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 to develop materials that improve the T cell manufacturing process.
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. Nguyen, D.C.*, Song, K.*, Jokonya S., Yazdani, O., Sellers, D.L., Wang, Y., Zakaria, A., Pun, S.H. and Stayton P.S. Mannosylated STING agonist ‘drugamers’ for dendritic cell-mediated cancer immunotherapy. ACS Central Sci 2024, v10(3), 666-675.
2. Olshefsky, A., Benasutti, H., Sylvestre, M., Butterfield, G.L., Rocklin, G.J., Richardson, C., Hicks, D.R., Lajoie, M.J., Song, K., Leaf, E., Treichel, C., Decarreau, J., Ke, S., Kher, G., Carter, L., Chamberlain, J.S., Baker, D., King, N.P., and Pun, S.H. In vivo selection of synthetic nucleocapsids for tissue targeting. PNAS 2023, 120(46), e2306129120.
3. 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.
4. Lv, S.*, Sylvestre, M.*, Song, K., and Pun, S.H. Development of D-melittin polymeric nanoparticles for anti-cancer treatment. Biomaterials 2021, v277:121076.
5. Kacherovsky N*, Cardle II*, Cheng EL, Yu JL, Baldwin ML, Salipante SJ, Jensen MC, and Pun SH. Traceless aptamer-mediated isolation of CD8+ T cells for chimeric antigen receptor T-cell therapy. Nature Biomedical Engineering 2019, 3, 783-795.

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. Materials for Hemostasis

Image by William Walker

Traumatic injuries are the leading cause of death for the 1 to 46 age group in the United States.With Dr. Nathan White (UW Emergency Medicine), we are developing new biomaterials for treatment of trauma victim, including injectable hemostatic materials, multifunctional wound bandages, and low volume resuscitants. 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. Pichon T.J., Wang, X., Mickelson, E.E., Huang, W.C., Hilburg, S.L., Stucky, S., Ling, M., St. John, A.E., Ringgold, K.W., Snyder, J.M., Pozzo, L.D., Lu, M., White, N.J., and Pun S.H. Engineering low volume resuscitants for the prehospital care of severe hemorrhagic shock. Angew Chemie 2024, v63(31), e202402078.
2. 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.
3. Chan LWG, Wang X, Wei H, Pozzo LD, White NJ, and Pun SH. A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis. Sci. Transl. Med. 2015, 7, 277ra29.

We are grateful to NIH NHLBI for funding support.

3. 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.

4. 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 aptamer-mediated isolation of CD8+ T cells for chimeric antigen receptor T-cell therapy. Nature Biomedical Engineering 2019, 3, 783-795.

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