An interdisciplinary computational/experimental approach to evaluate drug-loaded gold nanoparticle tumor cytotoxicity

作者：Curtis Louis T; England Christopher G; Wu Min; Lowengrub John; Frieboes Hermann B^*

来源：Nanomedicine, 2016, 11(3): 197-216.

DOI：10.2217/nnm.15.195

• 3D cell culture
• cancer nanotherapy
• cancer simulation
• cisplatin
• gold nanoparticles
• lung cancer
• mathematical modeling
• NSCLC
• paclitaxel

Aim: 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. Materials & 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. Conclusion: Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy.

• 出版日期2016
• 单位西北大学