Louis T Curtis1, Christopher G England2, Min Wu3, John Lowengrub4, Hermann B Frieboes1,2,5. 1. Department of Bioengineering, University of Louisville, KY, USA. 2. Department of Pharmacology & Toxicology, University of Louisville, KY, USA. 3. Department of Engineering Sciences & Applied Mathematics, Northwestern University, Chicago, IL, USA. 4. Department of Mathematics, University of California, Irvine, CA, USA. 5. James Graham Brown Cancer Center, University of Louisville, KY, USA.
Abstract
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.
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 cancercytotoxicity 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.
Entities:
Keywords:
3D cell culture; NSCLC; cancer nanotherapy; cancer simulation; cisplatin; gold nanoparticles; lung cancer; mathematical modeling; paclitaxel
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