Research Themes:
Instrumentation, Imaging and Image-Guided Therapy
Biomaterials and Regenerative Medicine
Molecular and Cellular Engineering

Education

PhD (chemical engineering), California Institute of Technology, 2000
MS (chemical engineering), California Institute of Technology, 1998
BS (chemical engineering), Stanford University, 1996

Research Interests

• Non-viral gene delivery
• Delivery of drugs and molecular contrast agents
• Intracellular trafficking

Contact Information

Department of Bioengineering
University of Washington
Box 355061
William H. Foege Building, Room N530P
Phone: 206-685-3488
Fax: 206-543-6124
E-mail
Web site: http://faculty.washington.edu/spun

Research Description

Many current drug delivery designs have made significant improvements in overcoming extracellular barriers (e.g., stability of vehicles, increased circulation in vivo, optimal tissue targeting and delivery). However, the trafficking of delivered material after cellular uptake often remains inefficient. Understanding and overcoming the limitations in intracellular trafficking would therefore have broad applications in the field of drug delivery.

Our research is focused on accomplishing efficient, tissue- and/or organelle-specific delivery of macromolecules and molecular contrast agents.  Specific on-going projects in the laboratory include the development of delivery vehicles (i) for neuron-targeted gene and siRNA delivery for potential treatment of neurodegenerative diseases, (ii) with improved penetration and efficacy for treatment of solid tumors, (iii) immobilized on solid surfaces or integrated with biocompatible scaffolds for tissue engineering applications and (iv) that can be applied to improve tumor targeting of molecular imaging agents.

Honors & Awards

• 2008: Junior Faculty Innovator Award, UW College of Engineering
• 2008: Undergraduate Mentor Award, University of Washington
• 2007: Outstanding Teacher/Mentor Award, UW Bioengineering
• 2006: Presidential Early Career Award for Scientists and Engineers (PECASE)
• 2005: NSF CAREER Award
• 2004: National Hemophilia Foundation Career Development Award
• 2004: Marian E. Smith Jr. Faculty Research Award, UW
• 2002: MIT's Technology Review: "Top 100 Young Innovators"

Selected Publications

Design and evaluation of non-viral gene delivery systems to overcome trafficking barriers

• Kwon, E.J., Bergen, J.M. and Pun, S.H. (2008) Application of an HIV gp41-derived peptide for enhanced intracellular trafficking of synthetic gene and siRNA delivery vehicles. Bioconjugate Chemistry, 19(4):920-927.
• Saul, J.M.,* Wang, C.K.,* Ng, C.P., and Pun, S.H. (2008) Multilayer nanocomplexes of polymer and DNA exhibit enhanced gene delivery Advanced Materials, 20(1):19-25.
• Burke, R.S. and Pun, S.H. (2008) Extracellular barriers to in vivo PEI and PEGylated PEI polyplex-mediated gene delivery to liver. Bioconjugate Chemistry 19(3):693-704.

Neuron-targeted gene delivery

• Kwon, E.J., Bergen, J.M., Park, I.K., and Pun, S.H. Peptide-modified vectors for nucleic acid delivery to neurons. J Controlled Rel, accepted.
• Bergen, J.M. and Pun, S.H. (2008) Analysis of intracellular barriers encountered by non-viral gene carriers in a model of spatially-controlled delivery to neurons. Journal of Gene Medicine 10(2):187-197.
• Bergen, J.M., Park, I.K., Horner, P.J., and Pun, S.H. (2008) Nonviral approaches for neuronal delivery of nucleic acids. Pharmaceutical Research, 25(5):983-998.
• Park, I.K., Lasiene, J., Chou, S.H., Horner, P.J., and Pun, S.H. (2007) Neuron-specific delivery of nucleic acids mediated by Tet1-modified poly(ethylenimine). Journal of Gene Medicine 9:691-702.

Gene delivery to 3-D culture systems

• Ng, C.P., Goodman, T.T., Park, I.K. and Pun, S.H. (2009) Bio-mimetic surface engineering of plasmid-loaded nanoparticles for active intracellular trafficking by actin "comet tail" motility. Biomaterials, accepted.
• Goodman, T.T., Ng, C.P., and Pun, S.H. 3-D tissue culture systems for the evaluation and optimization of nanoparticle-based drug carriers. Bioconj Chem, 19:1951-1959.
• Ng, C.P. and Pun, S.H. (2008) A versatile 3-D soft tissue perfusion chamber for mimicking tissue microenvironments. Biotechnology and Bioengineering 99(6):1490-1501.
• Goodman, T.T., Chen, J., Matveev, K., and Pun, S.H. (2008) Spatio-temporal modeling of nanoparticle delivery to multicellular spheroids. Biotechnology and Bioengineering, 101(2):388-399.
• Goodman, T.T., Olive, P.L., Pun, S.H. (2007) Increased nanoparticle penetration in collagenase-treated multicellular spheroids. International Journal of Nanomedicine 2(2):265-274.

Tissue engineering applications of gene therapy

• Saul, J.M., Linnes, M.P., Ratner, B.D., Giachelli, C.M., and Pun, S.H. (2007) Delivery of non-viral gene carriers from sphere-templated fibrin scaffolds for sustained transgene expression Biomaterials 28(31):4705-4716.
• Park, I.K., von Recum, H.A., Jiang, S., and Pun, S.H. (2006) Supramolecular assembly of cyclodextrin-based nanoparticles on solid surfaces for gene delivery. Langmuir 22:8478-8484.

Development of molecular imaging formulations for in vivo applications

• Park, I.K., Ng, C.P., Wang, J., Chu, B.C., Wang, C., Zhang, S.R., and Pun, S.H. (2008) Determination of nanoparticle vehicle unpackaging by MR imaging of a T2 magnetic relaxation switch. Biomaterials 29(6): 724-732.
• Rodriguez, V.,* Henry, S.,* Hoffman, A.S., Stayton, P.S., Li, X., and Pun, S.H. (2008) Polymeric micelle encapsulation of indocyanine green. Journal of Biomedical Optics, 13(1), Article 014025.