title: Drug-eluting scaffold to deliver chemotherapeutic medication for management of pancreatic cancer after surgery.
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.
authors.affiliation: Department of General Surgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Baiyong
authors.initials: B
authors.lastname: Shen
authors.forename: Xiaxing
authors.initials: X
authors.lastname: Deng
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Jiabin
authors.initials: J
authors.lastname: Jin
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D057139:Nanofibers / Q000737:chemistry; D036103:Nanotechnology; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: FOLFIRINOX; drug-eluting scaffold; electrospun scaffold; pancreatic cancer