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Dr. Youqing Shen

Youqing Shen, Ph.D., Associate Professor
Department of Chemical & Petroleum Engineering
Department of Chemistry
Director: Soft Materials Laboratory (SML)
University of Wyoming
Room 3022, Engineering Building
1000 E. University Avenue
Laramie, WY 82071
Phone/Voicemail: (307) 766-2501
Fax: (307) 766-6777 

Education
  • B.S., Zhejiang University, 1991
  • D. Sc., Zhejiang University, 1995
  • Ph.D., McMaster University, 2001
Work Experience
  • Akzol Nobel Inc., 2002

Specialization: Polymer Reaction Engineering; Living Polymerization Technologies; Biomaterials; Drug Delivery; Gene Delivery; Cancer Chemotherapy; Nanotechnologies.

Awards:

  • 2007 Early tenure and promotion
    2007 Outstanding Dissertation Award to PhD Graduate Sijie Ding, Advisor
    2006 Sam D. Hakes Outstanding Graduate Research and Teaching Award
    2000-2001 Ontario Graduate Scholarship in Science and Technology (OGSST), McMaster University
    1999-2000 Shell Canada Graduate Student Research Fellow, McMaster University
    1999 Outstanding Dissertation Award, Chinese Ministry of Education

Group Photo

Current Research
My research is focused on rational design and synthesis of novel polymers that may eventually have applications in biomaterials, biotechnology and pharmaceuticals as well as other applications. Currently, three research directions are ongoing.

Research Directions

  1. Biodelivery: Polymer Nanocarriers for Targeted Drug Delivery and Gene Delivery to Cancer
    Supports: BRIN Biomedical Network
    NIH-INBRE
    NSF-CBET 0401982
    American Cancer Society Research Scholar Grant RSG-06-118-01-CDD
    NSF-DMR 0705298
    DOD Breast Cancer Concept Award BC062422

    Drug Delivery
    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.

    Figure 1.Illustration of some drug resistance mechanisms of cancer cells

    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 first 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.(link to the PDF file)

    tumors on mice

    Figure 2. The numbers of tumors on intestine/ mesentery (per cm2) of the nude mice. Cisplatin dose was 10 mg/kg/treatment. Mice were treated twice at fourth and the fifth weeks after inoculation of SKOV-3 cells. Data represent mean value +/- S.E.

    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).
    Highlighted http://www.nanowerk.com/spotlight/spotid=2113.php

    Figure 3.Nuclear localization of the PEI-based charge-reversal nanoparticles observed by confocal scanning laser microscopy after cultured with SKOV-3 cells for 24 h at 37 ?C. The nuclei were stained with DRAQ5 (blue). The nanoparticles loaded with PKH26 were assigned to red. Pink spots were nanoparticles colocalized in the nuclei.

    Gene 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.


    Scheme 1. Virion-mimicking nanocapsule formation via a pH-controlled hierarchical self-assembly of the PCL/PDEA/PEG terpolymer brush and DNA. The PDEA chains were positively charged by protonation at pH 5 (a); They complexed with DNA and formed a hydrophilic core; the hydrophobic PCL chains collapsed on the core, forming a membrane surrounding the core; the hydrophilic PEG chains were incompatible with the hydrophobic PCL layer and thus were extended in the aqueous solution, forming the hydrophilic outer layer (b); After the solution pH was raised to pH 7.2, the PDEA chains were deprotonated, became neutral and insoluble, and thus dissociated from the DNA, leaving free DNA in the core (c).

    artifical virus

    Figure 4. The artificial virius: free DNA in polymer nanocapsules

    • Y. Shen,* H. Tang, and M. Radosz, "pH-responsive nanoparticles for drug delivery" Invited chapter in Drug Delivery Systems- Methods in Molecular Medicine, Kewal Jain (ed), Humana Press, to be published in 2007.
    • 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
    • P. Xu, S.-Y. Li, Q. Li, E. A. Van Kirk, J. Ren,* Z. Zhang, W. J. Murdoch, Y. Shen,* Virion-mimicking nanocapsules from pH-controlled-hierarchical self-assembly for gene delivery, Submitted.
    • Y. Zhan, E. A. Van Kirk, W. Murdoch, M. Radosz, Y Shen,* "Multifunctioning pH-responsive nanoparticles from hierarchical self-assembly of polymer brush for cancer chemotherapy', Submitted to Biomacromolecules.
    • N. Wang, A. Dong, M. Radosz, Y Shen,* "Degradable thermoresponsive polyethylene glycol analogs", Journal of Biomedical Materials Research A, in press.
    • N. Wang, A. Dong, E. A. Van Kirk, H. Tang, W. Murdoch, M. Radosz, Y Shen,* "Degradable polyethylene glycol analogs as versatile drug delivery carriers", Macromolecular Bioscience, in press.
    • 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, 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 (linked to the PDF file).
    • 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.
    • 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.


