Focal therapy of neuroblastoma using silk films to deliver kinase and chemotherapeutic agents in vivo

Acta Biomater. 2015 Jul;20:32-38. doi: 10.1016/j.actbio.2015.04.003. Epub 2015 Apr 8.

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.

Keywords: Chemotherapy; Controlled release; Neuroblastoma; Silk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Crizotinib
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems*
  • Female
  • Humans
  • Mice, Nude
  • Neuroblastoma / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Silk / chemistry*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Silk
  • Crizotinib
  • Doxorubicin