Evaluation of drug-loaded gold nanoparticle cytotoxicity as a function of tumor tissue heterogeneity.

cancer;biological modeling and simulation;nanotherapy;nanoparticle;chemotherapy;cisplatin

Hunter Allan Miller

University:University of Louisville

Department:Pharmacology and Toxicology

关键词: cancer;    biological modeling and simulation;    nanotherapy;    nanoparticle;    chemotherapy;    cisplatin;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=4177&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug strength affects the proportion of proliferating, hypoxic, and necrotic tissue fractions, which in turn dynamically affect and are affected by the vascular density. This study establishes a first step towards a more systematic methodology to assess the effect of vascular-induced tumor tissue heterogeneity on the response to nanotherapy.