COLLEGE OF ENGINEERING AND APPLIED SCIENCE
- B.S., Department of Chemistry, Zhejiang University, 1991
- D. Sc., Department of Polymer Science and Engineering, Zhejiang University, 1995
- Ph.D., Department of Chemical Engineering, McMaster University, 2001
- 01/11-02/10 Research Scientist, Casco Impregnated Papers, Akzol Nobel Inc., Ontario, Canada
- 02/11-07/6, Assistant Professor, Department of Chemical & Petroleum Engineering, University of Wyoming, Laramie, WY82071
- 07/6-08/6, Tenured Associate Professor and Director of Soft Materials Laboratory, Department of Chemical and Petroleum Engineering/Department of Chemistry/Program of Molecular Cellular and Life Sciences (MCLS)/Center for Cardiovascular Research and Alternative Medicines, University of Wyoming
- 08/7-, Qiushi Chair Professor and NSFC Distinguished Young Scholar, Director of Center for Bionanoengineering (CBNE), Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou, China 310027 Adjunct Professor, Soft Materials Laboratory (SML) and Department of Chemical and Petroleum Engineering, University of Wyoming
- Polymer Reaction Engineering
- Drug Delivery
- Gene Delivery
- Cancer Chemotherapy
- 1999, 5 Chinese Ministry of Education, Outstanding Dissertation Award
- 2006,5 Sam D. Hakes Outstanding Graduate Research and Teaching Award, University of Wyoming
- 2006, Paper Anticancer efficacies of cisplatin-releasing nanoparticles, Biomacromolecules, 2006, 7, 829-835. 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.
- 2007,4 Outstanding Dissertation Award to PhD Graduate Shijie Ding, Advisor, University of Wyoming
- 2007,4 Outstanding Dissertation Award to PhD Graduate Peisheng Xu, Advisor, University of Wyoming
- 2007, 6 Early tenure and promotion, University of Wyoming
- 2008,8 National Science Fund for Distinguished Young Scholars (50888001), China
Supported by NSF, DoD, NIH, Am Cancer Soc, and NSFC, my research is focused on rational design and synthesis of novel polymers that may have applications in biomaterials, biotechnology and pharmaceuticals as well as other applications. Currently, two research directions are ongoing.
1. Biodelivery: Polymer Nanocarriers for Targeted Drug Delivery and Gene Delivery to Cancer
Cancer has dethroned heart disease as the top killer among Americans under the age of 85. Most patients, although initially responsive, eventually develop and succumb to drug-resistant metastases. For example, the success of typical postsurgical regimens for ovarian cancer is limited by primary tumors being intrinsically or becoming refractory to treatment. First-line treatment yields about 30% complete pathologic remission and an overall response rate of 75%, but the disease usually recurs within 2 years of the initial treatment. Thus, drug resistance is a major obstacle to the successful cancer chemotherapy, particularly at advanced stages.
Cancer cells have many intrinsic and acquired drug resistance mechanisms to mitigate the cytotoxic effects of anti-cancer drugs (Figure 1). These mechanisms include the loss of surface receptors or transporters to slow drug influx, cell-membrane-associated multidrug resistance to remove drugs, specific drug metabolism or detoxification, intracellular drug sequestration, overexpression of Src tyrosine kinase and splicing factor SPF45, increased DNA-repair activity, altered expression of oncogenes and regulatory proteins and increased expression of antiapoptotic genes and mutations to resist apoptosis, and etc.
Our research in this area is focused on using active nanocarriers to deliver drugs to the specific subcellular targets to overcome cancer drug resistance for high therapeutic efficacy. Generally, we start from design and synthesis of new stimulus-responsive multifunctional polymers and fabrication of programmed or active nanocarriers. These nanocarriers are then tested in vitro and in vivo.
The fist system is cancer-targeted lysosomal triggered fast release nanoparticles (Figure 2). In vitro and in vivo evaluation shows that drugs in these nanoparticles have higher anticancer activity than free and conventional nanoparticle-encapsulated drugs. This work is highly recognized as one of the four “most intriguing” work of 2006-2Q selected by CAS from over 200,000 documents per quarter.The second system is nuclear localization nanoparticles for nuclear drug delivery (Figure 3). The central hypothesis is that delivery of drugs to the immediate vicinity of the anticancer drug targets ? the nuclear DNA? can circumvent both of the cell-membrane associated multidrug resistance and the intracellular drug resistance mechanisms. The big challenge is how to activate the nuclear localization agents only inside cancer cells. We developed a charge-reversal technique and successfully solved the problem (Angewandte Chemie International Edition, 2007, 46, 4999-5002). Highlightedhttp://www.nanowerk.com/spotlight/spotid=2113.phpGene Delivery
In polymer-mediated gene delivery, cationic polymers generally complex plasmids to compact them into nanoparticles and to shield their negative charges for effective cellular internalization. Tight packing is also needed for DNA trafficking to the nucleus and protection from degradation by enzymes. However, this tight complexation has been found as one of the major barriers to efficient DNA transcription because in the nucleus the complexed DNA is inaccessible for the transcription machine. Facilitated dissociation of the complexes using short, reversibly crosslinked, degradable, or low positively-charged cationic polymers or charge-reversible amphiphiles has been shown to significantly enhance transgenic efficiency.
