Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases with a 5-year survival at a dismal 6% and with 80% of PDAC patients diagnosed at advanced incurable stages. The proposed Cancer Nanotechnology Platform Partnerships (CNPP) grant assembles a team of synthetic/materials chemist (Wenbin Lin, Ph.D.), surgical oncologist/cancer biologist (Jen Jen Yeh, M.D.), and pharmaceutical scientist/biophysicist (Leaf Huang, Ph.D.) to address the critical needs of delivering imaging probes for early diagnosis as well as promising chemotherapeutics for more effective treatment of PDAC. The three established UNC investigators with complementary expertise will take the challenge of developing sensitive diagnostic imaging modalities and effective therapies using targeted nanoparticle technology based on nanoscale metal-organic frameworks (NMOFs) that were recently developed in the Lin lab. NMOFs represent a unique class of hybrid nanomaterials with an ability to combine metal and organic components at a molecular level and to tune their structures and compositions in a modular fashion. The proposed NMOFs contain metal ions or complexes as the MRI imaging cargo and cisplatin or/and Gemcitabine prodrugs as the therapeutic cargoes. When linked to appropriate cell-targeting molecules, the NMOFs can be selectively and efficiently delivered to solid tumors to allow for early diagnosis and effective treatment of pancreatic cancer. To complement this basic science discovery, the Yeh lab has established novel mouse models of PDAC including orthotopic xenografts, the KRAS-driven genetically engineered mouse models (GEMMs), and patient-derived PDAC xenografts. These mouse models of PDAC provide a great opportunity for the testing of NMOFs as an effective delivery vehicle for imaging and chemotherapeutic agents in both primary and metastatic tumors of PDAC. We believe that the proposed research will lead to a new generation of hybrid nanomaterials for early detection and more effective therapy of PDAC, and thus providing new nanotechnology management strategies for cancer patients.

Public Health Relevance

The proposed research addresses the critical needs of early diagnosis and more effective treatment of PDAC. The new nanotechnology innovations are expected to have broad applicability across multiple tumor types and benefit a large number of cancer patients with different types of malignancies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA151455-03
Application #
8323985
Study Section
Special Emphasis Panel (ZCA1-SRLB-X (M1))
Program Officer
Grodzinski, Piotr
Project Start
2010-09-03
Project End
2013-06-30
Budget Start
2012-08-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$339,461
Indirect Cost
$145,267
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Duan, Xiaopin; Liu, Demin; Chan, Christina et al. (2015) Polymeric Micelle-Mediated Delivery of DNA-Targeting Organometallic Complexes for Resistant Ovarian Cancer Treatment. Small 11:3962-72
Chen, Yunching; Gao, Dong-Yu; Huang, Leaf (2015) In vivo delivery of miRNAs for cancer therapy: challenges and strategies. Adv Drug Deliv Rev 81:128-41
Chen, Gang; Liu, Di; He, Chunbai et al. (2015) Enzymatic synthesis of periodic DNA nanoribbons for intracellular pH sensing and gene silencing. J Am Chem Soc 137:3844-51
He, Chunbai; Liu, Demin; Lin, Wenbin (2015) Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer. Biomaterials 36:124-33
He, Chunbai; Chan, Christina; Weichselbaum, Ralph R et al. (2015) Nanomedicine for Combination Therapy of Cancer. EBioMedicine 2:366-7
Rocca, Joseph Della; Werner, Michael E; Kramer, Stephanie A et al. (2015) Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy. Nanomedicine 11:31-8
He, Chunbai; Lu, Jianqin; Lin, Wenbin (2015) Hybrid nanoparticles for combination therapy of cancer. J Control Release 219:224-36
Lu, Kuangda; He, Chunbai; Lin, Wenbin (2015) A Chlorin-Based Nanoscale Metal-Organic Framework for Photodynamic Therapy of Colon Cancers. J Am Chem Soc 137:7600-3
Poon, Christopher; He, Chunbai; Liu, Demin et al. (2015) Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer. J Control Release 201:90-9
He, Chunbai; Liu, Demin; Lin, Wenbin (2015) Nanomedicine Applications of Hybrid Nanomaterials Built from Metal-Ligand Coordination Bonds: Nanoscale Metal-Organic Frameworks and Nanoscale Coordination Polymers. Chem Rev 115:11079-108

Showing the most recent 10 out of 42 publications