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:
- 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).
- 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.
- 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.
- 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.
- 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.
- Wang CE, Yumul RC, Lin J, Cheng Y, Lieber A, and Pun SH. Junction opener protein increases nanoparticle accumulation in epithelial solid tumors. Journal of Controlled Release 2018, 272, 9-16.
- Ngambenjawong C, Gustafson HH, Pineda JM, Cieslewicz ME, and Pun SH. Serum stability and affinity optimization of an M2 macrophage-targeting peptide (M2pep). Theranostics 2016, 6, 1403-1414.
- 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. PNAS 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:
- Gene delivery to the brain. We are synthesizing multifunctional polymers for targeted nucleic acid delivery to neural progenitor cells in the subventricular zone of the brain (in collaboration with Philip Horner, Houston Methodist).
- 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).
- 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).
- 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.
- 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.
- 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.
- 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.
- Wei H, Volpatti LR, Sellers DL, Maris DO, Andrews IW, Hemphill AS, Chan LW, Chu DS, Horner PJ, and Pun SH. Dual-responsive, stabilized nanoparticles for efficient in vivo plasmid delivery. Angew. Chem. Int. Ed. Engl. 2013, 52, 5377-5381.
- Wei H, Schellinger JG, Chu DSH, and Pun SH. Neuron-targeted copolymers with sheddable shielding blocks synthesized using a reducible, RAFT-ATRP double-head agent. J. Am. Chem. Soc. 2012, 134, 16554-16557.
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:
- 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.
- 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.
- 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- and cell-based therapies to protect and regenerate podocytes.Selected recent publications:
- 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.
- 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 support.