Drug-eluting scaffold to deliver chemotherapeutic medication for management of pancreatic cancer after surgery

Abstract

Qian Zhan,1 Baiyong Shen,1 Xiaxing Deng,1 Hao Chen,1 Jiabin Jin,1 Xing Zhang,2 Chenghong Peng,1 Hongwei Li1 1Department of General Surgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 2Department of Surgery, University of Chicago, Chicago, IL, USA Abstract: Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required. On the other hand, legitimate concerns have been raised about nanoparticle-mediated drug delivery because of its potential cytotoxicity. Therefore, we explored the local delivery of a reduced dosage of FOLFIRINOX, a four-drug regimen comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil, for pancreatic cancer using a biocompatible drug-eluting scaffold as a novel chemotherapy strategy after palliative surgery. In vitro assays showed that FOLFIRINOX in the scaffold caused massive apoptosis and thereby a decrease in the viability of pancreatic cancer cells, confirming the chemotherapeutic capability of the drug-eluting scaffold. In vivo studies in an orthotopic murine xenograft model demonstrated that the FOLFIRINOX in the scaffold had antitumorigenic and antimetastatic effects comparable with those achieved by intraperitoneal injection, despite the dose released by the scaffold being roughly two thirds lower. A mechanistic study attributed our results to the excellent ability of the FOLFIRINOX in the scaffold to destroy the CD133+CXCR4+ cell population responsible for pancreatic tumorigenesis and metastasis. This clinically oriented study gives rise to a promising alternative strategy for postsurgical management of pancreatic cancer, featuring a local chemotherapeutic effect with considerable attenuation of side effects. Keywords: electrospun scaffold, FOLFIRINOX, pancreatic cancer, drug-eluting scaffold