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. 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.
2. Polymers for drug delivery. With Patrick Stayton, we are synthesizing polymeric drug carriers to change the biodistribution of small molecule drugs for immunotherapy, thereby reducing toxicity.
3. 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.

1. Lv, S.*, Song, K.*, Yen, A., Peeler, D.J., Nguyen, D.C., Olshefsky, A., Sylvestre, M., Srinivasan, S., Stayton, P.S., and Pun, S.H. Well-defined mannosylated polymer for peptide vaccine delivery with enhanced antitumor immunity. Adv Healthcare Mat 2022, 11(9), 2101651.
2. Lv, S.*, Sylvestre, M.*, Song, K., and Pun, S.H. Development of D-melittin polymeric nanoparticles for anti-cancer treatment. Biomaterials 2021, v277:121076.
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.
4. 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 and aptamers for drug and gene delivery to the brain (in collaboration with Drew Sellers, UW Bioengineering).

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. 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.

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. This work is conducted as part of the RESCU (Resuscitation Engineering Science Unit) at the University of Washington.

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.

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.

1. Cheng, E.L.*, Cardle, I.I.*, Kacherovsky, N.*, Bansia, H.*, Wang, T.*, Zhou, Y-S., Raman, J., Yen, A.,Gutierrez, D., Salipante, S.J., des Georges, A., Jensen, M.C., and Pun, S.H. Discovery of a transferrin receptor 1-binding aptamer and its application in cancer cell depletion for adoptive T-cell therapy manufacturing. Journal of the American Chemical Society 2022, 144(30), 13851-13864
2. Yang, L.F., Kacherovsky, N., Liang, J., Salipante, S.J., and Pun, S.H. SCORe: SARS-CoV-2 Omicron variant RBD-binding DNA aptamer for multiplexed detection and pseudovirus neutralization. Analytical Chemistry 2022, 94(37), 12683-12690
3. 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
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.

We are grateful to the NIH NIBIB and NIAAA for funding support.