Enhancing the efficacy of drug-loaded nanocarriers against brain tumors by targeted radiation therapy

Brian C. Baumann, Gary D. Kao, Abdullah Mahmud, Takamasa Harada, Joe Swift, Christina Chapman, Xiangsheng Xu, Dennis E. Discher, Jay F. Dorsey

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Glioblastoma multiforme (GBM) is a common, usually lethal disease with a median survival of only ~15 months. It has proven resistant in clinical trials to chemotherapeutic agents such as paclitaxel that are highly effective in vitro, presumably because of impaired drug delivery across the tumor's blood-brain barrier (BBB). In an effort to increase paclitaxel delivery across the tumor BBB, we linked the drug to a novel filomicelle nanocarrier made with biodegradable poly(ethyleneglycol)- block-poly(e-caprolactone-r-D,L-lactide) and used precisely collimated radiation therapy (RT) to disrupt the tumor BBB's permeability in an orthotopic mouse model of GBM. Using a non-invasive bioluminescent imaging technique to assess tumor burden and response to therapy in our model, we demonstrated that the drugloaded nanocarrier (DLN) alone was ineffective against stereotactically implanted intracranial tumors yet was highly effective against GBM cells in culture and in tumors implanted into the flanks of mice. When targeted cranial RT was used to modulate the tumor BBB, the paclitaxel-loaded nanocarriers became effective against the intracranial tumors. Focused cranial RT improved DLN delivery into the intracranial tumors, significantly improving therapeutic outcomes. Tumor growth was delayed or halted, and survival was extended by >50% (p
    Original languageEnglish
    Pages (from-to)64-79
    Number of pages15
    JournalOncotarget
    Volume4
    Issue number1
    Publication statusPublished - 2013

    Keywords

    • Brain tumors
    • Chemotherapy
    • Glioblastoma multiforme
    • Nanocarrier
    • Radiation therapy

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