title: Focal therapy of neuroblastoma using silk films to deliver kinase and chemotherapeutic agents in vivo.
abstract: Current methods for treatment of high-risk neuroblastoma patients include surgical intervention, in addition to systemic chemotherapy. However, only limited therapeutic tools are available to pediatric surgeons involved in neuroblastoma care, so the development of intraoperative treatment modalities is highly desirable. This study presents a silk film library generated for focal therapy of neuroblastoma; these films were loaded with either the chemotherapeutic agent doxorubicin or the targeted drug crizotinib. Drug release kinetics from the silk films were fine-tuned by changing the amount and physical crosslinking of silk; doxorubicin loaded films were further refined by applying a gold nanocoating. Doxorubicin-loaded, physically crosslinked silk films showed the best in vitro activity and superior in vivo activity in orthotopic neuroblastoma studies when compared to the doxorubicin-equivalent dose administered intravenously. Silk films were also suitable for delivery of the targeted drug crizotinib, as crizotinib-loaded silk films showed an extended release profile and an improved response both in vitro and in vivo when compared to freely diffusible crizotinib. These findings, when combined with prior in vivo data on silk, support a viable future for silk-based anticancer drug delivery systems.
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors: F Philipp
authors: FP
authors: Seib
authors: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors: Jeannine
authors: J
authors: Coburn
authors: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors: Ilona
authors: I
authors: Konrad
authors: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors: Nikolai
authors: N
authors: Klebanov
authors: Department of Biochemistry, Tufts University, Medford, MA, USA.
authors: Gregory T
authors: GT
authors: Jones
authors: Department of Surgery, Rush University Medical Center, Chicago, IL USA.
authors: Brian
authors: B
authors: Blackwood
authors: Department of Neurosurgery, Tufts Medical Center, Boston, MA, USA.
authors: Alain
authors: A
authors: Charest
authors: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors: David L
authors: DL
authors: Kaplan
authors: Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: bchiumd@uic.edu.
authors: Bill
authors: B
authors: Chiu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000077547:Crizotinib; D004317:Doxorubicin / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D047011:Silk / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D047011:Silk; D000077547:Crizotinib; D004317:Doxorubicin
keywords: Chemotherapy; Controlled release; Neuroblastoma; Silk