Mechanistic modeling identifies drug-uptake history as predictor of tumor drug resistance and nano-carrier-mediated response.

ABSTRACT: A quantitative understanding of the advantages of nanoparticle-based drug delivery vis-à-vis conventional free drug chemotherapy has yet to be established for cancer or other diseases despite numerous investigations. Here, we employ first-principles cell biophysics, drug pharmaco-kinetics, and drug pharmaco-dynamics to model the delivery of doxorubicin (DOX) to hepatocellular carcinoma (HCC) tumor cells and predict the resultant experimental cytotoxicity data. The fundamental, mechanistic hypothesis of our mathematical model is that the integrated history of drug uptake by the cells over time of exposure, which sets the cell death rate parameter, and the uptake rate are the sole determinants of the dose response relationship. A universal solution of the model equations is capable of predic

SUBMITTER: Pascal J 

PROVIDER: S-EPMC3891887 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature