|
|||||
|
|
Overcoming the stromal barrier for targeted delivery of HPMA copolymers to pancreatic tumors |
|
| Authors: | Brandon Buckway Yongjian Wang Abhijit Ray Hamidreza Ghandehari |
| Institution: | 1. Department of Pharmaceutics and Pharmaceutical Chemistry, and of Bioengineering, Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, 36 S Wasatch Dr, 5205 SMBB, Salt Lake City, UT 84112, USA;2. Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA;3. College of Life Sciences, Nankai University, Tianjin 300071, PR China;4. Synergetic Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;5. Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA |
| Abstract: | Delivery of macromolecules to pancreatic cancer is inhibited by a dense extracellular matrix composed of hyaluronic acid, smooth muscle actin and collagen fibers. Hyaluronic acid causes a high intratumoral fluidic pressure which prevents diffusion and penetration into the pancreatic tumor. This study involves the breaking down of hyaluronic acid by treating CAPAN-1 xenograft tumors in athymic nu/nu mice with targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers radiolabeled with 111In for single photon emission computerized tomography (SPECT) imaging. Two targeting strategies were investigated including αvβ3 integrin and HER2 receptors. HPMA copolymers were targeted to these receptors by conjugating short peptide ligands cRGDfK and KCCYSL to the side chains of the copolymer. Results demonstrate that tumor targeting can be achieved in vivo after treatment with hyaluronidase. This approach shows promise for enhanced delivery of polymer–peptide conjugates to solid tumors. |
| Keywords: | HPMA copolymer Pancreatic cancer HER2 Imaging Hyaluronidase Targeting |
| 本文献已被 ScienceDirect 等数据库收录！ | |