Research

Our research focuses on advancing macromolecule drug delivery technology by developing new materials. We are actively working in the following application areas:

1. Cancer Therapy

Over 12 million people in the United States are currently battling cancer. Cytotoxic chemotherapy remains the preferred frontline strategy used against most types of cancer. While effective, treatment-related side effects such as major organ damage, infertility, immunosuppression and nausea/vomiting severely compromise patient quality of life. We are developing technologies for improved detection and treatment of cancer.

Ongoing projects in this area include:

  1. Immunomodulation to potentiate chemotherapy. We are developing constructs for targeting tumor-associated macrophages (TAMs). The prevalence of these cells in tumor microenvironment has been shown to correlate with poor prognosis in patients. Using library selection, we have identified a peptide for targeting murine TAMs and an aptamer for targeting human monocyte/macrophage. We are developing targeted nano-formulations for that utilize macrophage delivery to increase inflammatory cytokine production in the tumor microenvironment as a means to improve outcome from standard treatments (in collaboration with Andrew Oberst, UW Immunology, Andre Lieber, UW Medical Genetics, Seth Masters and James Vince from the Walter and Eliza Hall Institute of Medical Research).
  2. Synthetic materials for T-cell engineering. T-cell immunotherapy is demonstrating remarking anti-cancer activity in several early clinical trials. We are working with Michael Jensen’s group (Seattle Children’s Research Institute) to develop materials that improve the process for T-cell manufacturing.
  3. Polymers for drug delivery. Current chemotherapies generally have a narrow therapeutic range. We are synthesizing polymeric drug carriers to change the biodistribution of small molecule drugs, thereby reducing toxicity.
  4. Cancer vaccine delivery. Cancer vaccines are a promising inmuno-oncology approach that can elicit anti-cancer protection from the immune system. Together with Patrick Stayton and Nora Disis, we are developing a polymer-based carrier that can be recognized by and activate dendritic cells for antigen presentation, leading to cancer prevention and therapy.
Selected recent publications:
  1. Lv, S.,* Sylvestre, M.,* Song, K., and Pun, S.H. Development of D-melittin polymeric nanoparticles for anti-cancer treatment. Biomaterials, accepted.
  2. Peeler, D.J.*, Yen, A*, Luera, N., Stayton, P.S., and Pun, S.H. Lytic polyplex vaccines enhance antigen-specific cytotoxic T cell response through induction of local cell death. Adv Therapeutics, accepted.
  3. Sylvestre M, Saxby C, Kacherovsky N, Gustafson HH, Salipante SJ, and Pun SH. Identification of a DNA aptamer that binds to human monocytes and macrophages. Bioconjugate Chem 2020, 31, 1899-1907.
  4. Kacherovsky N*, Cardle II*, Cheng EL, Yu JL, Baldwin ML, Salipante SJ, Jensen MC, and Pun SH. Traceless isolation of CD8+ T cells by reversible, aptamer-based selection for CAR T cell therapy. Nature Biomedical Engineering 2019, 3, 783-795.
  5. Olden BR*, Cheng Y*, Yu JL, and Pun SH. Cationic polymers for non-viral gene delivery to human T-cells. Journal of Controlled Release 2018, 282, 140-147.
  6. Cieslewicz M, Tang J, Yu JL, Cao H, Zavaljevski M, Motoyama K, Lieber A, Raines EW, and Pun SH. Targeted delivery of proapoptotic peptides to tumor-associated macrophages improves survival. Proceedings of the National Academy of Sciences 2013, 110, 15919-15924.

We are grateful to the following current and past funding sources: NIH NCI, NIH NIBIB, NSF DMR, Alliance for Cancer Gene Therapy, and Washington Research Foundation.

2. Delivery to the Central Nervous System

The delivery of exogenous agents to cells in the central nervous system is a powerful technique with applications in treatment of neurological disease.

Ongoing projects in this area include:

  1. Targeted drug delivery to glioma/glioblastoma cells. We are developing targeted polymers to deliver drugs to glioma and glioblastoma cells for brain cancer treatment (in collaboration with Jim Heath, Institute for Systems Biology, and Mark Davis, Caltech).
  2. Drug delivery for spinal cord injury. We are developing injectable and conducting materials for localized tissue repair after spinal cord injury (in collaboration with Philip Horner, Houston Methodist).
Selected recent publications:
  1. Peeler DJ, Luera N, Horner PJ, Pun SH, and Sellers DL. Polyplex transfection from intracerebroventricular delivery is not significantly affected by traumatic brain injury. Journal of Controlled Release 2020, 322, 149-156.
  2. Lee DC, Sellers DL, Liu F, Boydston AJ, and Pun SH. Synthesis of water-soluble anionic poly(cyclopentadienylene vinylene) from an insulating hydrophobic precursos and its use in conductive hydrogels. Angew Chemie 2020, 32, 13430-13436.
  3. Peeler DJ, Thai SN, Cheng YL, Horner PJ, Sellers DL, and Pun SH. pH-sensitive polymer micelles provide selective and potentiated lytic capacity to venom peptides for effective intracellular delivery. Biomaterials 2019, 192, 235-244.
  4. Zhao TY, Sellers DL, Cheng YL, Horner PJ, and Pun SH. Tunable, injectable hydrogels based on peptide-crosslinked, cyclized polymer nanoparticles for neural progenitor cell delivery. Biomacromolecules 2017, 18, 2723-2731.
  5. Sellers DL, Bergen JM, Johnson RN, Ravits J, Horner PH, and Pun SH. Targeted Axonal Import (TAxI) peptide delivers functional proteins into the spinal cord after peripheral administration. PNAS 2016, 113, 2514-2519.
  6. Sellers DL, Kim TH, Mount CW, Pun SH, and Horner PJ. Prolonged hirudin delivery from poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 and functional recovery from a demyelination lesion. Biomaterials 2014, 35, 8895-8902.

