Gadofullerene nanoparticles extend survival rate and down-regulate thrombin expression in orthotopic pancreatic cancer

Abstract

Pancreatic cancer is a devastating malignant disease with 5-year survival rate less than 8%. The impenetrable desmoplastic stroma of pancreatic tissue and serious side-effects of existing drugs hinder the effective treatment for pancreatic carcinoma. Thus, it is imperative to exploit much more safe and efficient methods to prolong the survival of pancreatic cancer patients. In this study, we explored a superior anti-pancreatic cancer strategy based on gadofullerene nanoparticles (GFNPs) using an orthotopic human pancreatic carcinoma (PANC-1) tumor model. It was demonstrated that GFNPs could efficiently suppress orthotopic pancreatic cancer in a dose manner, and significantly extend the survival rate of tumor-bearing mice. Of note, the proteomic profiling of tumor tissues revealed that GFNPs ameliorated the coagulation cascade dysfunction and down-regulated the thrombin expression in pancreatic tumor tissues. The regulation of abnormal thrombin by GFNPs was validated in vitro and in vivo. More importantly, GFNPs suppressed orthotopic pancreatic cancer with negligible adverse effects, superior to the widely recognized clinical anti-pancreatic cancer drug, gemcitabine. Together, this study provides a promising therapeutic for intractable pancreatic cancer as well as a potential to alleviate the cancer-associated thromboembolic diseases.