Our research in this area is rational design of polymers that can deliver loosely packed or even free DNA (Scheme 1 and Figure 4) into the nucleus for high transfection efficiency. Our ultimate goal is to develop polymer gene therapy for cancer or other diseases.
Synthesis and applications of biodegradable dendrimers
Polyester dendrimers are attractive for in vivo delivery of bioactive molecules due to their biodegradability, but their synthesis generally requires multistep reactions with intensive purifications. A highly efficient approach to the synthesis of dendrimers by simply “sticking” generation by generation together is achieved by combining kinetic or mechanistic chemoselectivity with click reactions between the monomers. In each generation, the targeted molecules are the major reaction product as detected by MALDI-TOF MS. The only separation needed is to remove the little unreacted monomer by simple precipitation or washing. This simple click-like process without complicated purification is particularly suitable for the synthesis of custom-made polyester dendrimers. Currently, we are further improving this method for accelerated synthesis and using the dendrimers in in vivo gene and drug delivery as well as the magnetic resonance imaging (Journal of American Chemical Society 2009, 131 (41), 14795–14803).
- Z. Zhou, Y. Shen,* E. A. Van Kirk, W. J. Murdoch, pH-triggered charge-reversal polylysine for nuclear drug delivery,Advanced Functional Materials 2009,online view.
- X. Ma, Y. Shen*, J. Tang, M. Fan, H. Tang, M. Radosz, synthesis of degradable dendrimers by asymmetric monomers,Journal of American Chemical Society 2009, 131 (41), 14795–14803.
- 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, 42, 4531-4538.
- 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.
- 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.
- 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.
- Y. Shen*, H. Tang, M. Radosz, 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.
- 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.
- 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. Highlightedhttp://www.nanowerk.com/spotlight/spotid=2113.php Top References for Molecular Imaging–June 2007,http://interactive.snm.org/docs/June_MI_TopReferences.pdf
- N. Wang, A. Dong, M. Radosz, Y Shen*, Degradable thermoresponsive polyethylene glycol analog, Journal of Biomedical Materials Research A 2007, 84A:148 - 157.
- N. Wang, A. Dong, E. A. Van Kirk, H. Tang, W. Murdoch, M. Radosz, Y Shen*, Synthesis of degradable functional poly(ethylene glycol) analogs as versatile drug delivery carriers, Macromolecular Bioscience 2007, 7: 1187-1198.
- 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.
- 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. 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.
2. Controlled/Living radical polymerization and CO2 separation
The second ongoing research area focuses on developing highly active catalysts for atom transfer radial polymerization (ATRP). ATRP generally requires a catalyst/initiator molar ratio of 0.1 to 1 and catalyst/monomer molar ratio of 0.001 to 0.01 (i.e., catalyst concentration: 1,000–10,000 ppm vs. monomer).We found a new copper-based complex CuBr/N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) as a versatile and highly active catalyst for acrylic, methacrylic and styrenic monomers. The catalyst mediated ATRP at a catalyst/initiator molar ratio of 0.005 and produced polymers with well-controlled molecular weights and low polydispersities. ATRP occurred even at a catalyst/initiator molar ratio as low as 0.001 with copper concentration in the produced polymers as low as 6–8 ppm (catalyst/monomer molar ratio = 10-5). We also found that amines could be used as versatile reducing agents for enhancing ATRP catalyst activities.
We also found a new class of polymers, poly(ionic liquid)s, potentially used as sorption and membrane materials for CO2separation.
- Y. Shen,* H. Tang, M. Radosz, Controlled/“living” radical polymerization of vinyl acetate, in Controlled/Living Radical Polymerization: Progress in ATRP, ACS Symposium Series, (K. Matyjaszewski (ed), Volume 1023, page 139-158(2009).
- L. Zhang, H. Tang, J. Tang, Y. Shen,* L. Meng, M. Radosz, N. Arulsamy, Pentadentate copper halide complexes have higher catalytic activity in atom transfer radical polymerization of methyl acrylate than hexadentate complexes.Macromolecules 2009,42, 4531-4538
- H. Tang, M. Radosz, Y. Shen,* Atom transfer radical polymerization and copolymerization of vinyl acetate catalyzed by copper halide/terpyridine. AIChE Journal 2009, 55, 737-746.
