Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment.

Abstract

Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multicycle chemotherapies, resulting in short- and long-term toxicities. Here, we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment. The intratumoral drug concentration was significantly higher with intratumoral delivery versus IV. Furthermore, intratumor delivery decreased the maximum plasma concentration compared to IV delivery, reducing systemic exposure and possibly reduing long-term side effects of chemotherapy exposure. Histopathologically, tumors with remission periods >25 days before recurrence transformed from a "small-round-blue cell" (SBRC) to predominantly "large cell" neuroblastoma (LCN) histopathology, a more aggressive tumor subtype with unfavorable clinical outcomes. These results show that intratumoral chemotherapy delivery may be a treatment strategy for pediatric neuroblastoma, potentially translatable to other focal tumors types. Furthermore, this treatment modality allows for a clinically relevant mouse model of tumor transformation that may be used for studying the phenotypical tumor recurrence and developing more effective treatment strategies for recurrent tumors.

• Authors: Jeannine Coburn, Jamie Harris, Alexander D Zakharov, Jennifer Poirier, Naohiko Ikegaki, Andre Kajdacsy-Balla, Monika Pilichowska, Alexander V Lyubimov, Hiroyuki Shimada, David L Kaplan, Bill Chiu
• Journal: International journal of cancer (Int J Cancer) Vol. 140 Issue 3 Pg. 726-735 (Feb 01 2017) ISSN: 1097-0215 [Electronic] United States
• PMID: 27770551 (Publication Type: Journal Article)
• Copyright: © 2016 UICC.

Chemical References

• Antineoplastic Agents
• Delayed-Action Preparations
• Silk
• Vincristine
• Doxorubicin
• Fibroins

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Cell Line, Tumor
• Delayed-Action Preparations (administration & dosage)
• Disease Models, Animal
• Doxorubicin (administration & dosage)
• Drug Delivery Systems (methods)
• Fibroins (administration & dosage)
• Mice
• Neoplasm Recurrence, Local (drug therapy)
• Neuroblastoma (drug therapy)
• Silk (administration & dosage)
• Vincristine (administration & dosage)