title: Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes.
abstract: For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers--polycaprolactone and poly(glycerol monostearate-co-caprolactone)--to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ∼90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection.
authors.affiliation: Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Medicine, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA.
authors.forename: Jonah A
authors.initials: JA
authors.lastname: Kaplan
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Medicine, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Freedman
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Padera
authors.affiliation: AcuityBio Corp., 200 Upland Rd., Newton, MA 02460, USA.
authors.forename: John
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA. Electronic address: ycolson@partners.org.
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
authors.affiliation: Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Medicine, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA. Electronic address: mgrin@bu.edu.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004337:Drug Carriers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D057139:Nanofibers; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D002945:Cisplatin
keywords: Drug delivery; Electrospinning; Lung cancer; Nanofibers; Superhydrophobic; Surgery