- X. Hu, M. Radosz, Y. Shen, Flue-Gas Carbon Capture on Carbonaceous Sorbents: Toward a Low-Cost Multifunctional Carbon Filter for ‚Green’ Energy Producers, Industrial & Engineering Chemistry Research 2008, 47:3783-3794.“Most accessed article” and highlighted in http://news.sciencemag.org/sciencenow/2008/05/16-02.html
- J. Tang, M. Radosz, and Y. Shen,* Poly(ionic liquid)s as transparent microwave absorbing materials, Macromolecules, 2008, 41:493-496..
- H. Cong, J. Zhang, M. Radosz, Y. Shen,*Carbon nanotube composite membranes of brominated poly(2,6-diphenyl-1,4-phenylene oxide) for gas separation, Journal of Membrane Science 2007, 294:178-185.
- H. Cong, X Hu, M. Radosz, Y. Shen,* Brominated Poly(2,6-diphenyl-1,4-phenylene oxide) and Its SiO2 Nanocomposite Membranes for Gas Separation, Industrial & Engineering Chemistry Research 2007, 46:2567-2575.
- 21) H. Cong, M. Radosz, Y. Shen,* Polymer-inorganic nanocomposite membranes for gas separation, Separation and Purification Technology 2007, 55:281-291.
- H. Tang, N. Arulsamy, M. Radosz, Y. Shen*, N. V. Tsarevsky, W. A. Braunecker, W. Tang, K. Matyjaszewski*, Highly active catalyst for atom transfer radical polymerization, Journal of American Chemical Society, 2006, 128:16277-16285. Highlighted in Chemical & Engineering News, 84(44), October 30, 2006, 40-41.
- W. Winoto, H. Adidharma, Y. Shen, Y., M. Radosz*, Micellization Temperature and pressure for polystyrene-block-polyisoprene in subcritical and supercritical propane. Macromolecules, 2006, 39:8140-8144.
- S. Ding, M. Radosz, Y. Shen*, Magnetic supported catalyst for ATRP. Chapter in Progress in Controlled/Living Polymerization: From Synthesis to Materials, ACS Symposium. Series 2006, 944:71-84.
- S. Ding, M. Radosz, Y. Shen*, Magnetic nanoparticle supported catalyst for atom transfer radical polymerization,Macromolecules, 2006, 39:6399-6405. Most-Accessed Articles in Macromolecules: July-September, 2006
- H. Tang, M. Radosz, Y. Shen*, CuBr2/N,N,N’,N’-tetra[(2-pyridal)-methyl]ethylenediamine –tertiaryamine as highly active and versatile catalyst for atom transfer radical polymerization via activator generated by electron transfer,Macromolecular Rapid Communication, 2006, 27, 1127-1131.
- J. Tang, W. Sun, H. Tang, M. Radosz, Y. Shen*, Low pressure CO2 sorption in ammonium based poly(ionic liquid)s,Polymer, 2005, 46:12460-12467.
- J. Tang, W. Sun, H. Tang, M. Radosz, Y. Shen*, Poly(ionic liquid)s as new materials for CO2 absorption, Journal of Polymer Science Part A: Polymer Chemistry, 2005, 43:5477-5489.
- S. Ding, M. Radosz, Y. Shen*, Ionic liquid supported catalyst for atom transfer radical polymerization, Macromolecules 2005, 38:5921-5928.
- J. Tang, H. Tang, W. Sun, H. Plancher, M. Radosz, Y. Shen*, Poly(ionic liquid): A new material for enhanced and fast absorption of CO2, Chemical Communication, 2005, 3325-3327. (Highlighted in Chemical & Engineering News’s cover story Membranes For Gas Separation 2005, 83 (40) 49-57).
- J. Tang, H. Tang, W. Sun, M. Radosz, Y. Shen*, Enhanced CO2-absorption of poly(ionic liquid)s, Macromolecules 2005, 38:2037-2039.
- S. Ding, H. Tang, M. Radosz, Y. Shen*, Atom transfer radical polymerization of ionic liquid 2-(1-butylimidazolium-3-yl)ethyl methacrylate tetrafluoroborate, Journal of Polymer Science, Part A: Polymer Chemistry 2004, 42:5794-5801.
- Y. Shen,* H. D. Tang, and S. Ding, Catalyst separation in atom transfer radical polymerization, Progress in Polymer Science, 2004, 29, 1053-1078.
- 15) J. Yang, S. Ding, M. Radosz, Y. Shen*, Reversible catalyst supporting via hydrogen bonding-mediated self assembly for atom transfer radical polymerization of MMA, Macromolecules, 2004, 37:1728-1734.