Objectif
"Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. While the enhanced permeability and retention effect has served as a key rationale for using nanoparticles to treat solid tumors, it does not enable uniform delivery of these particles to all regions of tumors in sufficient quantities. This heterogeneous distribution of therapeutics is a result of physiological barriers presented by the abnormal tumor vasculature and interstitial matrix. These barriers are in large part responsible for the modest survival benefit offered in many cases by clinically approved nanotherapeutics and must be overcome to realize the promise of nanomedicine in patients. More specifically, we need to determine the design criteria - the size, charge and configuration of various nanoparticle platforms - that optimize drug delivery to tumors. Here, I propose the development of a mathematical framework for the delivery of therapeutic nanoparticles to solid tumors. The model will account directly for the properties of the tumor micro-environment as well as for the properties (size, charge and configuration) of nanoparticles to predict their intratumoral distribution. I will specify the model to a human sarcoma and a human mammary carcinoma cell line for which a complete set of experimental data that characterize their micro-environment exists. Informed by these experimental measurements, I will use the mathematical model to construct ""design maps"" that will predict the nanoparticle properties that optimize intratumoral delivery, and thus the efficacy of cancer therapy. I will also employ the model to investigate if modifications in the tumor micro-environment with the use of anti-angiogenic and anti-fibrotic agents can improve the distribution of nanomedicine to solid tumors."
Champ scientifique
Appel à propositions
FP7-PEOPLE-2010-RG
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Régime de financement
MC-IRG - International Re-integration Grants (IRG)Coordinateur
1678 Nicosia
Chypre