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

Nanomedicine
Louis T CurtisHermann B Frieboes

Abstract

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. 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. 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. Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy.

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Citations

Apr 23, 2016·Journal of Nanobiotechnology·Lee B SimsJill M Steinbach-Rankins
Aug 26, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Michael E HalwesHermann B Frieboes
Apr 11, 2017·Journal of Theoretical Biology·Pietro MascheroniBernhard A Schrefler
Feb 1, 2018·Journal for Immunotherapy of Cancer·Grace MahlbacherHermann B Frieboes
May 20, 2020·Scientific Reports·Ibrahim M ChamseddineMichael Kokkolaras
Oct 10, 2018·Annals of Biomedical Engineering·Hunter A Miller, Hermann B Frieboes
Apr 22, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Prashant DograZhihui Wang
Sep 26, 2020·Frontiers in Bioengineering and Biotechnology·Hermann B FrieboesBiana Godin
Mar 15, 2019·Pharmaceutical Research·Lee B SimsJill M Steinbach-Rankins
Jun 22, 2021·International Journal for Numerical Methods in Biomedical Engineering·Abhignyan NagesettiAnthony J McGoron

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Methods Mentioned

BETA
scanning electron microscopy
dynamic light scattering

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