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

Research output: Contribution to journalArticle

73 Scopus citations

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 (US)
Article number011208
JournalAIP Advances
Volume2
Issue number1
DOIs
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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