  2. Advanced Polymeric Materials and Catalysts for Atom Transfer Radical Polymerization Supports: NSF-CBET 0650608: Self-Assembling Polymers: Synthesis and Characterization

    NSF-CBET 0352812: Template-Controlled Living Polymerization for Synthesis of Self-Assembling Polymers

    Association of polymer chains with uncontrolled distribution of hydrogen bonding sites leads to random clusters and three-dimensional networks through a process of random intra- and intermolecular bonding which leads to self- and cross-association or both. By contrast, uniform polymer chains with a well-defined distribution of hydrogen-bonding sites can self assemble with their complementary chains, that is, they can form highly aligned chain duplexes with well-defined bond sequences. Such polymer self-assembly, reminiscent of DNA self-assembly, can lead to valuable biotic and abiotic advanced materials. The challenge is how to synthesize such self-assembling polymers. Our current research is using living polymerization techniques to synthesize such self-assembling polymers. The AFM image shows the V-shape of a self-assembling block copolymer synthesized via a two-step ATRP method (Figure 5). In addition, highly active and supported ATRP catalysts have also been developed.

    AFM image

    Figure 5: AFM image of block copolymer on mica surface of in DMSO/DMF solution


    • 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.
    • 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.
    • 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.
    • S. Ding, M. Radosz, Y. Shen*, "Magnetic nanoparticle supported catalyst for atom transfer radical polymerization", Macromolecules, 2006, 39, 6399-6405. One of the 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.
    • 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*, "Ionic liquid supported catalyst for atom transfer radical polymerization", Macromolecules 2005, 38, 5921-5928.
    • 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 (Ranked top 19 of the most download papers in the journal in 2005).
    • S. Ding, M. Radosz, Y. Shen*, "A new tetradentate ligand for atom transfer radical polymerization" Journal of Polymer Science Part A: Polymer Chemistry, 2004, 42, 3553-3562.
    • S. Ding, M. Radosz, Y. Shen*, "Atom transfer radical polymerization of N,N-dimethylacrylamide", Macromolecular Rapid Communication, 2004, 25, 632-636.
    • 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.
    • S. Ding, J. Yang, M. Radosz, Y. Shen*, "Atom transfer radical polymerization of methyl methacrylate by reversibly supported catalysts on silica gel via self assembly", Journal of Polymer Science Part A: Polymer Chemistry 2004, 1, 22-30.


  3. CO2 Separation
    The global warming due to the increased atmospheric CO2 concentration resulting from increasing consumption of fossil fuel is becoming an important environmental issue today. Carbon sequestration, which captures CO2 from large point sources such as fossilfuel-fired electrical power-generation plants and stores it in geological formations, has been proposed as a solution to this problem. Efficient separation of CO2 is key to the economically viable sequestration efforts. Ionic liquids, organic salts that are liquids at low temperatures (<100 °C), have been explored asnonvolatile and reversible CO2 absorbents for CO2 separation because of their high CO2 solubility. We found the polymers from ionic liquid monomers, named poly(ionic liquid)s, had higher CO2 sorption capacity with fast sorption/desorption rates(Figure 6). They are promising new materials for CO2 separation. We are currently are looking into polymer nanocomposite membranes for CO2 separation.
    CO2 absorbtion

    Figure 6. CO2 absorption of the polymers (a-e) and their corresponding monomers [VBTMA][BF4](f), [MATMA][BF4](g), [VBBI][BF4](h), ([MABI][BF4](i), and ionic liquid [bmim][BF4] (j) as a function of time (592.3 mmHg CO2, 22 º C).

    • 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
    • A. Blasig, J. Tang, X. Hu, Y. Shen, M. Radosz.* "Magnetic suspension balance study of carbon dioxide solubility in ammonium-based polymerized ionic liquids: Poly(p-vinylbenzyltrimethyl ammonium tetrafluoroborate) and poly([2-(methacryloyloxy)ethyl] trimethyl ammonium tetrafluoroborate)". Fluid Phase Equilibria 2007, 256, 75-80.
    • 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
    • X Hu, H. Cong, Y. Shen, M. Radosz,* "Nanocomposite Membranes for CO2 separations: Silica/Brominated PPO [Poly(phenylene oxide]", Industrial & Engineering Chemistry Research 2007, 46, 1547-1551
    • H. Cong, M. Radosz, Y. Shen,* "Polymer-inorganic nanocomposite membranes for gas separation", Separation and Purification Technology 2007, 55, 281-291.
    • X. Hu, J. Tang, A. Blasig, Y. Shen, M. Radosz*, "CO2 permeability, diffusivity and solubility in polyethylene glycol-grafted polyionic membranes and their CO2 selectivity relative to methane and nitrogen". Journal of Membrane Science 2006, 281, 130-138.
    • 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.
    • 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 (also 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.
    • Tang, Huadong; Tang, Jianbin; Ding, Shijie; Radosz, Maciej; Shen, Youqing. Atom transfer radical polymerization of styrenic ionic liquid monomers and carbon dioxide absorption of the polymerized ionic liquids. Journal of Polymer Science, Part A: Polymer Chemistry, (2005), 43(7), 1432-1443.

College of Engineering and Applied Science