Integrated intravital microscopy and mathematical modeling to optimize nanotherapeutics delivery to tumors

Anne L. van de Ven, Min Wu, John Lowengrub, Steven Robert McDougall, Mark A. J. Chaplain, Vittorio Cristini, Mauro Ferrari, Hermann B. Frieboes

    Research output: Contribution to journalArticle

    69 Citations (Scopus)

    Abstract

    Inefficient vascularization hinders the optimal transport of cell nutrients, oxygen, and drugs to cancer cells in solid tumors. Gradients of these substances maintain a heterogeneous cell-scale microenvironment through which drugs and their carriers must travel, significantly limiting optimal drug exposure. In this study, we integrate intravital microscopy with a mathematical model of cancer to evaluate the behavior of nanoparticle-based drug delivery systems designed to circumvent biophysical barriers. We simulate the effect of doxorubicin delivered via porous 1000 × 400 nm plateloid silicon particles to a solid tumor characterized by a realistic vasculature, and vary the parameters to determine how much drug per particle and how many particles need to be released within the vasculature in order to achieve remission of the tumor. We envision that this work will contribute to the development of quantitative measures of nanoparticle design and drug loading in order to optimize cancer treatment via nanotherapeutics.
    Original languageEnglish
    Article number011208
    Pages (from-to)1-13
    Number of pages13
    JournalAIP Advances
    Volume2
    Issue number1
    DOIs
    Publication statusPublished - Jun 2012

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  • Cite this

    van de Ven, A. L., Wu, M., Lowengrub, J., McDougall, S. R., Chaplain, M. A. J., Cristini, V., Ferrari, M., & Frieboes, H. B. (2012). Integrated intravital microscopy and mathematical modeling to optimize nanotherapeutics delivery to tumors. AIP Advances, 2(1), 1-13. [011208]. https://doi.org/10.1063/1.3699060