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
Nanoparticle-based drug delivery vehicles are typically ~50-200 nm in size. These vehicles can achieve extended circulation in the body and can be modified to target specific tissues. However, delivery is not optimal due to transport limitations.
Ongoing projects in this area include:
- Immunomodulation to potentiate chemotherapy. We are developing targeted therapeutics to tumor-infiltrating leukocytes to modulate immune response to tumors (in collaboration with Elaine Raines, UW Pathology, and Andre Lieber, UW Medical Genetics).
- Early detection of esophageal cancer. We are developing targeted nanoparticles for fluorescent endoscopy applications (in collaboration with Joo Ha Hwang, UW Gastroenterology; William Grady, UW Gastroenterology and FHCRC; and Lih Lin, UW Electrical Engineering).
- Polymeric coatings for oncolytic adenovirus. We are synthesizing self-assembling materials for reversible shielding of oncolytic adenoviruses to reduce their immunogenicity and hepatotoxicity (in collaboration with Andre Lieber and Dmitry Shayakhmetov, UW Medical Genetics).
- Polymeric micelles for drug delivery. Current chemotherapies generally have a narrow therapeutic range. We are encapsulating drugs in polymeric micelles to change their biodistribution, thereby reducing toxicity.
- 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, accepted.
- Chan LW, Wang Y-N, Lin LY, Upton MP, Hwang JH, and Pun SH. Synthesis and characterization of anti-EGFR fluorescent nanoparticles for optical molecular imaging. Bioconjugate Chem. 2013, 24, 167-175.
- Kim TH, Mount CW, Dulken BW, Ramos J, Fu CJ, Khant HA, Chiu W, Gombotz W, and Pun SH. Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model. Mol. Pharm. 2012, 9, 135-143.
- Wang CH, Chan LW, Johnson RN, Chu DSH, Shi J, Schellinger JG, Lieber A, and Pun SH. HPMA-co-oligolysine copolymer-coated adenovirus transduce CAR-negative cells through interaction with sulfate proteoglycans. Biomaterials 2011, 3, 9536-9545.
We are grateful to 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, UW Neurosurgery).
- Targeted drug delivery to glioma cells. We are developing targeted polymers to deliver peptides and siRNA to glioma and glioblastoma cells for brain cancer treatment (in collaboration with Bob Rostomily, UW Neurosurgery).
- Drug delivery for spinal cord injury. We are developing injectable materials for localized drug delivery after spinal cord injury (in collaboration with Philip Horner, UW Neurosurgery).
- 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.
- Chu DSH, Johnson RN, and Pun SH. Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release. J. Control. Release 2012, 157, 445-454.
- 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. *Selected as Very Important Paper (VIP)
We are grateful to NIH NINDS for funding support.
3. Cell therapy and regenerative medicine
We are developing ex vivo and in vivo methods to manipulate cells of the immune system for therapy applications.
Specific projects include:
- Engineering monocyte-derived cells for anticalcification (in collaboration with Cecilia Giachelli, UW Bioengineering, and Tony Blau, UW Hematology).
- Identifying targeting ligands for sub-populations of activated macrophages (in collaboration with Elaine Raines, UW Pathology).
- Developing materials for T-cell immunotherapy (in collaboration with Michael Jensen, Seattle Children’s Hospital).
- Kacherovsky N, Harkey MA, Blau CA, Giachelli CM, and Pun SH. Combination of Sleeping Beauty transposition and Chemically Induced Dimerization selection for robust production of engineered cells. Nucleic Acids Res. 2012, 40, e85.
Funded by NIH NHLBI and Washington's Life Sciences Discovery Fund.