We are grateful to NIH NINDS, NIH NCI, and DOD SCIRP for funding support.

3. Materials for Hemostasis


Image by William Walker

Bleeding management is a critical part of care for trauma patients and those with bleeding disorders. Hemorrhage due to uncontrolled bleeding is responsible for 30-40% of deaths associated with traumatic injuries. With Dr. Nathan White (UW Emergency Medicine), we are developing new injectable hemostatic materials and multifunctional wound bandages. This work has been featured on the AAAS Science Update podcast and UWTV.

Selected recent publications:
  1. Lamm, R.J.,* Pichon, T.J.*, Huyan, F., Wang, X., Prossnitz, A.N. Manner, K., White, N.J., and Pun, S.H. Optimizing the polymer structure and synthesis method of PolySTAT, an injectable hemostat. ACS Biomaterials Sci Eng 2020, 6, 7011-7020.
  2. Lamm RJ, Lim EB, Weigandt KM, Pozzo LD, White NJ, and Pun SH. Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer. Biomaterials 2017, 132, 96-104.
  3. Chan LWG, Kim CH, Wang X, Pun SH, White NJ, and Kim TH. PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage. Acta Biomaterialia 2016, 31, 178-185.
  4. Chan LWG, Wang X, Wei H, Pozzo LD, White NJ, and Pun SH. Fibrin-crosslinking polymers for modulating clot properties and inducing hemostasis. Sci. Transl. Med. 2015, 7, 277ra29.

We are grateful to NIH NHLBI for funding support.

4. Kidney Disease Treatment

Chronic kidney disease is a major health problem worldwide. Due to limited therapies to arrest disease advancement to kidney failure, many patients suffer high morbidity and poor five-year survival rates. In many kidney diseases, injury and loss of kidney podocytes directly underlies declining kidney function. With Dr. Stuart Shankland (UW Nephrology), we are developing polymer-based materials for targeted drug delivery to the kidney.

Selected recent publications:
  1. Liu GW*, Pippin JW*, Eng DG, Lv S, Shankland SJ, and Pun SH. Nanoparticles exhibit greater accumulation in kidney glomeruli during experimental glomerular kidney disease. Physiological Rep 2020, 8, e14545.
  2. Cheng Y*, Liu GW*, Jain R, Pippin JW, Shankland SJ, and Pun SH. Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes. ACS Biomaterials Science and Engineering 2018, 4, 3968-3973.
  3. Liu GW*, Prossnitz AN*, Eng DG, Cheng Y, Subrahmanyam N, Pippin JW, Lamm RJ, Ngambenjawong C, Ghandehari H, Shankland SJ, and Pun SH. Glomerular disease augments kidney accumulation of synthetic anionic polymers. Biomaterials 2018, 178, 317-325.

We are grateful to the DOD PRMRP for funding support.

5. Aptamer discovery and engineering


Aptamers are oligonucleotide sequences capable of folding into secondary structures that bind with high affinities to target molecules. We are interested in the discovery of novel aptamers and the use of these aptamers for biomedical applications, ranging from cell manufacturing to targeted drug delivery to SARS-CoV-2 diagnostics.

Selected recent publications:
  1. Kacherovsky, N.,* Yang, L.F.,* Dang, H.V.,* Cheng, E.L., Cardle, I.I., Walls, A.C., McCallum, M., Sellers, D.L., DiMaio, F., Salipante, S.J., Corti, D., Veesler, D., † and Pun, S.H. † Discovery and characterization of spike N-terminal domain-binding aptamers for rapid SARS-CoV-2 S detection. Angew Chemie 2021, 133, 21381-21385
  2. Sylvestre M, Saxby C, Kacherovsky N, Gustafson HH, Salipante SJ, and Pun SH. Identification of a DNA aptamer that binds to human monocytes and macrophages. Bioconjugate Chem 2020, 31, 1899-1907.
  3. Kacherovsky N*, Cardle II*, Cheng EL, Yu JL, Baldwin ML, Salipante SJ, Jensen MC, and Pun SH. Traceless isolation of CD8+ T cells by reversible, aptamer-based selection for CAR T cell therapy. Nature Biomedical Engineering 2019, 3, 783-795.

We are grateful to the NIH NIAAA for funding support.