An Interdisciplinary Computational/Experimental Approach to Evaluate Drug-Loaded Gold Nanoparticle Tumor Cytotoxicity

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-densitylipoprotein) nanoparticles. Computer simulations calibrated to in-vitro data simulated nanotherapy of heterogeneously-vascularized tumors. Results: Evaluation of freedrug 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.

Evaluating the influence of mechanical stress on anticancer treatments through a multiphase porous media model

“…This value is usually identified with the label IC 50 , for “half maximal inhibitory concentration” (Curtis et al, 2016). We find a value of ${\omega }_{\mathrm{italicenv}}^{ch}=1.185\times {10}^{-7}$, which we will denote from now on with IC 50 .…”

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

“…Moreover, the authors summarized the experimentally estimated coefficients with known literature data to complete the precise simulation of tumor nanotherapy response. 111 Two major advantages of the modeling of NPs' penetration into MCTS could be outlined. On one hand, it provides insight into the factors that affect the distribution of particles in avascular regions of tumors, and on the other hand, modeling helps to delineate the factors related to the improvement of the design of nanotherapeutic agents.…”

Thermal analysis in a triple-layered skin structure with embedded vasculature, tumor, and gold nanoshells

“…For hyperthermia cancer treatment, a recent advance is to inject golden nanoparticles into the tumor region in order to heat it up quickly [23][24][25][26][27][28][29][30][31][32][33][34][35][36]. Bayazitoglu and her colleagues [23][24][25] developed a model that used the finite difference time domain (FDTD) to calculate the heat distribution of nanoshells on a single layer of human biological tissue at varying particle distribution densities in different host mediums.…”

“…Liu et al [35] presented nanoscale optomechanical actuators for controlling mechanotransduction in living cells. Frieboes and Curtis et al [36] evaluated the effects of drugloaded gold nanoparticles in highly vascularized tumors, where the effect of the nanoparticles decreased tumor size in comparison to drug-free nanoparticles.…”