Nanoscale Metal-Organic Frameworks for Imaging and Therapy of Pancreatic Cancer
The University of North Carolina at Chapel Hill
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with a five-year survival at a dismal 6% and 80% of PDAC patients diagnosed at advanced incurable stages. The research team led by Drs. Lin and Yeh is addressing the critical needs of delivering imaging probes for early diagnosis as well as promising chemotherapeutics for more effective treatment of PDAC. The team is developing sensitive diagnostic imaging modalities and effective therapies using targeted nanoparticle technology based on nanoscale metal-organic frameworks (NMOFs) that were 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 and/or 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, 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.
This project aims to develop a new class of hybrid nanomaterials, namely, NMOFs, for early detection and more effective therapy of PDAC, and thus provide new nanotechnology management strategies for cancer patients.