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

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

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    72 Citations (Scopus)


    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 x 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. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported License. []

    Original languageEnglish
    Article number011208
    Pages (from-to)-
    Number of pages13
    JournalAIP Advances
    Issue number1
    Publication statusPublished - Mar 2012

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