Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer. (October 2016)

• Record Type: Journal Article
• Authors: Zhang, Bo; Jiang, Ting; Shen, Shun; She, Xiaojian; Tuo, Yanyan; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo
• Is Part Of: Biomaterials. Volume 103(2016)
• Page Start: 12
• Page End: 21
• Publication Date: 2016-10
• Subjects: Cyclopamine -- Tumor extracellular matrix -- Nanotherapeutics -- Pancreatic cancer -- Hedgehog signaling pathway; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2016.06.048
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: The dense extracellular matrix in pancreatic ductal adenocarcinoma dramatically reduces the penetration and efficacy of nanotherapeutics. Disruption of the tumor extracellular matrix may help improve the distribution and efficacy of nanotherapeutics in pancreatic cancer. In this study, we tested whether cyclopamine, a special inhibitor of the hedgehog signaling pathway with powerful anti-fibrotic activity, could promote the penetration and efficacy of nanotherapeutics in pancreatic cancer. It was shown that cyclopamine disrupted tumor extracellular fibronectins, decompressed tumor blood vessels, and improved tumor perfusion. Furthermore, cyclopamine improved the accumulation and intratumoral distribution of i.v.-administered fluorescence indicator-labeled nanoparticles. Finally, cyclopamine also significantly improved the tumor growth inhibition effect of i.v.-injected nanotherapeutics in pancreatic tumor xenograft mouse models. Thus, cyclopamine may have great potential to improve the therapeutic effects of nanomedicine in patients with pancreatic cancer.