  14:279-286.

100)P. Xu, S. Li, J. Ren, W. J. Murdoch, M. Radosz, Y. Shen*, Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes, Biotechnology and Bioengineering, 2006, 95:893-903.

101)P. Xu, E. A. Van Kirk, W. J. Murdoch, Y. Zhan, D. D. Isaak, M. Radosz, Y. Shen*, Anticancer efficacies of cisplatin-releasing nanoparticles, Biomacromolecules, 2006, 7:829-835.

102)Selected as one of the four the Most Intriguing work by CAS scientists for 2Q of 2006 from over 200,000 documents per quarter, including articles from nearly 9,500 journals, and patents from 50 active patent-issuing authorities from around the world.

103)P. Xu, E. A. Van Kirk, S. Li, J. Ren, W. J. Murdoch, M. Radosz, Y. Shen*, Highly stable core-surface crosslinked nanoparticles as cisplatin carriers, Colloids and Surfaces B: Biointerfaces, 2006, 48:50-57. 

104)H.Tang, M. Radosz, Y. Shen,* Synthesis and self-assembly of thymine- and adenine-containing homopolymers and diblock copolymers, Journal of Polymer Science Part A: Polymer Chemistry, 2006, 44:5995-6006.

105)H.Tang, M. Radosz, Y. Shen,* Template-atom transfer radical polymerization of diaminopyrimidine derivatized monomer in the presence of uracil-containing polymer, Journal of Polymer Science Part A: Polymer Chemistry, 2006, 44:6607-6615.

106)P. Xu, H. Tang, S. Li, J. Ren, E. A. Van Kirk, W. J. Murdoch, M. Radosz, Y. Shen,* Enhanced stability of core-surface crosslinked micelles fabricated from amphiphilic brush copolymers, Biomacromolecules, 2004, 5:1736-1744.

授权专利

1.申有青等，PCT世界专利：含硫脲树枝状大分子和含硫脲超支化聚合物及其制备方法和应用，PCT/CN2015/07/1874 (正在进入美国专利)

2.申有青、唐建斌等，中国发明专利：一种聚酯树枝状大分子的制备方法，专利号：ZL200910100118.0，授权日： 2011.5.25

3.申有青、唐建斌等，中国发明专利：喜树碱及其衍生物的自乳化药物前体及其应用，专利号：ZL200910102143.2，授权日： 2011.8.20 （成果已转让）

4.申有青、胡诗琪等：利用双亲性药物包载疏水性抗肿瘤药物的方法及制剂，专利号: ZL 2013 1 0553279.1 （成果已转让）

5.Maciej Radosz, Youqing Shen, Huadong Tang,美国发明专利，Highly active catalyst for atom transfer radical polymerization，专利号：US7994087B2，授权日：2011.8.9

6.S. Zhu, Y. Shen, R. Pelton, Tertiary amine methacrylate-based macromonomers and polymers, US Patent number: 6630557, Issue date: 7 Oct 2003.

申请专利

1.申有青、唐建斌、隋梅花、王金强，自纳米化7－乙基－10－羟基喜树碱（SN38）的纳米抗癌药物的制备方法，中国专利申请：申请号：201010561727.9，申请日：2010.11.26；公开(公告)号： CN102060991A.

2.申有青;唐建斌;苟鹏飞;隋梅花，一种自乳化阿霉素纳米药物及其制备方，中国专利申请：申请号：201110113954.X，申 请 日：2011.05.04 ，公开(公告)号：CN102188717A， 公开(公告)日：2011.09.21.       

3.Y. Shen, H. Tang, E. Van Kirk, W. J. Murdoch, M. Radosz,  Curcumin-containing polymers as prodrugs or prodrug carriers.  US Patent Application 20120003177, Kind Code A1, January 5, 2012; PCT NO:  PCT/US09/57303.

4.Y. Shen, P. Xu, Charge reversible polymers. US Patent Application Number: 13/033,247; Publication number: US 2011/0244046 A1; Filing date: 23 Feb 2011.

5.Y. Shen, H. Tang, M. Radosz, Amine-containing compounds for enhancing the activity of ATRP catalysts and removal of the terminal halogen groups from the ATRP polymer products. Application number: 11/958,336; Publication number: US 2009/0156771 A1; Filing date: 17 Dec 2007

6.M. Radosz, Y. Shen, E. A. Van Kirk, W. J. Murdoch, Degradable polymeric nanogel for drug delivery. US patent Application number: 11/599,531; Publication number: US 2007/0224164 A1; Filing date: 14 Nov 2006

7.M. Radosz, Y. Shen, Processing nanoparticles by micellization of blocky-copolymers in subcritical and supercritical solvents, US Patent Application 20100270695, Kind Code  A1, Appl. Date:  October 28, 2010; PCT NO:  PCT/US07/19370.

8.M. Radosz and Y. Shen, Poly(ionic liquid)s as new materials for CO2 separation and other applications, US Patent Application 20090266230, Kind Code  A1, Appl. Date:  October 29, 2009; PCT NO:  PCT/US05/27833

9.M. Radosz, Y. Shen, H. Tang, Polymers and copolymers of ionic liquids as radio frequency absorbing materials, US Patent Application 20080125559, Kind Code  A1, Appl Date:  May 29, 2008; PCT NO:  PCT/US05/40651.

招生信息

本课题组的研究集中在以新功能材料的设计与合成为基础的生物纳米材料/工程的研究。主要研究工作内容为新功能生物纳米材料的设计与合成、智能纳米材料与药物及生物大分子的组装及智能纳米载体材料在生物、医学上的应用， 特别是智能纳米药物载体用于癌症的治疗和早期诊断。该研究是化学、材料、高分子、化学工程、生物工程、分子/细胞生物学、药学、肿瘤医学、临床医学等学科的交叉。不同专业背景的同学在应用自己的专业知识的同时，将与其它专业背景的同学及临床医师合作进行科研工作并完成课题。因此，上述专业的同学都可以找到自己感兴趣的课题，并得到多学科背景的综合训练，大大拓宽知识面。

欢迎各专业有识之士加入本课题组，更多信息可移步课题组网站（http://che.zju.edu.cn/others/bionano）