Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment
Autor: | Alexander Zakharov, Andre Kajdacsy-Balla, Jennifer Poirier, Jamie Harris, Monika Pilichowska, Naohiko Ikegaki, Alexander V. Lyubimov, Jeannine M. Coburn, Bill Chiu, Hiroyuki Shimada, David L. Kaplan |
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Rok vydání: | 2016 |
Předmět: |
Drug
Cancer Research Vincristine medicine.medical_specialty medicine.medical_treatment media_common.quotation_subject Cell 02 engineering and technology 03 medical and health sciences 0302 clinical medicine Neuroblastoma Medicine Doxorubicin media_common Chemotherapy business.industry Large cell 021001 nanoscience & nanotechnology medicine.disease medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Immunology Cancer research Histopathology 0210 nano-technology business medicine.drug |
Zdroj: | International Journal of Cancer. 140:726-735 |
ISSN: | 0020-7136 |
Popis: | 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. |
Databáze: | OpenAIRE |
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