Multiphysics and Multiscale Analysis for Chemotherapeutic Drug

Abstract

This paper presents a three-dimensional dynamic model for the chemotherapy design based on a multiphysics and multiscale approach. The model incorporates cancer cells, matrix degrading enzymes (MDEs) secreted by cancer cells, degrading extracellular matrix (ECM), and chemotherapeutic drug. Multiple mechanisms related to each component possible in chemotherapy are systematically integrated for high reliability of computational analysis of chemotherapy. Moreover, the fidelity of the estimated efficacy of chemotherapy is enhanced by atomic information associated with the diffusion characteristics of chemotherapeutic drug, which is obtained from atomic simulations. With the developed model, the invasion process of cancer cells in chemotherapy treatment is quantitatively investigated. The performed simulations suggest a substantial potential of the presented model for a reliable design technology of chemotherapy treatment.

Figure 1

Schematic drawing represents the process of cancer-cells invasion with chemotherapeutic drug.

Figure 2

Initial configurations of cancer cells and the ECM.

Figure 3

Evolution sequences of cancer-cells invasion with chemotherapy; matrix-degrading enzymes (MDEs) are secreted by cancer cells and chemotherapeutic drug particles surround cancer cells.

Figure 4

Mean-squared displacement (MSD) obtained from the trajectory of the drug molecules in MD simulation.

Figure 5

Number of cases in different ranges of diffusion coefficient.

Figure 6

(a) Diffusion of chemotherapeutic drug, (b) evolved concentration of chemotherapeutic drug in the treatment, and (c) distribution of chemotherapeutic drug in the diffusion process.

Figure 7

Morphological and the number changes of cancer cells (a) without chemotherapeutic drug and (b) with chemotherapeutic drug.

Figure 8

Reduction ratio of (a) cancer cells and (b) normal cells with various capacity of chemotherapeutic drug on destroying cells, η, at t = 2.0 × 10⁴.

Figure 9

(a) Velocities of cancer-cells migration with various concentrations of chemotherapeutic drug. The initial concentrations of drug are 0.0, 5.0 × 10⁻⁴, 1.0 × 10⁻³, and 5.0 × 10⁻³, respectively. (b) Position of cancer cells with different initial concentrations of drug. ξ = (Current volume of cancer cells/Initial volume of cancer cells) × 100%.