title: An interdisciplinary computational/experimental approach to evaluate drug-loaded gold nanoparticle tumor cytotoxicity.
abstract: OBJECTIVE
  Clinical translation of cancer nanotherapy has largely failed due to the infeasibility of optimizing the complex interaction of nano/drug/tumor/patient parameters. We develop an interdisciplinary approach modeling diffusive transport of drug-loaded gold nanoparticles in heterogeneously-vascularized tumors.
  
  
  METHODS
  Evaluated lung cancer cytotoxicity to paclitaxel/cisplatin using novel two-layer (hexadecanethiol/phosphatidylcholine) and three-layer (with high-density-lipoprotein) nanoparticles. Computer simulations calibrated to in-vitro data simulated nanotherapy of heterogeneously-vascularized tumors.
  
  
  RESULTS
  Evaluation of free-drug cytotoxicity between monolayer/spheroid cultures demonstrates a substantial differential, with increased resistance conferred by diffusive transport. Nanoparticles had significantly higher efficacy than free-drug. Simulations of nanotherapy demonstrate 9.5% (cisplatin) and 41.3% (paclitaxel) tumor radius decrease.
  
  
  CONCLUSIONS
  Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy.
authors.affiliation: Department of Bioengineering, University of Louisville, KY, USA.
authors.forename: Louis T
authors.initials: LT
authors.lastname: Curtis
authors.affiliation: Department of Pharmacology & Toxicology, University of Louisville, KY, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: England
authors.affiliation: Department of Engineering Sciences & Applied Mathematics, Northwestern University, Chicago, IL, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Mathematics, University of California, Irvine, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lowengrub
authors.affiliation: Department of Bioengineering, University of Louisville, KY, USA.|Department of Pharmacology & Toxicology, University of Louisville, KY, USA.|James Graham Brown Cancer Center, University of Louisville, KY, USA.
authors.forename: Hermann B
authors.initials: HB
authors.lastname: Frieboes
mesh_terms: D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*
chemical_list: D006046:Gold
keywords: 3D cell culture; NSCLC; cancer nanotherapy; cancer simulation; cisplatin; gold nanoparticles; lung cancer; mathematical modeling; paclitaxel
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